Quarterly Drug Pipeline: April 2024

Clinical insights and competitive intelligence on anticipated drugs in development

Drug Pipeline

Clinical insights and competitive intelligence on anticipated drugs in development

Editor-in-chief's message

Welcome to the Prime Quarterly Drug Pipeline! Dive into clinical insights and competitive intelligence on anticipated drugs in development, so you are well-sourced on the drug pipeline.

Methodology

The Quarterly Drug Pipeline is complex and fluid. Our talented and committed team of clinical and analytics experts are excited to bring you this robust publication after thoughtful research. Specialty and traditional drugs that are covered under the pharmacy and medical benefits are featured. New molecular entities, pertinent new and expanded indications for existing medications, biosimilars and regenerative medicines, such as gene and cellular therapies, are also profiled.

Quarterly Drug Pipeline details both agents submitted for United States (U.S) Food and Drug Administration (FDA) review and those in phase 3 study with a likelihood to apply to the FDA. Our Deep Dives consider the evidence, the products’ potential to fill an unmet need or become the new standard of care, and the ability to replace existing therapies.

A market agnostic financial forecast primarily from Evaluate™ is included for select agents to assist payers with assessing the potential budgetary impact of the pipeline. Five-year projected annual U.S. sales are forecasted.

Reflection

Thus far in 2024, the agency has approved 11 novel drugs which is on par with the number of approvals about the same time last year. Of note, most of the approvals so far in 2024 use at least one of the FDA’s expedited approval programs. Some of the noteworthy approvals include a new agent for NASH, a new indication for Wegovy® for secondary CVD prevention in obesity/overweight, a new option for Duchene muscular dystrophy and a new medication for pulmonary arterial hypertension. While numbers do not tell the entire story, they do represent significant innovation in patient care and advance public health for the American public.

On the horizon

The FDA decisions for specialty medications (78%) and for orphan drugs (32%) continue to grow for agents with applications submitted to the FDA. Two agents are seeking FDA’s Accelerated Approval.

Notable anticipated approvals for second quarter 2024 include:

A gene therapy for a rare disease
First biologic for COPD
First biosimilar to intravitreal Eylea®
First-in-class oncology agent for SCLC
First RSV vaccine using the mRNA platform

We hope you enjoy the report!

Maryam Tabatabai
Vice President, Clinical Information

Editorial team

Maryam Tabatabai
Editor-In-Chief
Vice President, Clinical Information

Carole Kerzic, RPh
Executive Editor
Clinical Pharmacist, Drug Information

Nicole Kjesbo, PharmD, BCPS
Executive Editor
Clinical Program Direcotr, Pipeline

Andrea Henry, PharmD, MBA, BCPS
Specialty Drug Information Pharmacist

Katie Lockhart
Senior Manager, Analytics

Olivia Pane, PharmD, CDCES
Clinical Pharmacist, Drug Information

Michelle E. Pannone-Booth, PharmD
Senior Director, Clinical Account Services

The drug pipeline is fluid; the dates and information within this publication are subject to change. Nothing herein is or shall be construed as a promise or representation regarding past or future events and Prime Therapeutics expressly disclaims any and all liability relating to the use of or reliance on the information contained in this presentation. The information contained in this publication is intended for educational purposes only and should not be considered clinical, financial, or legal advice. By receipt of this publication, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced, distributed to, or disclosed to others at any time without the prior written consent of Prime Therapeutics.

Deep dive

The Deep Dive section features an analysis for select pipeline drugs that are expected to be FDA-approved in the upcoming quarters. Selected agents are expected to have a high clinical and/or financial impact on healthcare. Agent selection considers the evidence — the products’ potential to fill an unmet need, become the new standard of care, or the ability to replace existing therapies. Typically, Deep Dives focus on new moieties, however, existing drugs that may offer a novel mechanism for existing conditions may be featured. Agents granted designations from the FDA to expedite review and/or support development and evaluation of pipeline drugs are also considered.

Specialty drug names appear in magenta throughout the publication.

afamitresgene autoleucel IV

Manufacturer: Adaptimmune

Proposed indications

Advanced synovial sarcoma

Clinical overview

Mechanism of action
Afamitresgene autoleucel (afami-cel) is an autologous T-cell therapy transduced via a lentiviral vector to express a high-affinity and specific T-cell receptor that targets melanoma-associated antigen A4 (MAGE-A4) peptides expressed along with human leukocyte antigen-A2 (HLA-A2) on the tumor cell surface.

Clinical trials
Afami-cel is being evaluated in the ongoing, open-label, single-arm, phase 2 SPEARHEAD-1 trial (NCT04044768) in patients with metastatic or inoperable advanced synovial sarcoma. Enrolled patients are 16 to 75 years of age (10 years of age at select sites) and have tumors that are HLA-A*02 and MAGE-A4 positive. Patients received previous treatment with an anthracycline agent or ifosfamide, with a median of three prior lines of systemic therapy (range, 1 to 12). An interim analysis reported an overall response rate (ORR) of approximately 39% (primary endpoint) and a median duration of response (DOR) of about 12 months. The median overall survival (OS) with afami-cel was higher compared to the historical OS in patients who received ≥ two prior lines of therapy (approximately 17 months versus < 12 months, respectively), and 70% of patients were alive two years after receiving afami-cel. Treatment-emergent adverse events (TEAEs) with afami-cel included cytokine release syndrome (CRS) and hematologic toxicities.

Dosage and administration
Afami-cel is administered via IV infusion as a single dose of 1 x 109 to 10 x 109 transduced T cells after receiving lymphodepleting chemotherapy (cyclophosphamide and fludarabine).

Place in therapy

Synovial sarcoma is a rare soft tissue sarcoma (STS), with about 800 to 1,000 new cases occurring each year in the U.S. It is a mesenchymal tumor caused by translocation between chromosomes X and 18 that results in the expression of several SS18-SSX fusion proteins. Synovial sarcoma is primarily diagnosed in adolescents and adults < 30 years of age. It can occur anywhere in the body but usually develops near joints in the extremities (hip, knee, ankle and shoulder). Synovial sarcoma is an aggressive tumor with a high likelihood for metastasis. The overall five-year survival rate is estimated between 36% to 76%, and depends on tumor size, location and tumor spread.

Surgical resection with radiation therapy is the standard of care (SOC) for localized synovial sarcoma. Neoadjuvant or adjuvant chemotherapy (anthracycline-based regimen ± ifosfamide) is also used and is associated with an estimated response rate of 25% to 60%. Certain tyrosine kinase inhibitors are recommended in the presence of NTRK gene mutation (larotrectinib [Vitrakvi®], entrectinib [Rozelytrek®]) or in the advanced or metastatic setting (pazopanib [Votrient®]).

MAGE-A4 is present in up to 82% of synovial sarcoma tumors and is not expressed in normal tissue, making it a potential target for treatment. Afami-cel is a first-in-class T-cell receptor T-cell therapy directed at MAGE-A4 and has demonstrated benefit in treating advanced cases. If approved, it may prove to be an important treatment for patients with advanced synovial sarcoma, a population with poor prognosis and limited options.

FDA approval timeline

August 4, 2024

FDA designations: Orphan Drug, Priority Review, RMAT

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected annual U.S. sales	$3	$9	$15	$20	$26

Dupixent® (dupilumab) SC

Manufacturer: Sanofi/Regeneron

Proposed indications

Uncontrolled chronic obstructive pulmonary disease (COPD) as add-on maintenance therapy.

Clinical overview

Mechanism of action
Dupixent® is a human monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling.

Clinical trials
The randomized, double-blind, 52-week, phase 3 BOREAS trial (NCT03930732; n=939) evaluated the safety and efficacy of Dupixent in adults with COPD and evidence of type 2 inflammation (eosinophil count ≥ 300 cells/µL). COPD was uncontrolled despite triple therapy (ICS + LABA + LAMA). Eligible patients were 40 to 80 years of age, current or former tobacco smokers with a smoking history of ≥ 10 pack-years and did not have a current or past diagnosis of asthma. In the trial, Dupixent led to a significant 30% reduction in the primary endpoint of annualized rate of moderate or severe COPD exacerbations compared to placebo (0.78 versus 1.1, respectively; rate ratio, 0.7; p<0.001). Per the study protocol, moderate exacerbations required treatment with a systemic glucocorticoid and/or an antibiotic agent, and severe exacerbations led to hospitalization, emergency medical care or death. Topline data from the replicate, phase 3 NOTUS study (NCT04456673, n=935; 40 to 85 years of age) confirmed the results of the BOREAS trial and reported a 34% reduction in annualized rate of moderate or severe COPD exacerbations at 52 weeks (p=0.0002) with Dupixent compared to placebo. In addition, in both trials, secondary endpoints showed significant improvements in lung function (FEV1) by week 12 that were sustained through week 52. Both trials reported a safety profile with Dupixent similar to its other approved indications. Common TEAEs reported were back pain, COVID-19, diarrhea, headache and nasopharyngitis.

Dosage and administration
In both trials, Dupixent was administered subcutaneously (SC) at a dose of 300 mg every two weeks.

Place in therapy

An estimated 14.2 million (6.5%) people are diagnosed with COPD in the U.S., where it is a leading cause of death. COPD is a complex, chronic inflammatory airway disease characterized by respiratory symptoms (e.g., dyspnea, cough, sputum production and/or exacerbations) due to airway (bronchitis/bronchiolitis) and/or alveoli (emphysema) abnormalities that cause persistent, often progressive, airflow obstruction. A key risk factor for developing COPD is long-term exposure to toxic substances, such as tobacco smoke.

Type 2 inflammation is found in patients with asthma, and there is growing evidence that it is present in 20% to 40% of patients with COPD. The cytokines IL-4, IL-5 and IL-13 play a key role in type 2 inflammation by promoting the activation and trafficking of type 2 inflammatory cells, including eosinophils, in the lungs. Type 2 inflammation may increase the risk of COPD exacerbation, although evidence is mixed. Moreover, tobacco smoking has been shown to increase the production of pro-inflammatory cytokines (e.g., IL-4, IL-8, TNF-α) and may lead to a decreased response to inhaled corticosteroids, which is recommended as an add-on therapy in patients with severe COPD with a history of exacerbations.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends triple therapy with a LABA + LAMA + ICS for patients who have experienced ≥ 2 moderate exacerbations or ≥ 1 exacerbation leading to hospitalization if the blood eosinophil count is ≥ 300 cells/µL. For patients who experience a COPD exacerbation while on triple therapy, the addition of the oral PDE4 inhibitor Daliresp (roflumilast) (in patients with FEV1 < 50% predicted and chronic bronchitis) or the macrolide antibiotic azithromycin (for current non-smokers) may be considered.

Dupixent inhibits IL-4 and IL-13 signaling and thereby decreases type 2 inflammation. In phase 3 trials, when added to background triple therapy, Dupixent led to a significant reduction in moderate to severe COPD exacerbations in patients who were current or past smokers and had an elevated blood eosinophil level (≥ 300 cells/µL). If approved, this SC injectable agent will be the first biologic therapy indicated for COPD and could compete with Daliresp® as an add-on to triple therapy. Ensifentrine, an inhaled dual PDE3 and PDE4 inhibitor by Verona Pharma, has also been submitted for maintenance therapy in patients with moderate to severe COPD; an FDA decision is expected in late June 2024.

Dupixent is also approved for several other indications including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE) and prurigo nodularis (PN).

FDA approval timeline

June 27, 2024

FDA designations: Breakthrough Therapy, Priority Review

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales *reported for COPD only*	$0	$49	$100	$152	$203

elafibranor oral

Manufacturer: Genfit / Ipsen

Proposed indications

Primary biliary cholangitis (PBC)

Clinical overview

Mechanism of action

Elafibranor is a dual peroxisome proliferator-activated receptor alpha and delta (PPAR-α/δ) agonist

Clinical trials
The randomized (2:1), double-blind, placebo-controlled phase 3 ELATIVE trial (NCT04526665) evaluated the efficacy and safety of elafibranor in 161 patients with PBC who had an inadequate response to ursodeoxycholic acid (UDCA). The primary endpoint was a biochemical response (defined as an alkaline phosphatase [ALP] level of < 1.67 × ULN, with a reduction of ≥ 15% from baseline, and normal total bilirubin levels) at week 52. This was achieved in 51% of patients who received elafibranor compared to 4% who received placebo (difference, 47%; p<0.001). There was no significant difference in resolution of moderate to severe pruritus between the groups. The most common TEAEs (≥ 10%) were abdominal pain, diarrhea, nausea and vomiting.

