Quarterly Drug Pipeline: July 2024

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 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 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 22 novel drugs, roughly 21% fewer approvals compared to 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 Alzheimer’s disease, new option for chronic obstructive pulmonary disease (COPD), a new injectable for paroxysmal nocturnal hemoglobinuria (PNH), and a new therapy for primary biliary cholangitis (PBC). Moreover, first-time biosimilars to Eylea®, the first interchangeable biosimilar to eculizumab (Soliris®), and a respiratory syncytial virus (RSV) vaccine built on an mRNA platform were approved. 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 (73%) and for Orphan Drugs (35%) continue to grow for agents with applications submitted to the FDA. Three agents are seeking FDA’s Accelerated Approval.

Notable FDA decisions expected for third quarter 2024 include several firsts:

First psychedelic-assisted therapy for post-traumatic stress disorder (PTSD)
First SC version of Ocrevus®
First new options for Niemann-Pick disease type C
First new mechanism for gastroparesis
First new mechanism to treat schizophrenia in decades

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.

acoramidis oral

Manufacturer: Bridgebio / AstraZeneca

Proposed indications

Transthyretin amyloid cardiomyopathy (ATTR-CM)

Clinical overview

Mechanism of action
Acoramidis is a tetrameric transthyretin (TTR) stabilizer.

Clinical trials
The randomized, double-blind, placebo-controlled, phase 3 ATTRibute-CM trial (NCT03860935) evaluated acoramidis in 632 patients with ATTR-CM and clinical heart failure. There were two co-primary endpoints. The first co-primary endpoint reported no statistically significant difference in the change in 6MWD with acoramidis compared to placebo (LS mean change, -26.51 meters versus -24.54 meters, respectively) at 12 months. The second co-primary endpoint was a four-step hierarchical analysis including (in order) death from any cause, CV-related hospitalization, the change from baseline in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6MWD after 30 months of treatment, which produced a win ratio of 1.8 (p<0.001), favoring acoramidis over placebo. In addition, the study showed that acoramidis significantly increased serum TTR levels at day 28 (p<0.001), which remained stable through month 30; an increase in serum TTR is associated with improved clinical outcomes. Acoramidis also demonstrated about a 25% relative risk reduction (RRR) in death from any cause and a 50% RRR in CV-related hospitalizations compared to placebo at 30 months. Similar safety profiles were observed with acoramidis and placebo.

Dosage and administration
In the ATTRibute-CM trial, acoramidis 800 mg was administered orally twice daily.

Place in therapy

ATTR-CM results from the misfolding and accumulation of the tetrameric protein TTR into the extracellular space of the myocardium, which leads to progressive thickening of the ventricular wall and stiffening of the heart. Life expectancy after ATTR-CM diagnosis is about 2 to 6 years. There are two types of ATTR-CM. Wild-type ATTR-CM is due to misfolded wild-type (normal) TTR, the mechanism for which is unclear. Hereditary ATTR-CM is due to mutations in the TTR gene, which predisposes TTR to misfold. Based on limited data, an estimated 5,000 to 7,000 new cases of ATTR-CM are diagnosed each year in the U.S.; however, estimates are increasing due to advancements in diagnostic methods. ATTR-CM typically presents in individuals ≥ 60 years of age. Patients with ATTR-CM often have symptoms of chronic heart failure.

TTR is synthesized by the liver, and liver transplantation is the gold standard for treating transthyretin-related amyloidosis (ATTR). Multi-organ transplantation (heart, liver, and kidney) has been successful in slowing the natural course of the disease. Tafamidis/tafamidis meglumine (Vyndaqel®, Vyndamax®) is a TTR stabilizer approved by the FDA to treat ATTR-CM. The oral NSAID diflunisal may also stabilize TTR but is rarely used off-label for ATTR-CM due to poor tolerance and uncertain efficacy. Notably, standard treatments for CV disease such as beta-blockers, ACEIs, ARBs, diuretics or digoxin can worsen ATTR-CM symptoms.

Acoramidis leads to near-complete TTR stabilization with improved potency and stabilization compared to tafamidis. The ATTRibute-CM trial reported mixed data for acoramidis compared to placebo. While acoramidis did not significantly improve 6MWD at 12 months, significant benefit was demonstrated at 30 months in a hierarchical analysis that included all-cause mortality, CV-related hospitalization, NT-proBNP, and 6MWD. Notably, in its pivotal trial, tafamidis led to a 30% RRR in death from any cause and a 32% RRR in CV-related hospitalization compared to placebo at 30 months. If approved, acoramidis will be the second medication in the U.S. indicated to treat ATTR-CM and will directly compete with tafamidis agents.

FDA approval timeline

November 29, 2024

FDA Designations: Orphan Drug

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$16	$110	$293	$591	$866

arimoclomol oral

Manufacturer: Zevra

Proposed indications
Niemann-Pick disease type C (NPC)

Clinical overview

Mechanism of action
Arimoclomol preserves cellular function and prevents cell death in cells experiencing lysosomal stress. It does this by amplifying the natural response to cellular stress through production of heat shock proteins (HSPs) that prevent protein misfolding.