Dosage and administration

In the clinical trial, elafibranor 80 mg was administered orally once daily.

FDA approval timeline

June 10, 2024

FDA designations: Breakthrough Therapy, Orphan Drug, Priority Review

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$8	$30	$57	$77	$99

seladelpar oral

Manufacturer: Cymabay

Proposed indications

Chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy

Clinical overview

Mechanism of action

Axatilimab is a monoclonal antibody targeting the colony stimulating factor 1 receptor (CSF-1R), which is expressed on monocytes and macrophages and is activated through its ligands, IL-34 and CSF-1.

Clinical trials
The randomized, open-label, phase 2 AGAVE-201 (NCT04710576) trial evaluated axatilimab in 241 allogeneic HCT recipients with recurrent or refractory cGVHD. Patients were randomized to one of three doses of axatilimab. The primary endpoint of ORR at 24 weeks (6 cycles) was 74% with 0.3 mg/kg every 2 weeks, 67% with 1 mg/kg every 2 weeks and 50% with 3 mg/kg every 4 weeks; complete response rates were 1%, 0% and 1%, respectively. In addition, 60%, 60% and 53% of patients in the respective cohorts maintaining response at 12 months. The most frequent grade ≥ 3 TEAEs reported were infection or infestations, elevated blood creatine phosphokinase and pneumonia.

Dosage and administration

In the clinical trial, axatilimab was administered IV every 2 weeks at doses of 0.3 mg/kg or 1 mg/kg, or 3 mg/kg every 4 weeks.

Place in therapy

Chronic GVHD is a complication of allogenic HCT in which the transplanted cells attack host cells resulting in inflammation and fibrosis. Chronic GVHD can be life-threatening, affecting multiple organ systems. It is characterized by fibrosis and various clinical features like autoimmune disorders. It is estimated to occur in approximately 30% to 50% of allogenic HCT recipients. Typically, cGVHD develops within the first year after HCT, but can be present many years later.

High-dose corticosteroids are the standard first-line treatment for cGVHD, with response observed in about 50% of patients; however, more than half of patients will require second-line therapy within 2 years. The kinase inhibitors, ruxolitinib (Jakafi®; preferred), belumosudil (Rezurock®), and ibrutinib (Imbruvica®) are approved to treat cGVHD as second or later line therapy. Many other agents have been used off-label depending on organ involvement and include imatinib (Gleevec®), abatacept (Orencia®), alemtuzumab (Campath®, Lemtrada®), calcineurin inhibitors (cyclosporine, tacrolimus), etanercept (Enbrel®), hydroxychloroquine, interleukin-2, low-dose methotrexate, mTOR inhibitors, mycophenolate mofetil, pentostatin and rituximab (Rituxan® or biosimilars).

CSF-1R–dependent monocytes play a key role in profibrotic (M2) macrophage differentiation, polarization, and function and promote sustained inflammation and tissue injury during cGVHD. In addition, these cells accelerate maladaptive tissue repair and fibrosis. If approved, axatilimab will provide a new mechanism in combating cGVHD, a disorder that continues to have unmet medical need.

FDA approval timeline

August 28, 2024

FDA designations: Fast Track, Orphan Drug, Priority Review

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$12	$114	$220	$364	$533

imetelstat IV

Manufacturer: Geron

Proposed indications

Transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (MDS) who have failed to respond to, have lost response to, or are ineligible for erythropoiesis-stimulating agents (ESAs)

Clinical overview

Mechanism of action
Imetelstat is a telomerase inhibitor. It selectively targets malignant hematopoietic stem and progenitor cells with high telomerase activity by direct binding to the RNA template, resulting in malignant cell apoptosis and potential disease-modifying activity.

Clinical trials
The randomized, double-blind, placebo-controlled, phase 3 IMerge trial (NCT02598661) evaluated imetelstat in 178 adults with RBC transfusion-dependent, low- or intermediate-risk MDS that was relapsed, refractory to, or ineligible for ESA therapy. Patients had not received prior treatment with azacitidine, decitabine, or lenalidomide. The median follow-up was 19.5 months in the imetelstat group and 17.5 months in the placebo group. The study demonstrated that significantly more patients treated with imetelstat achieved the primary endpoint of RBC transfusion independence in ≥ 8 weeks compared to those who were given placebo (40% versus 15%, respectively; p=0.0008). In addition, 28% and 13.6% of patients treated with imetelstat remained RBC transfusion-independent at ≥ 24 weeks and ≥ 1 year, respectively, compared to 3.3% and 1.7%, respectively, in those who received placebo. Grade 3 to 4 TEAEs occurred in 91% of patients in the imetelstat group compared to 47% in the placebo group. Of these, neutropenia and thrombocytopenia were the most common, and occurred most often during the first three treatment cycles. Cytopenia was managed with treatment delays and dose adjustments in accordance with the study protocol.

Dosage and administration
In the clinical trial, imetelstat 7.5 mg/kg was administered IV over 2 hours every four weeks until disease progression or unacceptable toxicity occurred.

Place in therapy

In MDS, the bone marrow fails to produce healthy blood cells, leading to cytopenia. The incidence rate of MDS is approximately 4.5 per 100,000 people per year in the general population; however, individuals over 60 years of age are most commonly affected. About 90% of cases are primary or idiopathic in nature, resulting from age-related injury to stem cells. The remaining cases are the result of cytotoxic chemotherapy or radiation therapy. The majority of patients (85%) with MDS experience fatigue or shortness of breath due to underlying anemia. Neutropenia and thrombocytopenia usually occur during advanced stages of the disease. Once termed preleukemia, MDS evolves into acute myeloid leukemia (AML) in about 30% of patients.

HSCT is the only available curative treatment for MDS. Allogeneic HSCT is considered in transplant candidates with intermediate or greater risk disease. When HSCT is not appropriate, an alternative therapy is RBC transfusions. Pharmacologic agents include ESAs (e.g., epoetin alfa, darbepoetin) and the erythroid maturation agent luspatercept-aamt (Reblozyl®; for sideroblastic MDS). Agents used to slow progression of the disease include hypomethylating agents (e.g., azacytidine, decitabine) and immune therapy (e.g., lenalidomide). In addition, use of investigational drugs in clinical trials remains an important aspect of MDS management.

Imetelstat is a first-in-class telomerase inhibitor. If approved, imetelstat would provide a new mechanism of action leading to durable transfusion independence when treating MDS-related anemia after treatment with ESAs has failed or in patients who are ESA ineligible. This agent could compete with Reblozyl in patients with ring sideroblastic MDS. On March 14, 2024, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted in favor (12:2) of imetelstat for the treatment of anemia for low-risk MDS patients who are refractory or intolerant to ESAs.

Imetelstat is also in phase 3 trials for myelofibrosis and phase 2 trials for AML.

FDA approval timeline

June 14, 2024

FDA designations: Fast Track, Orphan Drug

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected annual U.S. sales	$54	$213	$350	$467	$566

midomafetamine oral

Manufacturer: Lykos

Proposed indications

Post-traumatic stress disorder (PTSD)

Clinical overview

Mechanism of action
Midomafetamine (MDMA) is a psychoactive entactogen. It promotes the release of monoamines and hormones in the brain, including serotonin, norepinephrine, dopamine, oxytocin and cortisol that modulate emotional memory circuitry.

Clinical trials
Two multi-site, double-blind, phase 3 trials, MAPP1 (NCT03537014; n=90) and MAPP2 (NCT04077437; n=104), evaluated MDMA in patients with severe or moderate to severe PTSD, respectively. Patients were randomized 1:1 to MDMA or placebo, each used in combination with psychotherapy. The primary endpoint in both trials was change from baseline in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score at week 18; a ≥ 10-point reduction in CAPS-5 total severity score was considered clinically meaningful. The mean baseline CAPS-5 total severity score was 39 points in MAPP1 and 44.1 points in MAPP2. Both trials met the primary endpoint, demonstrating a significant improvement in the CAPS-5 total severity score with MDMA compared to placebo (MAPP1: LS mean change, -4.4 versus -13.9, respectively [p<0.001]; MAPP2: LS mean change, -23.7 versus -14.8, respectively; [p<0.001]). In MAPP1, 67% of patients treated with MDMA no longer met the diagnostic criteria for PTSD and 33% achieved PTSD remission, compared to 32% and 5% of patients, respectively, who were given placebo. A similar trend was reported based on exploratory data in MAPP2. In addition, there was a significant improvement in the key secondary endpoint of Sheehan Disability Scale (SDS) functional impairment score from baseline to week 18 with MDMA compared to placebo (MAPP-1: LS mean change, -3.1 versus -2; respectively [p=0.0116]; MAPP-2: LS mean change, -3.3 versus -2.1; respectively [p=0.03]). In MAPP1, one and three patients in the MDMA and placebo groups, respectively, did not complete therapy due to adverse effects or treatment distress. In MAPP2, the dropout rate was 1.9% in the MDMA group and 15.7% in the placebo group. Suicidal ideation was not increased or intensified by MDMA. No cardiac events indicating QT prolongation occurred with MDMA. In addition, no potential for abuse of MDMA was reported.

Patients in the phase 3 trials were allowed to participate in a long-term follow-up study and were assessed ≥ 6 months after their last therapy session with MDMA or placebo. Interim data revealed durable improvements in CAPS-5 total severity score ≥ 6 months after the last dosing session, and for over a year among those who were followed for more than a year.

Dosage and administration
The treatment period in each trial consisted of three 8-hour experimental sessions during which patients received psychotherapy in addition to oral MDMA or placebo. The sessions were conducted approximately four weeks apart. At session 1, MDMA was given as 80 mg, followed by a supplemental 40 mg dose 1.5 to 2 hours later. In sessions 2 and 3, MDMA was given as 120 mg, followed by a supplemental 60 mg dose 1.5 to 2 hours later.

Place in therapy

PTSD is a psychiatric condition that can occur in a person of any age who experiences or witnesses a traumatic event or series of events with a threat of injury or actual injury to themselves or others. It is estimated that PTSD affects about 8 to 12 million people in the U.S. in a given year, with a higher likelihood in women and minority groups. Symptoms of PTSD are severe enough to interfere in daily life. To meet the DSM-5 diagnosis for PTSD, all of the following symptoms must be present for at least one month: re-experiencing the event (e.g., flashback, nightmares), avoidance of trauma-related stimuli, arousal and reactivity symptoms (e.g., irritability, insomnia, easily startled, engaging in risky behavior), and cognition and mood symptoms (e.g., negative thoughts and emotions, feeling isolated). PTSD symptoms typically begin within 3 months of the traumatic event, but can present at any time, even decades after the event. PTSD is also associated with comorbidities, such as depression, anxiety, substance use and abuse, dissociative disorders, and harm toward self and others.

Trauma-focused psychotherapy aids in processing and moderating memories associated with trauma using in vivo and/or imaginal exposure. Trauma-focused psychotherapy is the first-line treatment for PTSD and includes techniques such as cognitive behavioral therapy (CBT), cognitive processing therapy (CPT), cognitive therapy (CT), prolonged exposure therapy (PE), brief eclectic psychotherapy (BEP), eye movement desensitization and reprocessing (EMDR) and narrative exposure therapy (NET). While trauma-focused psychotherapy has proven to be effective, up to 50% of patients treated have lasting symptoms and nearly 25% do not complete therapy. Medication therapy (e.g., SSRIs) is an alternative first-line treatment in patients with comorbidities (e.g., depression, anxiety) or who are unable to participate in psychotherapy. Paroxetine (Paxil®) and sertraline (Zoloft®) are FDA-approved for PTSD; efficacy rates of ≤ 60% and remission rates of < 30% have been reported for these agents. Fluoxetine (Prozac®) and venlafaxine (Effexor® XR) are also recommended off-label. Evidence for combined psychotherapy and pharmacotherapy compared with psychotherapy alone is mixed.