Clinical trials
A 12-month, double-blind, phase 2/3 trial (NPC-002) evaluated arimoclomol for the treatment of NPC in addition to routine clinical care; stable miglustat therapy was allowed. Enrolled patients (n=50) were 2 to 18 years of age and were able to walk independently or with assistance. The primary endpoint was change from baseline to 12 months in NPC severity as measured by the 5-domain (5D)-NPC Clinical Severity Scale (NPCCSS) score, which includes parameters for ambulation, cognition, fine motor skills, speech, and swallowing (range, 0 to 25) with higher scores indicating greater impairment. The study demonstrated a 65% relative reduction in annual disease progression with arimoclomol based on the 5D-NPCCSS score (difference versus placebo, -1.4 point; p=0.046). Among patients also receiving miglustat, the difference in mean change in 5D-NPCCSS from baseline to 12 months with arimoclomol compared to placebo was -2.06 points (p=0.006). At 12 months, 50% and 37.5% of patients in the arimoclomol and placebo groups, respectively, had stable or improved disease (responders) (p=0.546). In addition, there was no significant difference between arimoclomol and placebo in the secondary endpoint of change from baseline to 12 months in the Scale for Assessment and Rating of Ataxia (SARA) score (LS mean difference, 0.28 points; p=0.79). Arimoclomol was well tolerated. Upper respiratory tract infection, decreased weight, and urticaria were reported more frequently with arimoclomol than placebo.

Interim data from an open-label extension (OLE) trial, in which all patients received arimoclomol, reported sustained reduction in NPC progression through 36 months. In addition, early treatment initiation with arimoclomol resulted in greater benefit compared to delayed start (in patients who switched from placebo to arimoclomol at the start of the OLE trial).

Dosage and administration
In the clinical trials, a weight-based dose (93 to 372 mg/day) of arimoclomol was administered by mouth or by feeding tube three times per day.

FDA approval timeline

September 21, 2024
The FDA’s Genetic Metabolic Diseases Advisory Committee will review arimoclomol for the treatment of Niemann-Pick disease type C on August 2, 2024.

FDA designations: Breakthrough Therapy, Fast Track, Orphan Drug, RPD

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$2	$38	$62	$80	$95

N-acetyl-L-leucine oral

Manufacturer: Intrabio

Proposed indications
Niemann-Pick disease type C (NPC)

Clinical overview

N-acetyl-L-leucine (NALL) is a modified, acetylated derivative of the natural essential amino acid leucine that normalizes energy production, improves lysosomal function and cellular signaling, and mitigates neuronal inflammation.

A double-blind, placebo-controlled, crossover trial (NCT05163288) evaluated NALL in 60 patients ≥ 4 years of age with NPC. Enrolled patients had mild to severe NPC symptoms correlating to a Scale for the Assessment and Rating of Ataxia (SARA) score between 7 to 34 at baseline; lower SARA scores indicate better neurologic status. Patients were randomized to NALL or placebo for 12 weeks, followed by alternate treatment for 12 weeks. The primary endpoint was mean change from baseline to week 12 in the SARA total score; however, the FDA requested use of a modified SARA (mSARA) score, which did not include stance and sitting as part of the assessment. After 12 weeks, the mean change from baseline in the SARA total score was -1.97 points with NALL and -0.6 points with (LS mean difference, -1.28 points; p<0.001). Based on the mSARA, the LS mean difference after NALL and after placebo therapies was -0.96 point (p-value not reported). Exploratory data for NPCCSS (scale, 0 to 54) showed a difference in change from baseline between NALL and placebo of -0.5 point. The difference in change in the Clinical Global Impression of Improvement (CGI-I) after NALL and after placebo therapies was -0.6. No serious TEAEs occurred with NALL. One case of anal incontinence, restless legs, and rosacea were reported as transient TEAEs associated with NALL.

Dosage and administration
In the clinical trial, NALL was administered orally two to three times per day. Patients 4 to 12 years of age received 2 g to 4 g per day and those ≥ 13 years of age received 4 g per day.

Place in therapy

NPC is a rare, inherited, lysosomal storage disorder with an estimated incidence of 1 per 100,000 live births. It is caused by mutations in the NPC1 gene (95% of cases) or NPC2 gene (5% of cases) that result in dysfunctional NPC proteins giving rise to abnormal accumulation of lipids in tissues and organs, including the brain. Signs and symptoms of NPC include hepatosplenomegaly as well as neurologic manifestations, such as impaired motor function, cognitive function, swallowing and speech. Clinical presentation and disease progression depend on the patient’s age when neurological symptoms first appear, with younger age associated with more aggressive disease.

There is no cure for NPC. Miglustat has been used off-label in the U.S. It inhibits synthesis of glycolipids and has demonstrated slowing of disease progression in clinical trials. The use of miglustat may be considered in patients with mild to moderate neurologic, psychiatric, or cognitive manifestations, ideally starting use at the time of onset of neurologic manifestations.

If approved, arimoclomol and NALL would be the first agents FDA-approved for the treatment of NPC, a disorder with high unmet medical need. In clinical trials, both oral agents demonstrated improvement in neurologic status but used different tools to evaluate symptoms of cerebellar ataxia. Phase 3 trials for arimoclomol displayed long-term data with reduction in disease progression for up to 3 years based on the validated 5D-NPCCSS score, whereas improvement in neurologic status by NALL was revealed in results from a 12-week study based on the SARA score, which is validated for evaluating effects on spinocerebellar ataxia, but not for NPC. Moreover, data revealed neurologic symptoms improved during treatment with NALL; although, neurologic status declined when the agent was stopped. Notably, there is no validated biomarker for NPC or surrogate endpoint that indicates clinical improvement.

Intrathecal and IV formulations of cyclodextrin are also in phase 3 trials for NPC.

FDA approval timeline

September 24, 2024

FDA designations: Fast Track, Orphan Drug, Priority Review, RPD

Financial forecast (reported in millions)

The financial forecast for NALL is not currently available.

axatilimab IV

Manufacturer: Syndax

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	$1	$32	$72	$91	$116

eladocagene exuparvovec (Upstaza™) intraputaminal

Manufacturer: PTC Therapeutics

Proposed indications

Aromatic L-amino acid decarboxylase (AADC) deficiency

Clinical overview

Mechanism of action
Eladocagene exuparvovec is a recombinant adeno-associated virus serotype 2 (AAV2)-based gene therapy. It delivers a functional dopa decarboxylase (DDC) gene to increase AADC enzyme levels and restore dopamine production.

Clinical trials
In a study conducted in Taiwan, 26 patients were enrolled in three consecutive trials (including compassionate use, phase 1/2, and phase 2b) with similar treatment protocols and completed follow-up evaluations at 1-year. The mean age at the time of treatment was 4.1 years (range, 1.7 to 8.5 years). The mean duration of follow up was 5.4 years of age (range, 2 to 10.2 years of age). Motor ability was evaluated using the Peabody Developmental Motor Scales–Second Edition (PDMS-2) that assesses fine motor function and the Alberta Infant Motor Scale (AIMS) that assesses gross motor skills. Eladocagene exuparvovec led to a significant increase in the PDMS-2 score from baseline (10.4 ± 5.4) to 1 year (80.5 ± 43.4; n=25), 2 years (114.5 ± 55.2; n=22), and 5 years (116.1 ± 59.8; n=11) after the dose (p<0.01 for each). Likewise, the AIMS score significantly increased from baseline (1.8 ± 1.8) at 1 year (18.8 ± 11), 2 years (26.9 ± 15.5), and 5 years (24.5 ± 15) after the dose (p<0.001 for each). Secondary endpoints included change in the levels of the dopamine and serotonin metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), in the cerebrospinal fluid after 12 months; significant increases in HVA were reported (p<0.001) but not in 5-HIAA. While improvements were observed in all patients who received eladocagene exuparvovec, greater improvement was associated with treatment at a younger age. Adverse events reported include post-surgery complications such as cerebrospinal fluid leakage, which were managed with SOC. No treatment-related brain injuries occurred. Mild to moderate dyskinesia was reported in most patients and resolved within a few months.

Dosage and administration
Eladocagene exuparvovec is administered as a one-time dose via intraputaminal (base of forebrain) infusion.

Place in therapy

AADC deficiency is an ultra-rare, autosomal recessive, neurometabolic disorder. It is caused by a mutation in the DDC gene that encodes the production of AADC, an enzyme that plays a key role in the production of serotonin, dopamine, epinephrine, and norepinephrine. Impairment of these neurotransmitters leads to developmental delays, intellectual disabilities, and life-long movement disorders and autonomic nervous system dysfunction. Symptom onset usually occurs within the first six months of life. Approximately 150 to 350 cases have been identified in the literature, with it reported more often in certain Asian populations (Taiwanese, Japanese, Chinese). Symptom severity can range from relatively mild to very severe due to a broad phenotypic spectrum for the disease. Individuals with AADC deficiency are at an increased risk of early death due to complications such as infection or an acute cardiorespiratory event. Many who are affected do not live through childhood, but those with milder disease may reach adulthood.

There is no cure for AADC deficiency. Medications used to treat the condition include selective dopamine agonists, monoamine oxidase inhibitors (MAOIs) and pyridoxine. However, treatment response varies greatly among affected individuals. Agents for symptom management, such as anticholinergics, benzodiazepines, alpha-adrenoreceptor blockers and melatonin may also be used.

If approved, the one-time gene therapy, eladocagene exuparvovec, will be the first treatment to target the underlying cause of AADC deficiency. In clinical trials, significant and durable improvement in motor skills was reported.

FDA approval timeline

November 13, 2024

FDA Designations: Orphan Drug, Priority Review, RPD, seeking Accelerated Approval

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$3	$19	$33	$46	$57

garadacimab SC

Manufacturer: CSL

Proposed indications

Prophylactic treatment for hereditary angioedema (HAE)

Clinical overview

Mechanism of action
Garadacimab is a recombinant monoclonal antibody that targets activated factor XIIa (FXIIa). It inhibits the kallikrein-kinin cascade early in the cascade.

Clinical trials
The 6-month, double-blind, placebo-controlled VANGUARD trial (NCT04656418) evaluated garadacimab as a prophylactic treatment in patients ages ≥ 12 years with type I or type II HAE (n=65). During the treatment period, garadacimab reduced the number of HAE attacks per month (primary endpoint) by 87% compared with placebo (0.27 versus 2.01, respectively; p<0.0001). The median number of HAE attacks per month was zero for garadacimab and 1.35 for placebo. The most common TEAEs reported were upper-respiratory tract infections, nasopharyngitis and headaches. No increased risk of bleeding or thromboembolic events was observed. The extension phase of the VANGUARD trial is ongoing.