MDMA promotes the release of monoamines and hormones in the brain that modulate emotional memory circuitry. Neuroimaging findings suggest that MDMA acts in key neural pathways responsible for memory and emotional processing (e.g., amygdala, hippocampus, prefrontal cortex). MDMA appears to facilitate reprocessing of traumatic memories with clearer recall and empathy for oneself, and without anxiety, emotional numbing or dissociation. In clinical trials, MDMA + trauma-focused psychotherapy led to a significant and durable improvement in PTSD symptoms compared to placebo, when administered in a setting designed to enhance and support the therapeutic effects of the agent. MDMA was well-tolerated, without increase in risk in suicidality, CV effects or abuse potential of the agent.

If approved, MDMA would be the first FDA-approved psychedelic agent and will be used in combination with psychotherapy for PTSD. Also known as ecstasy, MDMA is currently a Schedule I Controlled Substance in the U.S. and will require rescheduling by the DEA to allow for prescription use. Notably, states could have unique regulations to legalize and/or govern use. Another psychedelic agent, psilocybin, is also in clinical trials for PTSD (phase 2), as well as MDD (phase 3) and eating disorders (phase 2).

FDA approval timeline

August 11, 2024

FDA designations: Breakthrough Therapy, Priority Review

Financial forecast (reported in millions)

The projected total U.S. sales for MDMA are not available.

nemolizumab SC

Manufacturer: Galderma

Proposed indications

Prurigo nodularis
Moderate to severe atopic dermatitis

Clinical overview

Mechanism of action
Nemolizumab is a monoclonal antibody targeting interleukin-31 receptor alpha (IL-31α), which blocks signaling from IL-31.

Clinical trials

The randomized, double-blind, phase 3 OLYMPIA 2 trial (NCT04501679) evaluated nemolizumab in 274 adults with moderate to severe prurigo nodularis. The primary endpoints were itch response, defined as a reduction of ≥ 4 points on the Peak Pruritus Numerical Rating Scale (PP-NRS), with scores ranging from 0 to 10 (higher scores indicating more severe itch) and an IGA response of 0 (clear) or 1 (almost clear) accompanied by a reduction from baseline to week 16 of ≥ 2 points. At week 16, higher proportions of patients in the nemolizumab group compared to those in the placebo group achieved an itch response (56.3% versus 20.9%; p<0.001) and an IGA response (37.7% versus 11%; p<0.001). Significant improvements in itch intensity and sleep disturbance, both secondary endpoints, were seen by week 4 with nemolizumab compared to placebo. The most common TEAEs with nemolizumab were headache and atopic dermatitis. Top-line results from the OLYMPIA 1 trial (NCT04501666) reported similar outcomes based on itch response and IGA response with nemolizumab compared to placebo (itch, 58.4% versus 16.7%, respectively [p<0.0001]; IGA, 26.3% versus 7.3%, respectively [p<0.0001]) at 16 weeks. In addition, interim data from the open-label, phase 3, long-term OLYMPIA-LTE trial (NCT04204616) demonstrated continuous improvement in skin lesions, itch, sleep disturbance, and QOL up to week 52 with nemolizumab. No new safety signals were reported at 52 weeks.

Nemolizumab was also evaluated in the identical ongoing, randomized, double-blind, phase 3 ARCADIA 1 (NCT03985943) and ARCADIA 2 (NCT03989349) trials for the treatment of moderate to severe atopic dermatitis. Combined, the trials enrolled over 1,700 patients ≥ 12 years of age who continued background topical steroid or topical calcineurin inhibitor therapy. After 16 weeks, 43.5% of patients in ARCADIA 1 and 42.1% in ARCADIA 2 who were treated with nemolizumab achieved the primary endpoint of 75% reduction in the Eczema Area and Severity Index (EASI) compared to 29% and 30.2%, respectively, of patients who received placebo (p<0.0001 and p=0.0011). In both studies, significant improvement in sleep disturbance (secondary endpoint) was also seen at 16 weeks with nemolizumab compared to placebo. Galderma has also initiated a long-term trial, ARCADIA-LTE, for nemolizumab for moderate to severe atopic dermatitis.

Dosage and administration
In the clinical trials, nemolizumab was self-administered SC at an initial 60 mg dose, followed by 30 mg or 60 mg, depending on baseline body weight, every 4 weeks.

Place in therapy

Prurigo nodularis (PN) is a rare, chronic inflammatory skin condition characterized by raised, hyperkeratotic lesions on the arms, legs, and trunk. PN is often severely itchy and can have a marked negative effect on sleep and QOL. PN affects about 72 out of every 100,000 people in the U.S. People at increased risk for developing PN include patients ≥ 50 years of age, people who are Black, and those who have chronic conditions, such as atopic dermatitis, diabetes, ESRD, hepatitis C, untreated HIV, lymphoma, thyroid conditions, anxiety, or depression. PN treatments include topical emollients, menthol, pramoxine, capsaicin, corticosteroids, calcineurin inhibitors, and calcipotriol. Intradermal corticosteroids, cryosurgery, and phototherapy are useful in patient who fail topical agents. Systemic agents include antihistamines, as well as off-label use of antidepressants, gabapentin, methotrexate and thalidomide. In September 2022, the IL-4 receptor alpha antagonist dupilumab (Dupixent) became the first agent FDA-approved for PN in adults. In clinical trials, Dupixent led to reduction in itch (based on Worst Itch Numeric Rating Scale [WI-NRS] by ≥ 4 points from baseline) in 60% of patients and IGA of 0 or 1 in 48% of patients, compared to 18.4% of patients for each measure in the placebo group.

Atopic dermatitis (AD) is a common, chronic inflammatory skin condition characterized by persistent itch and recurrent skin lesions. It affects an estimated 31.6 million (10.1%) people in the U.S., including 9.6 million children and adolescents. Approximately 30% and 40% of cases in pediatrics and adults, respectively, are moderate to severe. Onset typically occurs before 6 years of age. While several systemic DMTs are available to treat moderate and severe AD, topical emollients, corticosteroids, and immunomodulators remain important options; however, long-term continuous use of topical steroids and immunomodulators is limited by TEAEs. The Janus kinase inhibitors abrocitinib (Cibinqo®; oral), upadacitinb (Rinvoq®; oral), and ruxolitinib (Opzelura®; topical), topical PDE5 inhibitor crisaborole (Eucrisa®), injectable IL‑13 inhibitor tralokinumab (Adbry®) and IL-4/IL-13 inhibitor dupilumab (Dupixent) are also indicated to treat AD.

Nemolizumab is a first-in-class monoclonal antibody that inhibits IL-31 and is designed to reduce burdensome itch related to chronic inflammatory skin conditions. If approved, it will be the second biologic agent approved for PN and will compete directly with Dupixent, a drug with efficacy and safety data across several immunologic conditions. Although there are no head-to-head trials, nemolizumab appears to demonstrate similar safety and efficacy to Dupixent in patients with PN, but may also gain approval in adolescents, an age group that Dupixent does not cover for PN. In addition, nemolizumab has been submitted to the FDA to treat atopic dermatitis in adults and adolescent patients. If approved, it may compete with Dupixent and Adbry in this space.

FDA approval timeline

Prurigo nodularis: August 14, 2024

FDA designations: Breakthrough Therapy, Priority Review

Atopic dermatitis: December 14, 2024

Financial forecast (reported in millions)

The projected total U.S. sales for nemolizumab are not available.

tarlatamab IV

Manufacturer: Amgen

Proposed indications

Advanced small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Clinical overview

Mechanism of action
Tarlatamab is a bispecific T-cell engager (BiTE) that targets delta-like ligand 3 (DLL3) in neuroendocrine cancers, including SCLC.

Clinical trials
The open-label, phase 2 DeLLphi-301 trial (NCT05060016) evaluated tarlatamab in 220 patients with SCLC who had relapsed after, or was refractory to, one platinum-based treatment regimen and at least one other line of therapy. Eligible patients included those with asymptomatic, treated, stable brain metastases. Patients were randomized 1:1 to receive tarlatamab 10 mg or 100 mg doses. In the 10 mg group, at a median follow-up of 10.6 months, the ORR (primary endpoint) was 40%, with a complete response rate of 1%. In the 10 mg group, 59% and 25% of patients had a DOR ≥ 6 months and ≥ 9 months, respectively, and the PFS was 4.9 months. In the 100 mg group, at a median follow-up of 10.3 months, the ORR was 32%, with a complete response rate of 8%. Among patients who received 100 mg, 61% and 36% experienced a DOR ≥ 6 months and ≥ 9 months, respectively, and the PFS was 3.9 months. Most patients with an evaluable tumor-tissue sample (96% in each group) had DLL3 tumor expression; however, no difference in tumor reduction was seen based on DLL3 expression. The most common TEAEs reported were CRS and pyrexia. Grade 3 TEAEs occurred less often with the 10 mg dose (1%) versus the 100 mg dose (6%).

Dosage and administration
In the clinical trial, tarlatamab was administered IV over 60 minutes at a dose of 10 mg or 100 mg every 2 weeks.

Place in therapy

Approximately 20% of all lung cancers are neuroendocrine tumors, of which nearly 14% are SCLC. Most cases of SCLC are associated with cigarette smoking. SCLC is an aggressive disease in which widespread metastases develop early in the disease course. The incidence of new cases of SCLC in the U.S. in 2023 was estimated at 33,000.

Systemic therapy is the SOC for patients with SCLC. A platinum agent + etoposide is recommended for all stages of the disease, with the addition of a PD-L1 blocker to treat extensive-stage disease, including cases in which brain metastases are present. Subsequent systemic therapies include platinum-based doublet, lurbinectedin, topotecan and irinotecan. In addition, concurrent radiation therapy may provide benefit at all stages of the disease as part of treatment and palliation; however, surgical resection is recommended only in a small proportion (5%) of patients with stage I-IIA (T1-2, N0, M0) SCLC.

Response rates to initial therapy are high, at about 70% to 90% for limited disease and approximately 60% for extensive disease. Unfortunately, most patients will relapse, and response to subsequent systemic therapy is poor and dependent on the time elapsed from initial therapy (response rate, ≤ 10% with interval ≤ 6 months and 25% with interval > 6 months).

DLL3 is highly expressed on the cell surface of neuroendocrine tumors and is present in the majority (≥ 85%) of patients with SCLC, making it a potential target in treating SCLC. Tarlatamab is a first-in-class agent that binds to both DLL3 on cancer cells and CD3 on T cells, leading to T cell-mediated lysis of the tumor cells. If approved, it will provide a new approach to combat SCLC, a disease with a large unmet need. It remains to be seen if tarlatamab will be used as second- or third-line systemic treatment. Most patients in the DeLLphi-301 clinical trial had ≥ 2 prior lines of therapy; however, the NCCN guidelines for SCLC do not distinguish between second- and third-line therapies, and instead offer recommendations based on primary and subsequent treatment options.

Amgen is also evaluating tarlatamab in phase 3 trials for SCLC, which include DeLLphi-304 comparing tarlatamab monotherapy with SOC chemotherapy (lurbinectedin, topotecan, amrubidin) for second-line treatment and DeLLphi-306 evaluating tarlatamab after chemoradiotherapy in earlier settings of SCLC.

FDA approval timeline

June 12, 2024
FDA designations: Breakthrough Therapy, Orphan Drug, Priority Review, RTOR

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected annual U.S. sales	$21	$69	$128	$205	$274

xanomeline-trospium (KarXT) oral

Manufacturer: Karuna

Proposed indications

Schizophrenia

Clinical overview

Mechanism of action
KarXT is a combination of xanomeline and trospium. Xanomeline is an antipsychotic agent with dual M1/M4 muscarinic acetylcholine receptor agonist activity and trospium is a muscarinic receptor antagonist that counteracts the peripheral muscarinic adverse effects of xanomeline.