Dosage and administration
In the clinical trial, garadacimab was administered SC as a 400 mg (two 200 mg injections) loading dose, followed by five additional 200 mg SC self-administered (or caregiver-administered) doses once monthly.

Place in therapy

HAE is a rare, dominant autosomal genetic disorder that affects approximately 6,000 individuals in the U.S. Patients with HAE have low levels of endogenous or functional C1 esterase inhibitor (C1-INH). There are two types of C1-INH deficient HAE. Type I, in which the body does not produce enough C1-INH, accounts for about 85% of cases. Type II HAE is caused by the presence of normal or high levels of a dysfunctional C1-INH. HAE is characterized by recurrent episodes of nonpruritic, nonpitting, SC or submucosal edema involving the skin or mucosal tissues of the upper respiratory and GI tracts. Although swelling can resolve spontaneously in several days, without treatment, laryngeal edema can be fatal, and the pain of GI attacks can be incapacitating. Symptoms may begin as early as 2 years of age and persist throughout life with unpredictable severity and frequency of attacks. It is thought that minor trauma and stress can lead to an attack; although, many attacks occur without any apparent trigger.

The IV-administered C1-INH (Cinryze®), SC-administered C1-INH (Haegarda®), SC-administered plasma kallikrein inhibitor lanadelumab-flyo (Takhzyro®), and orally administered plasma kallikrein inhibitor berotralstat (Orladeyo®) are available for long-term HAE prophylaxis in children and adults. If approved, once monthly SC garadacimab, which has the potential to be administered by the patient or caregiver, would become the first treatment for HAE in the U.S. that targets activated FXIIa. It will compete with Haegarda® and Takhzyro® that are self- or caregiver-administered every 2 weeks; Takhzyro’s® dosing interval can be extended to every 4 weeks in patients who are well-controlled for 6 months.

FDA approval timeline

October to December 2024

FDA Designations: Fast Track, Orphan Drug

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$28	$64	$101	$138	$175

govorestat oral

Manufacturer: Applied Therapeutics

Proposed indications

Classic galactosemia

Clinical overview

Mechanism of action
Govorestat is an aldose reductase inhibitor (ARI) that penetrates the CNS.

Clinical trials

The placebo-controlled, phase 2/3, ACTION-Galactosemia Kids study (NCT04902781) evaluated govorestat in 47 patients ages 2 to 17 years with galactosemia. The primary endpoint was the Global Statistical Test, a composite sum of change of the following measures: Oral and Written Language Scales-Second Edition (OWLS-2) Oral Expression (OE), OWLS-2 Listening Comprehension (LC), Behavior Assessment System for Children-Third Edition (BASC-3) Activities of Daily Living (ADL), and BASC-3 Behavior Symptoms Index (BSI). While the primary endpoint was not met (p=0.103), there was systematic improvement over time for the overall primary endpoint. Govorestat demonstrated improvement in galactitol biomarker levels and clinically meaningful improvements in activities of daily living, behavior, cognition, adaptive skills, and tremor. Statistically significant improvements were seen in behavior and activities of daily living (p=0.0205) and tremor (p=0.0428, at 18 months). Govorestat was well tolerated. The study includes an open-label extension as an active treatment extension for patients who received placebo treatment.

A long-term open-label study in adults with galactosemia is ongoing.

Dosage and administration
In the clinical trials, govorestat was given orally. In Part A, govorestat was administered at 5 mg/kg for all ages. Part B administered the drug at an optimum dose determined in Part A.

Place in therapy

Classic galactosemia is a rare, genetic disorder caused by mutations in the GALT gene that leads to a deficiency of the galactose-1-phosphate uridylyl transferase (GALT) enzyme. Patients lack the ability to convert galactose to glucose, which leads to the accumulation of the toxic metabolite galactitol in tissues and organs. Newborns are screened for classic galactosemia as early diagnosis and a lactose-and galactose-free diet is imperative to avoid profound intellectual disability, liver failure and death within days to weeks from birth. However, since galactose is produced by the body, long-term complications will still occur even with a restricted diet. Classic galactosemia is estimated to affect 1 in 16,000 to 1 in 48,000 births.

There is currently no pharmacologic treatment for classic galactosemia. If approved, govorestat will be the only medication available to treat the disease. In clinical trials, while the composite primary endpoint was not met, clinically meaningful improvements, including in activities of daily living, behavior, cognition, adaptive skills, and tremor were experienced with govorestat.

Govorestat is also in phase 3 trials for sorbitol dehydrogenase (SORD) deficiency.

FDA approval timeline

November 28, 2024

An FDA advisory committee meeting to discuss the application is planned.

FDA designations: Fast Track, Orphan Drug, Priority Review, RPD

Financial forecast (reported in millions)

The financial forecast for govorestat is not currently available.

obecabtagene autoleucel IV

Manufacturer: Autolus

Proposed indications

Relapsed/refractory (R/R) adult B-cell acute lymphoblastic leukemia (ALL)

Clinical overview

Mechanism of action
Obecabtagene autoleucel (obe-cel) is an autologous CD19-directed CAR T therapy.