Clinical trials

The randomized, double-blind, phase 3 EMERGENT-2 trial (NCT04659161) evaluated KarXT in 252 patients 18 to 65 years of age with schizophrenia who were hospitalized due to a recent worsening of psychosis (PANSS score ≥ 80, CGI-S ≥ 4). After a washout period of their background schizophrenia medications, patients were randomized 1:1 to KarXT or placebo. At week 5, patients treated with KarXT showed a statistically significant and clinically meaningful reduction in the PANSS total score (primary endpoint) compared to patients who were given placebo (mean change from baseline, -21.2 versus -11.6 points, respectively; difference, -9.6 points; p<0.0001). At week 5, KarXT also led to significant improvements from baseline in secondary endpoints compared to placebo including the PANSS positive subscale (-6.8 versus -3.9 points, respectively), PANSS negative subscale (-3.4 versus -1.6 points, respectively), PANSS Marder Factor negative score (-4.2 versus -2 points, respectively) and CGI-S (-1.2 versus -0.7 points, respectively) as well as the proportion of patients who experienced ≥ 30% reduction in PANSS total score (54.8% versus 28.3%, respectively) (p<0.05 for each endpoint). The most common TEAEs with KarXT (≥ 10%) were mild to moderate constipation, dyspepsia, headache, nausea, vomiting and hypertension. Discontinuation rates were similar between the two groups. KarXT was not associated with extrapyramidal or metabolic effects.

In the similarly designed randomized, double-blind, phase 3 EMERGENT-3 trial ((NCT04738123; n=256), KarXT also met its primary endpoint of reduction in PANSS total score at week 5 with an 8.4-point reduction in PANSS total score compared to placebo (p<0.0001). In addition, it demonstrated a clinically meaningful and statistically significant 3.5-point reduction in PANSS positive subscale compared to placebo (-7.1 versus -3.6 points, respectively; p<0.0001). While it showed reductions in the PANSS negative subscale, the change from baseline was not statistically significant at week 5; improvement in this subscale only achieved statistical significance at week 4 (p<0.05). The adverse event profile was generally similar to that reported in EMERGENT-2.

The PANSS total score ranges from 30 to 210 points. PANSS positive, negative and Marder Factor negative subscale scores each range from 7 to 49 points. A decrease in the PANSS score correlates with an improvement in schizophrenia symptoms. The CGI-S score ranges from 1 to 7, with 7 indicating the most severe illness.

Dosage and administration
In the clinical trials, KarXT was administered orally twice daily at xanomeline/trospium doses of 50 mg/20 mg on days 1 and 2, then 100 mg/20 mg on days 3 through 7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg/30 mg and the option to return to 100 mg/20 mg based on tolerability.

Place in therapy

Schizophrenia is a serious mental illness that affects 1% of the population. Schizophrenia manifests as positive symptoms (hallucination, delusion, and thought and movement disorder), negative symptoms (lack of emotion, pleasure, motivation and social interaction), and cognitive deficits (impaired executive function, attention and working memory). The onset of schizophrenia usually occurs between the late teens and the mid-30s. Schizophrenia can be debilitating, leading to non-fatal suicide attempts in approximately 20% to 40% of patients, and fatal attempts in approximately 4% to 5% of patients.

Psychosocial therapy, including cognitive-behavioral therapy, cognitive remediation, and social cognition training, is essential treatment for schizophrenia. Antipsychotics are the standard drugs used in patients with schizophrenia. They include first-generation antipsychotics (FGAs) (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, thiothixene, trifluoperazine) and second-generation antipsychotics (SGAs), also known as atypical antipsychotics (e.g., aripiprazole, asenapine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, risperidone, quetiapine, ziprasidone). Available antipsychotic agents have proven efficacy in treating positive symptoms of schizophrenia, but their efficacy for negative or cognitive symptoms is limited. FGAs work primarily by blocking dopamine (D2) receptors in the brain and are associated with extrapyramidal adverse effects, tardive dyskinesia, and hyperprolactinemia. SGAs block dopamine D2 receptors and serotonin 2A (5-HT2A) receptors and are generally more likely to cause weight gain and abnormal glucose and lipid levels. The approach to treatment of schizophrenia is largely based on trial and error due to patient variation in response and medication side effects. There is no preference between FGAs or SGAs, or between drugs within each group. However, clozapine is recommended in patients with treatment-resistant schizophrenia and in patients with a significant risk of suicide or aggressive behavior but is not recommended as first-line treatment due to serious side effects (e.g., agranulocytosis).

There are significant unmet needs in the treatment of schizophrenia, especially for the treatment of cognitive impairment and negative symptoms. In addition, side effect profiles contribute to a non-adherence rate estimated at 40% to 50%. Also, approximately 20% of patients will relapse after 1 year of being on an antipsychotic agent.

If approved, KarXT will herald in the first new mechanism of action to treat schizophrenia in several decades. Unlike FGAs and SGAs, it provides selective M1/M4 muscarinic receptor agonism through xanomeline without directly impacting dopamine D2 receptors and mitigates muscarinic TEAEs through the use of trospium. Phase 3 trials demonstrate that KarXT is effective for treating positive symptoms of schizophrenia in the short-term; however, the effects on negative symptoms and cognitive processes are inconclusive. Long-term efficacy and safety, particularly regarding tardive dyskinesia and metabolic effects, are uncertain. Due to the lack of long-term data, ICER rated the net health benefit of KarXT as promising, but inconclusive.

KarXT is also in a phase 3 trial as adjunctive therapy in schizophrenia (ARISE trial; non-hospitalized patients) and for the treatment of neuropsychiatric symptoms in Alzheimer’s disease (ADEPT program).

FDA approval timeline

September 26, 2024

Financial forecast (reported in millions)

The financial forecast for tradipitant is not currently available.

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$43	$307	$700	$1,085	$1,371

Keep on your radar

Notable agents that are further from approval have been identified in this unique watch list. These are products with the potential for significant clinical and financial impact. Their development status is being tracked on the Quarterly Pipeline radar. These pipeline products, their respective class or proposed indication, as well as an estimated financial forecast for the year 2028, are displayed. The financials are projected total annual U.S. sales, reported in millions.

Drug Generic Name	Therapeutic category	April 2024 Pipeline - Total US sales for 2028 (Dollars in millions)
acoramidis	Cardiology	$508
arimoclomol	Metabolic	$78
axatilimab	Oncology	$122
crovalimab	Immunology	$189
datopotamab deruxtecan	Oncology	$984
donanemab	Neurology	$1,645
eladocagene exuparvovec	Neurology/Gene Tx	$81
garadacimab	Hematology	$175
govorestat	Metabolic	$47
marstacimab	Hematology	$221
obecabtagene autoleucel	Oncology/Cellular therapy	$145
palopegteriparatide	Endocrine	$752
patritumab deruxtecan	Oncology	$688
revumenib	Oncology	$298

Drug list

The pipeline drug list is an aerial outline of drugs with anticipated FDA approval through 2026. It is not intended to be a comprehensive inventory of all drugs in the pipeline; emphasis is placed on drugs in high-impact categories. Investigational drugs with a recent Complete Response Letter (CRL) are also reported.

Gene & cellular therapies

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
fidanacogene elaparvovec	Pfizer/Genentech	Hemophilia B (adults)	IV	BLA; Breakthrough Therapy; Orphan Drug; RMAT	Apr-Jun 2024
prademagene zamikeracel	Abeona	Epidermolysis bullosa (recessive dystrophic)	Topical	BLA; Breakthrough Therapy; Orphan Drug; Priority Review; RMAT; RPD	05/25/2024
marnetegragene autotemcel	Rocket	Leukocyte adhesion deficiency-I	IV	BLA; Fast Track; Orphan Drug; Priority Review; RPD; RMAT	06/29/2024
afamitresgene autoleucel	Adaptimmune	Synovial sarcoma (advanced)	IV	BLA; Orphan Drug; Priority Review; RMAT	08/04/2024
obecabtagene autoleucel	Autolus	ALL (R/R, B cell)	IV	BLA; Orphan Drug; RMAT	11/27/2024
eladocagene exuparvovec	PTC	Aromatic L-amino acid decarboxylase (AADC) deficiency	Intracerebral	BLA; Orphan Drug; RPD	03/19/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
lisocabtagene maraleucel (Breyanzi®)	Bristol-Myers Squibb	Follicular lymphoma (R/R)	IV	sBLA; Orphan Drug; Priority Review	05/23/2024
lisocabtagene maraleucel (Breyanzi)	Bristol-Myers Squibb	Mantle cell lymphoma (R/R, prior BTK inhibitor therapy)	IV	sBLA; Orphan Drug; Priority Review	05/31/2024
delandistrogene moxeparvovec (Elevidys)	Sarepta	DMD (confirmed mutation in the DMD gene; no age limit)	IV	sBLA; Fast Track; Orphan Drug; Priority Review; RPD	06/21/2024

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
AAV8-ranibizumab (RGX-314)	Abbvie	DME; Wet AMD	Subretinal	BLA; Orphan Drug	TBD
aglatimagene besadenovec	Candel	Prostate cancer	Intratumorally	BLA; Fast Track	TBD
allogeneic adult stem cells (CAP-1002)	Nippon Shinyaku	DMD	IV	BLA; Orphan Drug; RMAT; RPD	TBD
autologous kidney cells (ReACT)	ProKidney	CKD	Hepatic injection	BLA; RMAT	TBD
botaretigene sparoparvovec	Janssen	Retinitis pigmentosa	Subretinal	BLA; Fast Track; Orphan Drug	TBD
dirloctocogene samoparvovec	Genentech	Hemophilia A	IV	BLA; Breakthrough, Orphan	TBD
giroctocogene fitelparvovec	Pfizer	Hemophilia A	IV	BLA; Fast Track; Orphan Drug; RMAT	TBD
RGX-121	Regenxbio	Mucopolysaccharidosis II (MPS II; Hunter Syndrome)	CNS injection	BLA; Fast Track; Orphan Drug; RMAT; RPD	TBD
tabelecleucel	Pierre Fabre	Epstein-Barr virus-associated post-transplant lymphoproliferative disease	IV	BLA; Breakthrough Therapy; Orphan Drug	TBD

None

Biosimilars

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
insulin aspart (biosimilar to Novo Nordisk's Novolog®)	Gan & Lee/Sandoz	T1DM; T2DM	SC	BLA	4/14/2024
ranibizumab (biosimilar to Genentech's Lucentis®)	STADA Arzneimittel/Xbrane	Diabetic retinopathy; DME; Myopic choroidal neovascularization; Macular edema following RVO; Wet AMD	Intravitreal	BLA	4/21/2024
aflibercept (biosimilar to Regeneron's Eylea®)	Amgen	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	BLA	May-Jul 2024
rituximab (biosimilar to Genentech’s Rituxan®)	Dr. Reddy's	CCL; Granulomatosis with polyangiitis/microscopic polyangiitis; NHL; Mature B-cell NHL/mature B-cell acute leukemia; Pemphigus vulgaris; RA	IV	BLA	05/10/2024
aflibercept (biosimilar to Regeneron's Eylea)	Celltrion	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	BLA	06/28/2024
aflibercept (biosimilar to Regeneron's Eylea)	Coherus	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	BLA	06/28/2024
ustekinumab (biosimilar to Janssen’s Stelara®)	Formycon	PSO; PsA; CD; UC	IV, SC	BLA	September 2024
ustekinumab (biosimilar to Janssen's Stelara)	Intas	PSO; PsA; CD; UC	SC	BLA	11/04/2024
ustekinumab (biosimilar to Janssen's Stelara)	Biocon/Janssen	PSO; PsA; CD; UC	SC	BLA	12/27/2024
insulin aspart (biosimilar to Novo Nordisk's Novolog)	Amphastar	T1DM; T2DM	SC	BLA	01/10/2025
tocilizumab (biosimilar to Genentech's Actemra®)	Celltrion	RA; Giant cell arteritis; systemic sclerosis-associated interstitial lung disease; JIA (polyarticular, systemic); CRS; COVID-19	IV, SC	BLA	01/28/2025
aflibercept (biosimilar to Regeneron's Eylea)	Biocon/Janssen	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	BLA	Pending
eculizumab (biosimilar to Alexion’s Soliris®)	Amgen	PNH; Hemolytic uremic syndrome (atypical)	IV	BLA	Pending
insulin glargine (biosimilar to Sanofi's Lantus®)	Gan & Lee/Sandoz	T1DM; T2DM	SC	BLA	Pending
insulin lispro (biosimilar to Eli Lilly's Humalog®)	Gan & Lee/Sandoz	T1DM; T2DM	SC	BLA	Pending
pegfilgrastim (biosimilar to Amgen's Neulasta®)	Lupin	Neutropenia/leukopenia	SC	BLA	Pending
trastuzumab (biosimilar to Genentech’s Herceptin®)	Henlius/Accord	Breast cancer; Gastric or gastroesophageal junction adenocarcinoma	IV	BLA	Pending