Clinical trials
The ongoing, open-label, single-arm, phase 1b/2 FELIX trial (NCT04404660) evaluated obe-cel in adults with R/R B-cell ALL. The study included 126 patients with morphological disease ≥ 5% bone marrow (BM) blasts (cohort A), or in second or later complete remission (CR)/CR with incomplete hematologic recovery (CRi) with measurable residual disease (MRD) (cohort B), or with isolated extramedullary disease (EMD) (cohort C). Philadelphia chromosome-positive (Ph+) B-cell ALL was reported in 27% of patients. Enrollees had a median of 2 (range, 1 to 6) prior lines of therapy. Topline results of pooled data from all three cohorts revealed, at a median follow-up of 11 months (range, 0.9 to 30.6 months), CR/CRi (primary endpoint) occurred in 77% of patients who received obe-cel, with CR in 57% of patients. Among evaluable responders, 96% were considered to have MRD-negative status. The median DOR had not been reached. Grade ≥ 3 CRS occurred in 2.4% of patients, and grade ≥ 3 immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 7.1% of patients.

Dosage and administration
In the FELIX trial, after pre-conditioning with chemotherapy (cyclophosphamide and fludarabine), obe-cel was administered IV at a target dose of 410 × 106 cells as a split dose on day 1 and day 10 (± 2 days).

Place in therapy

In ALL, the bone marrow produces an excessive number of lymphocytes. Nearly 30% of patients with ALL are diagnosed at ≥ 45 years of age and nearly 14% are diagnosed at ≥ 65 years of age. In addition, about 75% of adult cases develop from B cell lineage, and 25% emerge from T cell precursors. Risk factors for developing ALL in adulthood include age > 70 years, prior treatment with chemotherapy or radiation therapy, environmental radiation exposure, and certain genetic conditions (e.g., Down syndrome). In general, prognosis of ALL decreases with age, with a 5-year survival rate of 20% to 40% in adults.

Pharmacologic agents that target B-cell surface antigens have demonstrated improved response in R/R B-cell ALL. This includes select tyrosine kinase inhibitors (in Ph+ B-cell ALL only; CR/CRi rates, 42%-47%), a bispecific CD19-directed CD3 T-cell engager (blinatumomab [Blincyto®]; CR rate, 43%), an anti-CD22 monoclonal antibody (inotuzumab ozogamicin [Besponsa®]; CR/CRi rate, 78.4%), and CD19-directed CAR T cell therapies (brexucabtagene autoleucel [Tecartus®] and tisagenlecleucel [Kymriah®]; CR rate, 69%-81%). Allogeneic HCT may also be considered in eligible patients. Choice of treatment should be individualized based on the presence or absence of target antigen (CD19 and CD22), prior exposure to one of these agents, patient immune status, and disease burden.

HCT is currently the only treatment considered a cure for R/R ALL, but many patients are not eligible for HCT. Notably, the CAR T cell therapies have served as a bridge, allowing patients with initial poor remission status to become eligible for HCT; however, high rates of toxicities, including CRS and neurologic toxicities, have complicated their use.

Obe-cel is a CAR T cell therapy that was created with a fast target binding off-rate that minimizes excessive activation of the programmed T cells. Clinical trials have demonstrated that its fast off-rate profile reduces toxicity and T cell exhaustion, leading to improved persistence and high levels of durable remissions compared to existing CD19-directed CAR T cell therapies in adults with R/R ALL. If approved, obe-cel will compete with the other CD19 CAR T cell therapies, Kymriah® and Tecartus®, in the adult R/R B-cell ALL setting. While all three CAR T therapies demonstrate high response rates, obe-cel’s improved safety profile may differentiate it from the other agents. In non-comparative clinical trials in patients with ALL, the rates of grade ≥ 3 CRS were 2.4% with obe-cel, 26% with Tecartus®, and 48% with Kymriah®. Likewise, serious neurologic toxicities were reported at rates of 7.1% with obe-cel, 35% with Tecartus®, and 22% with Kymriah®.

FDA approval timeline

November 16, 2024

DA designations: Orphan Drug, RMAT

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$3	$56	$83	$121	$129

tradipitant oral

Manufacturer: Vanda / Eli Lilly

Proposed indications

Gastroparesis (GP)

Clinical overview

Mechanism of action
Tradipitant is a neurokinin receptor 1 (NK-1R) antagonist and may treat gastroparesis by acting centrally in the nausea-vomiting centers of the brain and peripherally in the smooth muscle of the intestines.

Clinical trials

A double-blind, placebo-controlled, phase 3 trial (NCT04028492) assessed the efficacy of tradipitant in relieving GP symptoms in patients with idiopathic and diabetic GP. The primary endpoint was the change from baseline to week 12 (days 78 to 84) in average nausea severity as measured by the Gastroparesis Core Symptom Daily Diary (GCSDD) in the ITT population (n=201). The GCSDD records the patient’s rating of the worst occurrence of each cardinal symptom of gastroparesis in the past 24 hours on a scale of 0 (no symptoms) to 5 (very severe). The study demonstrated that the difference between tradipitant and placebo in the primary endpoint was not significant (-1.55 versus -1.49, respectively; p=0.741). However, exploratory analysis revealed that an unbalanced use of rescue medications (e.g., ondansetron, prochlorperazine, promethazine) may have confounded the results. Among patients who did not use rescue medication, the average nausea severity was significantly improved for patients on tradipitant compared with placebo, overcoming the large placebo effect, at week 12 (-2.01 versus -1.32; p=0.0372). In addition, average nausea severity was significantly improved at week 12 for patients in the severity adjustment population, which excluded patients with zero or the highest severity of vomiting (p=0.0276) and significant effects were seen with adequate tradipitant exposure based on a pharmacokinetic analysis. The incidence and type of adverse events reported were similar between the treatment groups and included diarrhea, urinary tract infection, sinusitis, dizziness, and headache. Discontinuation due to adverse effects occurred in 6.9% of patients in the tradipitant group and 3% of patients in the placebo group.

In a double-blind, placebo-controlled, phase 2 trial (NCT02970968), tradipitant led to a significant decrease in GCSDD score at week 4 compared with placebo (-1.25 versus -0.73, respectively; p=0.0099) and a significant increase in the percentage of nausea-free days a week 4 (28.8% versus 15%, respectively; p=0.016) among 152 adults with idiopathic or diabetic GP.

Dosage and administration
In the clinical trials, tradipitant 85 mg was administered orally twice daily.

Place in therapy

GP is a chronic disorder of delayed gastric emptying without mechanical obstruction. Its characteristic symptoms of early satiety, nausea, vomiting, bloating, and abdominal pain have a significant effect on QOL, morbidity, and mortality. Definite diagnosis of GP (based on gastric emptying scintigraphy testing) was estimated at 21.5 per 100,000 persons in the U.S. in 2018; however, actual prevalence may be much higher since many patients remain undiagnosed. GP occurs mostly in women, with causes including diabetes, medications, surgery, or unknown.

Management of GP includes a diet that promotes gastric emptying (e.g., 4 to 5 small meals per day, decreased fat and fiber, increased liquid nutrition). Use of prokinetic medications, such as metoclopramide, cisapride (investigational limited access program) and erythromycin (4 weeks, off-label), to increase gastric emptying rate, and antiemetics for symptom control are suggested based on low quality of evidence. Notably, metoclopramide is FDA-approved for acute and recurrent diabetic GP, but its use is limited to a 3-month duration due to the risk of developing tardive dyskinesia.

NK-1R antagonists are proven to be effective in reducing nausea and vomiting in chemotherapy-induced emesis. If approved, tradipitant will be the first agent of this class to treat GP symptoms and the first new mechanism for GP to be approved in over 40 years; however, in clinical trials, it demonstrated mixed results in improving nausea in patients with GP. Tradipitant is also in phase 3 trials for motion sickness.

FDA approval timeline

September 18, 2024

Financial forecast (reported in millions)

The financial forecast for tradipitant is not currently available.

zanidatamab IV

Manufacturer: Jazz / Beigene

Proposed indications

Previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC)

Clinical overview

Mechanism of action
Zanidatamab is a HER2-targeted bispecific antibody that provides dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity.

Clinical trials
Zanidatamab monotherapy was evaluated in the open-label, single-arm, phase 2b HERIZON-BTC-01 trial (NCT05152147) in patients with unresectable, locally advanced, or metastatic HER2+ BTC. Enrolled patients were previously treated with gemcitabine-based therapy but were naïve to HER2-targeted therapy. Cohort 1 (n=80) included patients with in situ hybridization [ISH] positive and immunohistochemistry [IHC] 2+ or 3+ disease. Long-term follow-up data confirmed an ORR (primary endpoint) of 41.3%, with a complete response rate of 2.5%. Among patients with IHC 3+ (HER2+) tumors, the ORR was 51.6%, median DOR was 14.9 months, median PFS was 7.2 months, and median OS was 18.1 months. Among patients with IHC 2+ (borderline HER2 status) tumors, the ORR was 5.6%, median OS was 5.2 months, and median PFS was 1.7 months. In the single patient with IHC 2+ disease who responded to therapy, the DOR was 7.5 months. Zanidatamab was generally well tolerated, with a manageable safety profile. A serious increase in AST and ALT was experienced by one patient, which did not lead to treatment discontinuation.

Dosage and administration
In the HERIZON-BTC-01 trial, zanidatamab was administered IV as 20 mg/kg every 2 weeks.

Place in therapy

BTCs include gallbladder cancer and extrahepatic cholangiocarcinoma (CCA). In 2023, it was estimated that 12,220 new cases of BTC would be diagnosed in the U.S. and 4,510 deaths would occur due to the condition. BTCs are associated with a poor prognosis, as patients often have advanced disease upon diagnosis. Radiation therapy may be used in patients with unresectable disease. Systemic treatment for unresectable or metastatic BTC includes gemcitabine/cisplatin ± durvalumab (Imfinzi®; preferred) or pembrolizumab (Keytruda®). Subsequent therapy includes FOLFOX (folinic acid, fluorouracil, and oxaliplatin). HER2 overexpression or pathway activation is exhibited in about 5% to 20% of CCAs, and 15% to 30% of gallbladder cancer, for which off-label fam-trastuzumab deruxtecan-nxki (Enhertu®, for IHC 3+), trastuzumab/pertuzumab (Phesgo®) and trastuzumab + tucatinib (Herceptin® + Tukysa®) are recommended for HER2+ tumors after disease progression.

If approved, zanidatamab will be the first HER2-targeted treatment specifically indicated for patients with HER2+ locally advanced or metastatic biliary tract cancer. It demonstrated efficacy particularly in patients with IHC 3+ tumors. Zanidatamab is being evaluated in combination with first-line cisplatin and gemcitabine for the treatment of HER2+ BTC in a phase 2 trial (NCT03929666). Zanidatamab is also in phase 2 and phase 3 trials for HER2+ breast cancer and HER2+ gastric cancer, respectively.