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
adalimumab-bwwd 40 mg/0.4 mL (Hadlima™) (biosimilar to Abbvie’s Humira®)	Organon	RA; AS; PSO; PsA; JIA; CD; UC; HS; Uveitis	SC	sBLA for interchangeability	09/06/2024

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
aflibercept (biosimilar to Regeneron’s Eylea®)	Sandoz	DME; Wet AMD	Intravitreal	BLA	TBD
bevacizumab (biosimilar to Genentech’s Avastin®)	Essex	DME; Wet AMD	IV	BLA	TBD
insulin aspart (biosimilar to Novo Nordisk's Novolog®)	Amphastar	T1DM	SC	BLA	TBD

None

Specialty

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
donanemab	Eli Lilly	Alzheimer's disease (early, symptomatic)	IV	BLA; Breakthrough Therapy	Apr-Jun 2024
nogapendekin alfa inbakicept	Immunitybio	Bladder cancer (BCG-unresponsive, non-muscle-invasive, carcinoma in situ [CIS], with or without Ta or T1 disease)	Intravesical	BLA; Breakthrough Therapy; Fast Track	4/23/2024
mavorixafor	X4	Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (ages ≥ 12 years)	Oral	NDA; Breakthrough Therapy; Fast Track; Orphan Drug; Priority Review; RPD	04/30/2024
tovorafenib	Day One	Glioma (relapsed/progressive, low-grade, monotherapy)	Oral	NDA; Breakthrough Therapy; Orphan Drug; Priority Review; RPD	04/30/2024
palopegteriparatide	Ascendis	Hypoparathyroidism	SC	NDA; Orphan Drug	05/14/2024
camrelizumab	Jiangsu Hengrui	HCC (unresectable, 1st-line, in combination with rivoceranib)	IV	BLA; Orphan Drug	05/16/2024
rivoceranib	Elevar	HCC (unresectable, 1st-line, in combination with camrelizumab)	Oral	NDA; Orphan Drug	05/16/2024
elafibranor	Genfit/Ipsen	Primary biliary cholangitis	Oral	NDA; Breakthrough Therapy; Orphan Drug; Priority Review	06/10/2024
tarlatamab	Amgen	SCLC (advanced)	IV	BLA; Breakthrough Therapy; Orphan Drug; Priority Review; RTOR	06/12/2024
imetelstat	Geron	Myelodysplastic syndrome (lower-risk, transfusion-dependent anemia, failed ESAs)	IV	NDA; Fast Track; Orphan Drug	06/14/2024
patritumab deruxtecan	Merck	NSCLC ( locally advanced or metastatic, EGFR-mutated, ≥ 2 prior systemic therapies)	IV	BLA; Breakthrough Therapy; Priority Review	06/26/2024
polyspecific immunoglobulin preparation	Biotest	Primary immunodeficiencies	IV	BLA	06/29/2024
SH-105	Shorla	Breast cancer; Ovarian cancer	IV	NDA	06/29/2024
deuruxolitinib	Sun	Alopecia areata (moderate-severe)	Oral	NDA; Breakthrough Therapy; Fast Track	July 2024
crovalimab	Genentech	PNH	IV, SC	BLA; Breakthrough Therapy; Orphan Drug	07/27/2024
dasatinib	Xspray	CML	Oral	505(b)(2) NDA; Orphan Drug	07/31/2024
midomafetamine	Lykos	PTSD (in combination with trauma-focused psychotherapy)	Oral	NDA; Breakthrough Therapy; Priority Review	08/11/2024
denileukin diftitox	Citius	Cutaneous T cell lymphoma (R/R, ≥ 2nd-line)	IV	BLA; Orphan Drug	08/13/2024
nemolizumab	Galderma	Prurigo nodularis	SC	BLA; Breakthrough Therapy; Priority Review	08/14/2024
seladelpar	Cymabay	Primary biliary cholangitis (including pruritus, ursodeoxycholic acid inadequate response/intolerance)	Oral	NDA; Breakthrough Therapy; Orphan Drug; Priority Review	08/14/2024
vorasidenib	Servier	Glioma (diffuse, IDH-mutant )	Oral	NDA; Breakthrough Therapy; Fast Track; Orphan Drug; Priority Review	08/20/2024
linvoseltamab	Regeneron	Multiple myeloma (R/R, 4th-line)	IV	BLA; Fast Track; Orphan Drug; Priority Review	08/22/2024
axatilimab	Syndax	Chronic GVHD (failure of ≥ 2 prior lines of systemic therapy, ages ≥ 6 years)	IV	BLA; Fast Track; Orphan Drug; Priority Review	08/28/2024
atezolizumab SC (Tecentriq®)	Genentech	Alveolar soft part sarcoma; HCC; Melanoma; NSCLC; SCLC; Urothelial cancer	SC	BLA	September 2024
ocrelizumab SC (Ocrevus®)	Genentech	MS	SC	BLA	September 2024
ACAM2000	Emergent	Monkeypox (Mpox)	Scarification	BLA	09/06/2024
arimoclomol	Zevra	Niemann-Pick disease type C	Oral	NDA; Breakthrough Therapy; Fast Track; Orphan Drug; RPD	09/21/2024
N-acetyl-L-leucine	Intrabio	Niemann-Pick disease type C	Oral	NDA; Fast Track; Orphan Drug; Priority Review; RPD	09/24/2024
revumenib	Syndax/Abbvie	AML (R/R, KMT2A-rearranged)	Oral	NDA; Breakthrough Therapy; Orphan Drug; Priority Review; RTOR	09/26/2024
garadacimab	CSL	HAE	SC	BLA; Fast Track; Orphan Drug	Oct-Nov 2024
marstacimab	Pfizer	Hemophilia A and B (without factor VIII or IX inhibitors)	IV, SC	BLA; Fast Track; Orphan Drug	Oct-Dec 2024
paliperidone palmitate ER	Luye	Schizophrenia	IM	505(b)(2) NDA	10/09/2024
octreotide	Novartis	Acromegaly	SC	NDA	10/21/2024
govorestat	Applied Therapeutics	Galactosemia	Oral	NDA; Fast Track; Orphan Drug; Priority Review; RPD	11/28/2024
acoramidis	Bridgebio	Transthyretin amyloid cardiomyopathy (ATTR-CM)	Oral	NDA	11/29/2024
zanidatamab	Jazz	Biliary tract cancer (unresectable, locally advanced or metastatic, HER2+, previously-treated)	IV	BLA; seeking Accelerated Approval; Breakthrough Therapy; Fast Track; Orphan Drug	Dec 2024-Apr 2025
nemolizumab	Galderma	Atopic dermatitis (moderate-severe)	SC	BLA	12/14/2024
irinotecan liposome	CSPC	Pancreatic cancer	IV	505(b)(2) NDA	12/18/2024
datopotamab deruxtecan	Daiichi Sankyo/AstraZeneca	NSCLC (locally advanced or metastatic, nonsquamous, ≥ 2-line)	IV	BLA	12/20/2024
glepaglutide	Zealand	Short bowel syndrome (dependent on parenteral support)	SC	NDA; Orphan Drug	12/22/2024
ensartinib	Xcovery	NSCLC (metastatic, ALK+)	Oral	NDA	12/28/2024
elamipretide	Stealth	Barth syndrome	SC	NDA; Fast Track; Orphan Drug; RPD	Jan-Feb 2025
datopotamab deruxtecan	Daiichi Sankyo/AstraZeneca	Breast cancer (HR+/HER2-, IHC 0, IHC 1+ or IHC 2+/ISH-, unresectable or metastatic)	IV	BLA	01/29/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
durvalumab (Imfinzi®)	AstraZeneca	NSCLC (neoadjuvant)	IV	sBLA; Breakthrough Therapy; Fast Track	Apr-Jun 2024
valbenazine (Ingrezza®) oral granules	Neurocrine Biosciences	Huntington's disease chorea; Tardive dyskinesia	Oral	sNDA; Orphan Drug	04/30/2024
rilpivirine (Edurant®)	Janssen	HIV-1 infection (in children weighting ≥ 10 kg)	Oral	sNDA	05/28/2024
alectinib (Alecensa®)	Genentech	NSCLC (ALK+, postoperative adjuvant)	Oral	sNDA; Priority Review	05/30/2024
vedolizumab (Entyvio®)	Takeda	CD (SC maintenance following IV induction)	SC	sBLA	Jun-Jul 2024
sarilumab (Kevzara®)	Sanofi	JIA (polyarticular-course)	SC	sBLA	06/10/2024
repotrectinib (Augtyro™)	Bristol-Myers Squibb	Solid tumors (locally advanced or metastatic, NTRK gene fusion)	Oral	sNDA; Breakthrough Therapy; Fast Track; Priority Review	06/15/2024
adagrasib (Krazati®)	Bristol-Myers Squibb	CRC (KRAS^G12C mutated, locally advanced or metastatic, in combination with cetuximab)	Oral	sNDA; Breakthrough Therapy; Priority Review	06/21/2024
blinatumomab (Blincyto®)	Amgen	ALL (early-stage, CD19-positive B-cell precursor)	IV	sBLA; Breakthrough Therapy; Orphan Drug; Priority Review	06/21/2024
efgartigimod alfa/hyaluronidase-qvfc (Vyvgart® Hytrulo)	Argenx	Chronic inflammatory demyelinating polyneuropathy (CIDP)	SC	sBLA; Orphan Drug; Priority Review	06/21/2024
pembrolizumab (Keytruda®)	Merck	Endometrial carcinoma (primary advanced or recurrent, after chemotherapy)	IV	sBLA; Breakthrough Therapy; Priority Review	06/21/2024
pitolisant (Wakix®)	Harmony	Narcolepsy (excessive daytime sleepiness or cataplexy, ages 6 to 18 years)	Oral	sNDA; Breakthrough Therapy; Fast Track; Orphan Drug; Priority Review	06/21/2024
dupilumab (Dupixent®)	Sanofi/Regeneron	COPD (uncontrolled, add-on therapy)	SC	sBLA; Breakthrough Therapy; Priority Review	06/27/2024
epcoritamab-bysp (Epkinly™)	Genmab/Abbvie	Follicular lymphoma (R/R, ≥ 2 prior lines of systemic therapy)	SC	sBLA; Breakthrough Therapy; Orphan Drug; Priority Review	06/28/2024
risankizumab-rzaa (Skyrizi®)	Abbvie	UC	IV, SC	sBLA	06/28/2024
tislelizumab-jsgr (Tevimbra®)	Beigene	Esophageal squamous cell carcinoma (unresectable, recurrent, locally advanced, or metastatic, 1st-line)	IV	sBLA; Orphan Drug	July 2024
benralizumab (Fasenra®)	AstraZeneca	Eosinophilic granulomatosis with polyangiitis	SC	sBLA; Orphan Drug	Jul-Dec 2024
durvalumab (Imfinzi)	AstraZeneca	Endometrial cancer (1st-line, in combination with olaparib)	IV	sBLA	Jul-Dec 2024
fam-trastuzumab deruxtecan-nxki (Enhertu®)	Daiichi Sankyo	Breast cancer (HER2+, 3rd-line)	IV	sBLA; Breakthrough Therapy; Fast Track	Jul-Dec 2024
olaparib (Lynparza®)	AstraZeneca	Endometrial cancer (1st-line, in combination with durvalumab)	Oral	sNDA	Jul-Dec 2024
amivantamab-vmjw (Rybrevant®)	Janssen	NSCLC (locally advanced or metastatic, EGFR exon 19 deletion or L858R substitution, disease progression on/after osimertinib); NSCLC (locally advanced or metastatic, EGFR exon 19 deletions or L858R substitution, 2nd-line, after disease progression on/after osimertinib, in combination with carboplatin-pemetrexed)	IV	sBLA; Breakthrough Therapy	09/20/2024
bimekizumab (Bimzelx®)	UCB	AS; PsA	SC	sBLA	October 2024
iptacopan (Fabhalta®)	Novartis	IgA Nephropathy (Berger's disease)	Oral	sNDA; seeking Accelerated Approval; Priority Review	October 2024
nivolumab (Opdivo®)	Bristol-Myers Squibb	NSCLC (resectable stage IIA to IIIB, neoadjuvant with chemotherapy, and adjuvant)	IV	sBLA; Breakthrough Therapy	10/08/2024