FDA approval timeline

November 29, 2024

FDA Designations: Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review, seeking Accelerated Approval

Financial forecast (reported in millions)

Year	2024	2025	2026	2027	2028
Projected Yearly U.S. Sales	$0	$4	$11	$15	$22

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 Drug 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	July2024 Pipeline - Total US sales for 2028 (Dollars in millions)
botaretigene sparoparvovec	Ophthalmology / Gene therapy	$158
crinecerfont	Endocrine	$325
datopotamab deruxtecan	Oncology	$1,429
etripamil	Cardiovascular	$134
inavolisib	Oncology	$397
lebrikizumab	Immunology	$997
linvoseltamab	Oncology	$193
marstacimab	Hematology	$197
olezarsen	Cardiovascular	$254
palopegteriparatide	Endocrine	$694
RGX-121	Metabolic / Gene therapy	$71
sebetralstat	Immunology	$192
vanzacaftor/tezacaftor/deutivacaftor	Respiratory	$4,191
zenocutuzumab	Oncology	$82

Drug list

AThe 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
afamitresgene autoleucel	Adaptimmune	Synovial sarcoma	IV	BLA; Orphan Drug, Priority Review, RMAT	08/04/2024
remestemcel-L (Ryoncil^®)	Mesoblast	Acute GVHD (steroid-refractory)	IV	BLA; Fast Track, Orphan Drug	Sep 2024-Jan 2025
eladocagene exuparvovec (Upstaza^™)	PTC Therapeutics	Aromatic L-amino acid decarboxylase (AADC) deficiency	Intraputaminal	BLA; seeking Accelerated Approval, Orphan Drug, Priority Review, RPD	11/13/2024
obecabtagene autoleucel	Autolus	ALL (R/R, B-cell, adults)	IV	BLA; Orphan Drug, RMAT	11/16/2024
tabelecleucel	Pierre Fabre	Epstein-Barr virus-associated post-transplant lymphoproliferative disease	IV	BLA; Breakthrough Therapy, Orphan Drug, Priority Review	01/15/2025

None

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	Intratumoral	BLA; Fast Track	TBD
botaretigene sparoparvovec	Janssen	Retinitis pigmentosa	Subretinal	BLA; Fast Track, Orphan Drug	TBD
deramiocel	Nippon Shinyaku	DMD	IV	BLA; Orphan Drug, RMAT, RPD	TBD
dirloctocogene samoparvovec	Genentech	Hemophilia A	IV	BLA; Breakthrough Therapy, Orphan Drug	TBD
giroctocogene fitelparvovec	Pfizer	Hemophilia A	IV	BLA; Fast Track, Orphan Drug, RMAT	TBD
OCU400	Ocugen	Retinitis pigmentosa	Subretinal	BLA; Orphan Drug, RMAT	TBD
RGX-121	Regenxbio	Mucopolysaccharidosis II (Hunter syndrome)	Injection	BLA; seeking Accelerated Approval, Fast Track, Orphan Drug, RMAT, RPD	TBD
rilparencel	Prokidney	CKD	Injection	BLA; RMAT	TBD

None

Biosimilars

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
aflibercept (biosimilar to Regeneron's Eylea®)	Amgen	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	BLA	Jul-Sep 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	IV, SC	BLA	Oct-Nov 2024
denosumab (biosimilar to Amgen's Prolia®/Xgeva®)	Celltrion	Osteoporosis/osteopenia	SC	BLA	12/01/2024
trastuzumab (biosimilar to Genentech's Herceptin®)	Tanvex	Breast cancer (HER2+); Gastric cancer (HER2+)	IV	BLA	01/06/2025
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); COVID-19; CRS	IV, SC	BLA	01/28/2025
aflibercept (biosimilar to Regeneron's Eylea®)	Celltrion	DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD	Intravitreal	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

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 for interchangeability	SC	sBLA	09/06/2024
omalizumab (biosimilar to Genentech's Xolair^®)	Celltrion	Asthma; Chronic rhinosinusitis; Food allergies; Nasal polyposis; Urticaria for interchangeability	SC	sBLA	03/10/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
aflibercept (biosimilar to Regeneron's Eylea^®)	Novartis	DME; Wet AMD	Intravitreal	BLA	TBD
bevacizumab (biosimilar to Genentech’s Avastin^®)	Essex	DME; Wet AMD	Intravitreal	BLA	TBD