amivantamab-vmjw (Rybrevant)	Janssen	NSCLC (locally advanced or metastatic, EGFR exon 19 deletion or L858R substitutionm in combination with lazertinib, 1st-line)	IV	sBLA	10/21/2024
avacincaptad pegol (Izervay™)	Astellas	Dry AMD-related geographic atrophy	Intravitreal	sNDA; Breakthrough Therapy; Fast Track	11/19/2024
daratumumab/hyaluronidase-fihj (Darzalex Faspro®)	Janssen	Multiple myeloma (newly diagnosed, in combination with bortezomib, lenalidomide and dexamethasone for induction and consolidation, and with lenalidomide for maintenance)	SC	sBLA	11/28/2024
bimekizumab (Bimzelx®)	UCB	HS (moderate to severe)	SC	sBLA	December 2024
ribociclib (Kisqali®)	Novartis	Breast cancer (adjuvant)	Oral	sNDA; Breakthrough Therapy	December 2024
tislelizumab-jsgr (Tevimbra®)	Beigene	Gastric or gastroesophageal junction adenocarcinoma (locally advanced unresectable or metastatic, in combination with fluoropyrimidine- and platinum-containing chemotherapy)	IV	sBLA	December 2024
lecanemab-irmb (Leqembi®)	Eisai	Alzheimer's disease (mild; once monthly dosing)	IV	sBLA; Breakthrough Therapy; Fast Track	January 2025
guselkumab (Tremfya®)	Janssen	UC (moderate to severe)	SC	sBLA	01/10/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
aficamten	Cytokinetics	Hypertrophic cardiomyopathy	Oral	NDA; Breakthrough Therapy; Orphan Drug	TBD
anti-betv1 antibody (REGN-5713-5714-5715)	Regeneron	Birch allergy	SC	BLA	TBD
anti-BK polyomavirus	Memo	BK polyomavirus infection (renal transplant recipients)	IV	BLA; Fast Track	TBD
apraglutide	Ironwood	Short bowel syndrome	IV, SC	NDA; Orphan Drug	TBD
astegolimab	Genentech	COPD	IV	BLA	TBD
ataluren	PTC	DMD	Oral	NDA; Fast Track; Orphan Drug	TBD
atrasentan	Novartis	IgA nephropathy (Berger's disease)	Oral	NDA	TBD
avutometinib	Verastem	Ovarian cancer	Oral	NDA; Breakthrough Therapy; Orphan Drug	TBD
cannabidiol gel	Harmony	Fragile X syndrome	Topical	NDA; Fast Track; Orphan Drug	TBD
cetuximab sarotalocan	Rakuten	SCCHN	IV	BLA; Fast Track	TBD
clesrovimab	Merck	RSV prevention	IM	BLA	TBD
cobolimab	GlaxoSmithKline	NSCLC	IV	BLA	TBD
crinecerfont	Neurocrine	Congenital adrenal hyperplasia	Oral	NDA; Breakthrough Therapy; Orphan Drug	TBD
crovalimab	Genentech	Hemolytic uremic syndrome	IV, SC	BLA	TBD
CTX-009	Compass	Biliary tract cancer	IV	BLA	TBD
defactinib	Verastem	Ovarian cancer	Oral	NDA; Orphan Drug	TBD
deoxythymidine/deoxycytidine	UCB	Thymidine kinase 2 (TK2) deficiency	Oral	BLA; Breakthrough Therapy; Orphan Drug	TBD
depemokimab	GlaxoSmithKline	Asthma; Chronic rhinosinusitis	SC	BLA	TBD
dersimelagon	Mitsubishi Tanabe	Porphyria	Oral	NDA; Fast Track; Orphan Drug	TBD
dinutuximab beta	EUSA	Neuroendocrine tumors	IV	BLA; Orphan Drug	TBD
donidalorsen	Ionis	HAE	SC	NDA; Orphan Drug	TBD
efruxifermin	Akero	NASH	SC	BLA; Breakthrough Therapy; Fast Track	TBD
etavopivat	Novo Nordisk	SCD	Oral	NDA; Fast Track; Orphan Drug; RPD	TBD
fenebrutinib	Genentech	MS	Oral	NDA	TBD
fianlimab	Regeneron	Melanoma; NSCLC	IV	BLA; Fast Track	TBD
fitusiran	Sanofi	Hemophilia A and B	SC	NDA; Fast Track; Orphan Drug	TBD
garetosmab	Regeneron	Fibrodysplasia ossificans progressiva	IV	BLA; Fast Track; Orphan Drug	TBD
giredestrant	Genentech	Breast cancer (HR+/HER2-)	Oral	NDA; Fast Track	TBD
GBT601	Pfizer	SCD	Oral	NDA; Orphan Drug	TBD
gold nanocrystal	Clene	ALS	Oral	NDA; Orphan Drug	TBD
ianalumab	Novartis	Autoimmune hemolytic anemia; Sjogren's syndrome	SC	BLA	TBD
imlifidase	Sarepta	Kidney transplant rejection	IV	BLA; Fast Track; Orphan Drug	TBD
imsidolimab	Anaptysbio	Generalized pustular psoriasis	IV, SC	BLA; Orphan Drug	TBD
inavolisib	Genentech	Breast cancer (HR+/HER2-, 1st-line)	Oral	NDA	TBD
IONIS-FB-LRx	Ionis/Roche	IgA nephropathy (Berger's disease)	SC	NDA	TBD
itepekimab	Regeneron	COPD	SC	BLA; Fast Track	TBD
JDQ-443	Novartis	NSCLC	Oral	NDA	TBD
ketamine	Hope	Bipolar disorder	IV	NDA; Fast Track	TBD
latozinemab	Aldeyra	Frontotemporal dementia	IV	BLA; Breakthrough Therapy; Fast Track; Orphan Drug	TBD
lazertinib	Genosco/Janssen	NSCLC	Oral	NDA	TBD
lerodalcibep	LIB	Dyslipidemia/hypercholesterolemia; Heterozygous familial hypercholesterolemia (HeFH); Homozygous familial hypercholesterolemia (HoFH)	SC	BLA	TBD
leukocyte interleukin	Cel-Sci	SCCHN	SC	BLA; Orphan Drug	TBD
ligelizumab	Novartis	Food allergies	SC	BLA	TBD
linerixibat	GlaxoSmithKline	Primary biliary cholangitis pruritus	Oral	NDA; Orphan Drug	TBD
molgramostim	Savara	Pulmonary alveolar proteinosis	Inhaled	BLA; Breakthrough Therapy; Fast Track; Orphan Drug	TBD
navepegritide	Ascendis	Achondroplasia	SC	NDA; Orphan Drug	TBD
navitoclax	Abbvie	Myelofibrosis	Oral	NDA; Orphan Drug	TBD
nipocalimab	Janssen	Autoimmune hemolytic anemia; Myasthenia gravis	IV	BLA; Fast Track; Orphan Drug	TBD
obicetrapib	NewAmsterdam	Dyslipidemia/hypercholesterolemia	Oral	NDA	TBD
olezarsen	Akcea	Dyslipidemia/hypercholesterolemia; Familial chylomicronemia syndrome	SC	NDA; Fast Track; Orphan Drug	TBD
pabinafusp alfa	JCR	Mucopolysaccharidosis II (MPS II; Hunter Syndrome)	IV	BLA; Orphan Drug	TBD
paltusotine	Crinetics	Acromegaly	Oral	NDA; Orphan Drug	TBD
pegadricase	Swedish Orphan Biovitrum	Gout	IV	BLA	TBD
pegzilarginase	Immedica	Arginase 1 deficiency	IV	BLA; Breakthrough Therapy; Fast Track; Orphan Drug; RPD	TBD
pelabresib	Morphosys	Myelofibrosis	Oral	NDA; Fast Track; Orphan Drug	TBD
pelacarsen	Novartis	Dyslipidemia/hypercholesterolemia	SC	NDA; Fast Track	TBD
piclidenoson	Can-Fite	PSO	Oral	NDA	TBD
plozasiran	Arrowhead	Familial chylomicronemia syndrome	SC	NDA; Fast Track; Orphan Drug	TBD
ralinepag	United Therapeutics	PAH	Oral	NDA; Orphan Drug	TBD
relacorilant	Corcept	Cushing's syndrome	Oral	NDA; Orphan Drug	TBD
remibrutinib	Novartis	MS; Urticaria	Oral	NDA	TBD
resiniferatoxin	Grunenthal	Osteoarthritis pain (knee)	Intra-articular	NDA; Breakthrough Therapy	TBD
rilzabrutinib	Sanofi	ITP	Oral	NDA; Fast Track; Orphan Drug	TBD
rusfertide	Takeda	Polycythemia vera	SC	NDA; Fast Track; Orphan Drug	TBD
sebetralstat	Kalvista	HAE	Oral	NDA; Fast Track; Orphan Drug	TBD
sepiapterin	PTC	Phenylketonuria (PKU)	Oral	NDA; Orphan Drug	TBD
serplulimab	Henlius	SCLC	IV	BLA; Orphan Drug	TBD
soticlestat	Takeda	Dravet syndrome; Lennox-Gastaut syndrome	Oral	NDA; Orphan Drug	TBD
TAK-279	Takeda	PSO	Oral	NDA	TBD
tamibarotene	Syros	Myelodysplastic syndrome	Oral	NDA; Fast Track; Orphan Drug	TBD
telisotuzumab vedotin	Achieve Life Sciences	NSCLC	IV	BLA; Breakthrough Therapy	TBD
tiragolumab	Genentech	Esophageal cancer; NSCLC	IV	BLA; Breakthrough Therapy; Orphan Drug	TBD
tolebrutinib	Sanofi	MS	Oral	NDA	TBD
tiratricol	Rare Thyroid Therapeutics	Resistance to thyroid hormone type beta (RTH-b)	Oral	NDA; Fast Track; Orphan Drug; RPD	TBD
vanzacaftor/tezacaftor/deutivacaftor	Vertex	CF	Oral	NDA; Orphan Drug	TBD
vatiquinone	PTC	Friedreich's ataxia	Oral	NDA; Fast Track; Orphan Drug	TBD
venglustat	Sanofi	GM2 gangliosidoses (Tay-Sachs disease, Sandhoff disease)	Oral	NDA; Orphan Drug	TBD
vimseltinib	Deciphera	Pigmented villonodular synovitis	Oral	NDA; Fast Track	TBD
zanidatamab	Jazz	Gastric cancer	IV	BLA; Fast Track; Orphan Drug	TBD
zatolmilast	Tetra	Fragile X syndrome	Oral	NDA; Orphan Drug; RPD	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
alpelisib (Piqray®)	Novartis	Breast cancer (HER2+)	Oral	sNDA	TBD
atezolizumab (Tecentriq®)	Genentech	Breast cancer (HER2+); Breast cancer (triple-negative)	IV	sBLA	TBD
brolucizumab-dbll (Beovu®)	Novartis	Diabetic retinopathy	Intravitreal	sBLA	TBD
canakinumab (Ilaris®)	Novartis	NSCLC (adjuvant)	SC	sBLA	TBD
cabozantinib (Cabometyx®/Cometriq®)	Exelixis	Prostate cancer	Oral	sNDA	TBD
cemiplimab-rwlc (Libtayo®)	Regeneron	Melanoma	IV	sBLA; Fast Track	TBD
dupilumab (Dupixent®)	Sanofi	Bullous pemphigoid	SC	sBLA; Orphan Drug	TBD
durvalumab (Imfinzi®)	AstraZeneca	Bladder cancer (1st-line)	IV	sBLA; Breakthrough Therapy	TBD
eplontersen (Wainua™)	Ionis	Transthyretin amyloid cardiomyopathy	SC	sNDA; Fast Track; Orphan Drug	TBD
ganaxolone (Ztalmy®)	Marinus	Status epilepticus (refractory); Tuberous sclerosis complex	IV, Oral	sNDA; Orphan Drug	TBD
iptacopan (Fabhalta®)	Novartis	C3 glomerulopathy; Hemolytic uremic syndrome; IgA nephropathy (Berger's disease)	Oral	sNDA; Breakthrough Therapy; Orphan Drug; RPD	TBD
mepolizumab (Nucala®)	GlaxoSmithKline	COPD	IV, SC	sBLA	TBD
mirikizumab-mrkz (Omvoh™)	Eli Lilly	CD	IV, SC	sBLA	TBD
mitapivat (Pyrukynd®)	Agios	SCD; Thalassemia	Oral	sNDA; Orphan Drug	TBD
mosunetuzumab-axgb (Lunsumio®)	Genentech	DLBCL	SC	sBLA	TBD
obinutuzumab (Gazyva®)	Genentech	Lupus nephritis; Membranous nephropathy; SLE	IV	sBLA; Breakthrough Therapy	TBD
pozelimab (Veopoz™)	Regeneron	PNH	IV, SC	sBLA; Orphan Drug	TBD
ranibizumab port delivery system (Susvimo®)	Genentech	DME	Intravitreal implant	sBLA	TBD
satralizumab-mwge (Enspryng®)	Genentech	Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)	SC	sBLA; Orphan Drug	TBD
secukinumab (Cosentyx®)	Novartis	Giant cell arteritis; Lupus nephritis	SC	sBLA	TBD
sotorasib (Lumakras®)	Amgen	CRC	Oral	sNDA; Orphan Drug	TBD
venetoclax (Venclexta®)	Abbvie/Genenetech	Myelodysplastic syndrome; Multiple myeloma	Oral	sNDA; Breakthrough Therapy; Orphan Drug	TBD
vutrisiran (Amvuttra®)	Alnylam	Transthyretin amyloid cardiomyopathy	SC	sNDA; Orphan Drug	TBD

Traditional

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
levodopa/carbidopa patch pump	Mitsubishi Tanabe	Parkinson's disease	SC infusion	505(b)(2) NDA	Apr-Jun 2024
pivmecillinam	Utility	UTI (uncomplicated)	Oral	NDA; Priority Review; QIDP	4/24/2024
RSV pre-fusion F protein vaccine (mRNA-1345)	Moderna	RSV-related lower respiratory tract illness prevention (ages > 60 years)	IM	BLA; Breakthrough Therapy; Fast Track; Priority Review	05/10/2024
sofpironium	Botanix	Axillary hyperhidrosis (severe)	Topical	NDA	June 2024
pneumococcal polyvalent conjugate vaccine	Merck	Pneumococcal immunization (adults)	IM	BLA; Breakthrough Therapy; Priority Review	06/17/2024
ensifentrine	Verona	COPD	Inhaled	NDA	06/26/2024
insulin icodec	Novo Nordisk	T1DM; T2DM	SC	BLA	Jul-Sep 2024
naloxone (powder-based technology)	Orexo	Opioid overdose	Intranasal	505(b)(2) NDA	07/15/2024
galantamine	Alpha Cognition	Alzheimer's disease (mild-moderate)	Oral	505(b)(2) NDA	07/27/2024
carbidopa/levodopa ER	Amneal	Parkinson's disease	Oral	505(b)(2) NDA	08/08/2024
tradipitant	Vanda	Gastroparesis	Oral	NDA	09/18/2024
xanomeline/trospium	Karuna	Schizophrenia	Oral	NDA	09/26/2024
epinephrine	ARS	Anaphylaxis	Intranasal	505(b)(2) NDA; Fast Track	10/02/2024
minocycline	Journey	Rosacea	Oral	505(b)(2) NDA	11/04/2024
meningococcal vaccine (GSK3536819A)	GlaxoSmithKline	Meningococcal immunization	IM	BLA	02/14/2025
etripamil	Milestone	Paroxysmal supraventricular tachycardia	Intranasal	NDA	03/28/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
diazepam buccal film (Libervant™)	Aquestive	Seizure disorders (ages 2 to 5 years)	Oral transmucosal	sNDA; Fast Track; Orphan Drug	04/26/2024
hepatitis B vaccine (recombinant), adjuvanted (Heplisav-B®)	Dynavax	Hepatitis B immunization (adults on hemodialysis)	IM	sBLA	05/13/2024
RSV vaccine, adjuvanted (Arexvy™)	GlaxoSmithKline	RSV prevention (ages 50 to 59 years)	IM	sBLA; Fast Track; Priority Review	06/07/2024
roflumilast (Zoryve®)	Arcutis	Atopic dermatitis (adults and pediatrics ages ≥ 6 years)	Topical	sNDA	07/07/2024
vonoprazan (Takecab®)	Phathom	GERD (non-erosive)	Oral	sNDA	07/19/2024
anacaulase-bcdb (Nexobrid®)	Vericel	Burn injury (pediatrics)	Topical	sNDA; Orphan Drug	11/08/2024
semaglutide (Wegovy®)	Novo Nordisk	Chronic HFpEF	SC	sNDA	11/29/2024
tapinarof (Vtama®)	Dermavant	Atopic dermatitis (ages ≥ 2 years)	Topical	sNDA	December 2024
brexpiprazole (Rexulti®)	Otsuka	PTSD (in combination with sertraline)	Oral	sNDA	02/07/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
aceclidine	LENZ	Presbyopia	Ophthalmic	NDA	TBD
AR-15512	Aerie	DED	Ophthalmic	NDA	TBD
aroxybutynin/atomoxetine	Apnimed	Sleep apnea	Oral	NDA; Fast Track	TBD
baclofen/naltrexone/sorbitol	Pharnext	Charcot-Marie-Tooth disease	Oral	NDA	TBD
bemnifosbuvir	Atea	COVID-19	Oral	NDA; Fast Track	TBD
bentracimab	SERB	Ticagrelor (Brilinta®) reversal	IV	BLA; Breakthrough Therapy	TBD
blarcamesine	Anavex	Alzheimer's disease	Oral	NDA	TBD
brilaroxazine	Reviva	Schizophrenia	Oral	NDA	TBD
cagrilintide/semaglutide	Novo Nordisk	Obesity/overweight; T2DM	SC	NDA	TBD
carbachol/brimonidine	Visus	Presbyopia	Ophthalmic	505(b)(2) NDA	TBD
chikungunya vaccine	Bavarian Nordic	Chikungunya virus prevention	IM	BLA; Breakthrough Therapy; Fast Track	TBD
cytisinicline	Achieve Life Sciences	Smoking cessation	Oral	NDA	TBD
dengue tetravalent vaccine, live, attenuated	Takeda	Dengue fever (ages 4-60 years)	SC	BLA; Fast Track	TBD
elinzanetant	Bayer	Menopausal vasomotor symptoms	Oral	NDA	TBD
ensitrelvir fumaric acid	Shionogi	COVID-19	Oral	BLA; Fast Track	TBD
epinephrine (sublingual)	Aquestive	Anaphylaxis	SL	505(b)(2) NDA; Fast Track	TBD
esreboxetine	Axsome	Fibromyalgia	Oral	NDA	TBD
estetrol	Mithra	Menopausal vasomotor symptoms	Oral	NDA	TBD
gepotidacin	GlaxoSmithKline	Urogenital gonorrhea	Oral	NDA; QIDP	TBD
navacaprant	Neumora	MDD	Oral	NDA	TBD
orforglipron	Eli Lilly	Obesity/overweight; T2DM	Oral	NDA	TBD
paromomycin	Appili	Leishmaniasis	Topical	NDA; Orphan Drug	TBD
PL-9643	Palatin	DED	Ophthalmic	NDA	TBD
purified vero rabies vaccine (SP0087)	Sanofi	Rabies	IM	BLA	TBD
QRX003	Quoin	Congenital ichthyosis; Netherton syndrome	Topical	NDA	TBD
quadrivalent influenza mRNA vaccine (mRNA-1010)	Moderna	Seasonal influenza immunization	IM	BLA	TBD
retatrutide	Eli Lilly	Obesity/overweight; T2DM	SC	NDA	TBD
sulopenem etzadroxil/probenecid	Iterum	UTI (uncomplicated)	Oral	NDA; Fast Track; QIDP	TBD
survodutide	Boehringer Ingelheim	Obesity/overweight; T2DM	SC	NDA	TBD
suzetrigine	Vertex	Postsurgical pain	Oral	NDA; Breakthrough Therapy; Fast Track	TBD
tramiprosate	Alzheon	Alzheimer's disease	Oral	NDA; Fast Track	TBD
ulixacaltamide	Praxis	Essential tremor	Oral	NDA	TBD
VHX-896	Vanda	Bipolar disorder; Schizophrenia	Oral	NDA	TBD
XEN1101	Xenon	Partial/focal seizures	Oral	NDA	TBD
zoliflodacin	Innoviva	gonorrhea (uncomplicated)	Oral	NDA; Fast Track; QIDP	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
ibrexafungerp (Brexafemme®)	GlaxoSmithKline	Fungal infections (systemic)	Oral	sNDA; Fast Track; Orphan Drug; QIDP	TBD
lumateperone (Caplyta®)	Intra-Cellular Therapies	MDD	Oral	sNDA	TBD
phentolamine 0.75% (Ryzumvi™)	Ocuphire	Presbyopia	Ophthalmic	sNDA	TBD
roflumilast (Zoryve®)	Arcutis	PSO	Topical	sNDA	TBD
semaglutide (Ozempic®)	Novo Nordisk	Diabetic nephropathy	SC	sNDA	TBD
semaglutide (Rybelsus®)	Novo Nordisk	Obesity/overweight	Oral	sNDA	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status
apomorphine	Supernus	Parkinson's disease (continuous treatment of motor fluctuations)	SC infusion	CRL
cefepime/taniborbactam	Venatorx/Melinta	UTI (complicated)	IV	CRL
dihydroergotamine nasal powder	Shin Nippon	Migraine (acute treatment)	Intranasal	CRL
odronextamab	Pfizer	DLBCL (R/R); Follicular lymphoma (R/R)	IV	CRL
roluperidone	Minerva	Schizophrenia (negative symptoms)	Oral	CRL
scopolamine	Repurposed Therapeutics	Motion sickness	Intranasal	CRL
tasimelteon (Hetlioz®)	Vanda	Jet lag disorder	Oral	CRL
tesamorelin (Egrifta®) high concentration	Theratechnologies	HIV lipodystrophy	SC	CRL

5-FU 5-Fluorouracil

6MWD 6 Minute Walking Distance

6MWT 6 Minute Walking Test

ABSSSI Acute Bacterial Skin and Skin Structure Infection

ACC American College of Cardiology

ACEI Angiotensin-Converting Enzyme Inhibitor

ACR20 American College of Rheumatology 20% Improvement

ACR50 American College of Rheumatology 50% Improvement

ACR70 American College of Rheumatology 70% Improvement

ADC Antibody-Drug Conjugate

ADHD Attention Deficit Hyperactivity Disorder

ADL Activities of Daily Living

ALK Anaplastic Lymphoma Kinase

ALK+ Anaplastic Lymphoma Kinase-positive

ALL Acute Lymphoblastic Leukemia

ALS Amyotrophic Lateral Sclerosis

ALSFRS-R Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised

ALT Alanine Transaminase

AMD Age-Related Macular Degeneration

AML Acute Myeloid Leukemia

ANCA Antineutrophil Cytoplasmic Antibodies

ARB Angiotensin II Receptor Blocker

ARNI Angiotensin Receptor II Blocker – Neprilysin Inhibitor

AS Ankylosing Spondylitis

ASCVD Atherosclerotic Cardiovascular Disease

AST Aspartate Aminotransferase

BCG Bacillus Calmette-Guérin

BCL-1

BCVA Best Corrected Visual Acuity

BLA Biologics License Application

BMI Body Mass Index

BMT Bone Marrow Transplant

BP Blood Pressure

BPH Benign Prostatic Hyperplasia

BRAF V-Raf Murine Sarcoma Viral Oncogene Homolog B1

BTK Bruton’s Tyrosine Kinase

BSA Body Surface Area

BsUFA Biosimilar User Fee Act

CABP Community Acquired Bacterial Pneumonia

CAP Community Acquired Pneumonia

CAR T Chimeric Antigen Receptor T-Cell

CD Crohn's Disease

CD3 Cluster of Differentiate 3

CD19 Cluster of Differentiate 19

CD20 Cluster of Differentiate 20

CD38 Cluster of Differentiate 38

CD79b Cluster of Differentiate 79b

CDC Centers for Disease Control and Prevention

CF Cystic Fibrosis

CHF Congestive Heart Failure

CI Confidence Interval

CKD Chronic Kidney Disease

CLL Chronic Lymphocytic Leukemia

CML Chronic Myeloid Leukemia

CMS Centers for Medicare & Medicaid Services

CNS Central Nervous System

COPD Chronic Obstructive Pulmonary Disease

COVID-19 Coronavirus Disease 2019

CRC Colorectal Cancer

CRL Complete Response Letter

CRR Complete Response Rate

CRS Cytokine Release Syndrome

CSF Colony Stimulating Factor

CTLA-4 Cytotoxic T-Lymphocyte-Associated Protein 4

CV Cardiovascular

CVD Cardiovascular Disease

CYP3A4 Cytochrome P-450 3A4

CYP450 Cytochrome P-450

DAS28-CRP Disease Activity Score-28 with C Reactive Protein

DBP Diastolic Blood Pressure

DCR Disease Control Rate

DEA Drug Enforcement Administration

DED Dry Eye Disease

DLBCL Diffuse Large B Cell Lymphoma

DMARD Disease Modifying Antirheumatic Drug

DMD Duchenne Muscular Dystrophy

DME Diabetic Macular Edema

dMMR DNA mismatch repair

DMT Disease Modifying Therapy

DNA Deoxyribonucleic Acid

DOR Duration of Response

DPP-4 Dipeptidyl Peptidase 4

DR Delayed-Release

DSM-5 Diagnostic and Statistical Manual of Mental Disorders, 5th edition

EASI-75 Eczema Area and Severity Index ≥ 75% Reduction

ECOG Eastern Cooperative Oncology Group

EDSS Expanded Disability Status Scale

eGFR estimated Glomerular Filtration Rate

EGFR Epidermal Growth Factor Receptor

ER Extended-Release

ERA Endothelin Receptor Agonist

ESA Erythropoietin Stimulating Agent

ESRD End-Stage Renal Disease

EUA Emergency Use Authorization

FDA Food and Drug Administration

FEV1 Force Expiratory Volume in 1 Second

FH Familial Hypercholesterolemia

FLT3 FMS-Like Tyrosine Kinase-3

FMS Feline McDonough Sarcoma

FVC Forced Vital Capacity

GABA-A Gamma-Aminobutyric Acid Receptor Type A

G-CSF Granulocyte Colony Stimulating Factor

GERD Gastroesophageal Reflux Disease

GGT Gamma-Glutamyl Transferase

GI Gastrointestinal

GIST Gastrointestinal Stromal Tumor

GLP-1RA Glucagon-Like Peptide-1 Receptor Agonist

GM-CSF Granulocyte-Macrophage Colony Stimulating Factor

GVHD Graft Versus Host Disease

H Half

HAE Hereditary Angioedema

HAM-A Hamilton Anxiety Rating Scale

HAM-D Hamilton Depression Rating Scale

HAMD-17 Hamilton Depression Rating Scale

HAP Healthcare-Associated Pneumonia

Hb Hemoglobin

HbA1c Hemoglobin A1c

HBV Hepatitis B Virus

HCC Hepatocellular Carcinoma

HCP Healthcare Professional

HCV Hepatitis C Virus

HDRS-17 Hamilton Depression Rating Scale

HER Human Epidermal Growth Factor Receptor

HER2 Human Epidermal Growth Factor Receptor 2

HER2- Human Epidermal Growth Factor Receptor 2-negative

HER2+ Human Epidermal Growth Factor Receptor 2-positive

HF Heart Failure

HFA Hydrofluoroalkane

HFpEF Heart Failure with preserved Ejection Fraction

HFrEF Heart Failure with reduced Ejection Fraction

HIT Heparin Induced Thrombocytopenia

HIV Human Immunodeficiency Virus

HIV-1 Human Immunodeficiency Virus-1

HR Hazard Ratio

HR+ Hormone Receptor-positive

HS Hidradenitis Suppurativa

HSCT Hematopoietic Stem Cell Transplant

HSV Herpes Simplex Virus

HTN Hypertension

IBS Irritable Bowel Syndrome

IBS-C Irritable Bowel Syndrome, Constipation Predominant

ICER Institute for Clinical and Economic Review

ICS Inhaled Corticosteroid

IDH Isocitrate Dehydrogenase

IGA Investigator's Global Assessment

IgG Immunoglobulin G

IgG1 Immunoglobulin G1

IHC Immunohistochemistry

IL-4 Interleukin-4

IL-5 Interleukin-5

IL-8 Interleukin-8

IL-12 Interleukin-12

IL-13 Interleukin-13

IL-17 Interleukin-17

IL-23 Interleukin-23

IL-31 Interleukin-31

IM Intramuscular

IR Immediate-Release

IRB Institutional Review Board

ITP Immune Thrombocytopenic Purpura

ITT Intent-To-Treat

IV Intravenous

JAK Janus Kinase Inhibitor

JIA Juvenile Idiopathic Arthritis

KIT c-KIT Proto-Oncogene

KMT2A Lysine (K)-Specific Methyltransferase 2A

LABA Long-Acting Beta Agonist

LAMA Long-Acting Muscarinic Antagonist

LDL-C Low-Density Lipoprotein Cholesterol

LPAD Limited Population Pathway for Antibacterial and Antifungal Drugs

LS Least Square

LVEF Left Ventricular Ejection Fraction

mAb Monoclonal Antibody

MACE Major Adverse Cardiovascular Events

MADRS Montgomery – Åsberg Depression Rating Scale

MDD Major Depressive Disorder

MDI Metered Dose Inhaler

MDR Multi-Drug Resistant

MECP2 Methyl-CpG Binding Protein 2

MEK Mitogen-Activated Extracellular Signal-Regulated Kinase

MI Myocardial Infarction

mITT modified Intent-To-Treat

MRI Magnetic Resonance Imaging

MRSA Methicillin-Resistant Staphylococcus Aureus

MS Multiple Sclerosis

MSI-H Microsatellite Instability-High

N/A Not Applicable

NAFLD Nonalcoholic Fatty Liver Disease

NASH Non-Alcoholic Steatohepatitis

NCCN National Comprehensive Cancer Network

NCT National Clinical Trials

NDA New Drug Application

NHL Non-Hodgkin Lymphoma

NIH National Institutes of Health

NRAS Neuroblastoma RAS Proto-Oncogene

NSAID Non-Steroidal Anti-Inflammatory Drug

NSCLC Non-Small Cell Lung Cancer

NTRK Neurotrophic Tyrosine Receptor Kinase

NYHA New York Heart Association

ODT Orally Disintegrating Tablet

OR Odds Ratio

ORR Objective Response Rate

OS Overall Survival

OTC Over-the-Counter

PAD Peripheral Arterial Disease

PAH Pulmonary Arterial Hypertension

PARP Poly (ADP-Ribose) Polymerase

PAS Prior Approval Supplement

PASI Psoriasis Area and Severity Index

PASI 50 Psoriasis Area and Severity Index 50% Reduction

PASI 75 Psoriasis Area and Severity Index 75% Reduction

PASI 90 Psoriasis Area and Severity Index 90% Reduction

PASI 100 Psoriasis Area and Severity Index 100% Reduction

PCI Percutaneous Coronary Intervention

PCSK9 Proprotein Convertase Subtilisin Kexin 9

PD-1 Programmed Death Protein 1

PD-L1 Programmed Death-Ligand 1

PDE3 Phosphodiesterase 3

PDE4 Phosphodiesterase 4

PDE5 Phosphodiesterase 5

PDUFA Prescription Drug User Fee Application

PFS Progression-Free Survival

PGA Physician Global Assessment

PHI Primary Humoral Immunodeficiency

PI3K Phosphatidylinositol-3-kinase

PNH Paroxysmal Nocturnal Hemoglobinuria

PsA Psoriatic Arthritis

PSO Plaque Psoriasis

PTCA Percutaneous Transluminal Coronary Angioplasty

PTSD Post-Traumatic Stress Disorder

Q Quarter

QIDP Qualified Infectious Diseases Product

QOL Quality of Life

R/R Relapsed or Refractory

R-CHOP Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

RA Rheumatoid Arthritis

RAS Ras Protein Superfamily

RBC Red Blood Cell

RCC Renal Cell Carcinoma

REMS Risk Evaluation and Mitigation Strategy

RMAT Regenerative Medicine Advanced Therapy

RNA Ribonucleic Acid

ROS1 ROS Proto-Oncogene 1

RPD Rare Pediatric Disease

RRR Relative Risk Reduction

RSV Respiratory Syncytial Virus

RTOR Real-Time Oncology Review

RVO Retinal Vein Occlusion

SARS-CoV-2 Severe Acute Respiratory Syndrome-Associated Coronavirus-2

sBLA supplemental Biologics License Application

SBP Systolic Blood Pressure

SC Subcutaneous

SCCHN Squamous Cell Cancer of the Head and Neck

SCD Sickle Cell Disease

SCLC Small Cell Lung Cancer

SCT Stem Cell Transplant

SGLT2 Sodium-Glucose Co-Transporter 2

SL Sublingual

SLE Systemic Lupus Erythematosus

SLL Small Lymphocytic Lymphoma

sNDA supplemental New Drug Application

SNRI Serotonin and Norepinephrine Reuptake Inhibitor

SOC Standard of Care

SOD-1 Superoxide Dismutase - Type 1

sPGA static Physician Global Assessment

SR Sustained-Release

SSRI Selective Serotonin Reuptake Inhibitor

SSSI Skin and Skin Structure Infection

T1DM Type 1 Diabetes Mellitus

T2DM Type 2 Diabetes Mellitus

TBD To Be Determined

TEAE Treatment-Emergent Adverse Event

TKI Tyrosine Kinase Inhibitor

TNBC Triple Negative Breast Cancer

TNF Tumor Necrosis Factor

TNFα Tumor Necrosis Factor-alpha

UA Unstable Angina

UC Ulcerative Colitis

ULN Upper Limit of Normal

U.S. United States

UTI Urinary Tract Infection

VAS Visual Analog Scale

VEGF Vascular Endothelial Growth Factor

VTE Venous Thromboembolism

WBC White Blood Cell

WHO World Health Organization

XR Extended-Release