None

Specialty

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
narsoplimab	Omeros	Transplant-associated thrombotic microangiopathy	IV, SC	BLA; Breakthrough Therapy, Orphan Drug	Jul-Sep 2024
dasatinib (Dasynoc^®)	Xspray	CML	Oral	505(b)(2) NDA; Orphan Drug	07/31/2024
deuruxolitinib	Sun	Alopecia areata (moderate to severe)	Oral	NDA; Breakthrough Therapy, Fast Track	08/06/2024
midomafetamine	Lykos	PTSD	Oral	NDA; Breakthrough Therapy, Priority Review	08/11/2024
denileukin diftitox (Lymphir^™ )	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
palopegteriparatide	Ascendis	Hypoparathyroidism	SC	NDA; Orphan Drug	08/14/2024
seladelpar	Gilead	Primary biliary cholangitis (including pruritus, ursodeoxycholic acid inadequate response/intolerance)	Oral	NDA; Breakthrough Therapy, Orphan Drug, Priority Review	08/14/2024
vorasidenib	Les Laboratoires Servier	Glioma (diffuse, IDH-mutant)	Oral	NDA; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review	08/20/2024
linvoseltamab	Regeneron	Multiple myeloma (4th-line)	IV	BLA; Fast Track, Priority Review	08/22/2024
axatilimab	Syndax	Chronic GVHD (≥ 2 prior lines of systemic therapy, ages ≥ 6 years)	IV	BLA; Fast Track, Orphan Drug, Priority Review	08/28/2024
ocrelizumab/hyaluronidase (Ocrevus^® SC)	Genentech	MS	SC	BLA	09/13/2024
atezolizumab/hyaluronidase (Tecentriq^® SC)	Genentech	Alveolar soft part sarcoma; HCC; Melanoma; NSCLC; SCLC; Urothelial cancer	SC	BLA	09/15/2024
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 (prophylactic treatment)	SC	BLA; Fast Track, Orphan Drug	Oct-Dec 2024
marstacimab	Pfizer	Hemophilia A and B (without factor VIII or IX inhibitors)	SC	BLA; Fast Track, Orphan Drug	Oct-Dec 2024
paliperidone palmitate ER	Luye	Schizophrenia	IM	505(b)(2) NDA	10/09/2024
octreotide (Oclaiz^™)	Camurus	Acromegaly	SC	NDA	10/21/2024
treosulfan	Medexus	Allogeneic HSCT (preparation, in combination with fludarabine)	IV	NDA; Orphan Drug	10/30/2024
docetaxel	Zhuhai Beihai	Breast cancer; Gastric cancer; NSCLC; Prostate cancer	IV	505(b)(2) NDA	11/01/2024
zolbetuximab	Astellas	Gastric cancer (unresectable or metastatic, HER2-, CLDN18.2+, 1st-line)	IV	BLA; Orphan Drug	11/09/2024
inavolisib	Genentech	Breast cancer (HR+/HER2-, 1st-line, in combination with palbociclib & fulvestrant)	Oral	NDA; Breakthrough Therapy, Priority Review	11/27/2024
govorestat	Applied Therapeutics	Classic galactosemia	Oral	NDA; Fast Track, Orphan Drug, Priority Review, RPD	11/28/2024
acoramidis	Bridgebio/AstraZeneca	Transthyretin amyloid cardiomyopathy (ATTR-CM)	Oral	NDA; Orphan Drug	11/29/2024
zanidatamab	Jazz/Beigene	Biliary tract cancer (unresectable, locally advanced or metastatic, HER2+, previously-treated)	IV	BLA; seeking Accelerated Approval, Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review	11/29/2024
nemolizumab	Galderma	Atopic dermatitis (adults and adolescents, moderate to severe)	SC	BLA	12/14/2024
revakinagene taroretcel	Neurotech	Macular telangiectasia type 2	Implant	BLA; Fast Track, Orphan Drug, Priority Review	12/17/2024
irinotecan liposome	CSPC	Pancreatic cancer	IV	505(b)(2) NDA	12/18/2024
olezarsen	Akcea	Familial chylomicronemia syndrome	SC	NDA; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review	12/19/2024
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	12/20/2024
nivolumab/hyaluronidase (Opdivo^® SC)	Bristol-Myers Squibb	Bladder cancer; Melanoma; RCC; Solid tumors	SC	BLA	12/27/2024
ustekinumab (biosimilar to Janssen's Stelara^®)	Biocon/Janssen	PSO; PsA; CD; UC	IV, SC	BLA	12/27/2024
ensartinib	Xcovery	NSCLC (metastatic, ALK+)	Oral	NDA	12/28/2024
crinecerfont	Neurocrine	Congenital adrenal hyperplasia	Oral	NDA; Breakthrough Therapy, Orphan Drug, Priority Review	12/29/2024
cosibelimab	Checkpoint	Cutaneous squamous cell carcinoma (metastatic or locally advanced, ineligible for curative surgery or radiation)	IV	BLA	01/02/2025
vanzacaftor/tezacaftor/deutivacaftor	Vertex	CF (ages ≥ 6 years)	Oral	NDA; Orphan Drug, Priority Review	01/02/2025
zenocutuzumab	Merus	NSCLC (NRG1+); Pancreatic cancer (NRG1+)	IV	BLA; Breakthrough Therapy, Orphan Drug, Priority Review	01/06/2025
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
elamipretide	Stealth	Barth syndrome	SC	NDA; Fast Track, Orphan Drug, Priority Review, RPD	01/29/2025
fitusiran	Sanofi	Hemophilia A and B (with or without inhibitors)	SC	NDA; Fast Track, Orphan Drug	03/25/2025
condoliase	Ferring	Radicular leg pain associated with lumbar disc herniation	Intrathecal	BLA	05/14/2025
sebetralstat	Kalvista	HAE	Oral	NDA; Fast Track, Orphan Drug	06/18/2025
mirdametinib	Springworks	Neurofibromatosis type 1- associated plexiform neurofibromas (NF1-PN)	Oral	NDA; Fast Track, Orphan Drug, RPD	07/01/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
iptacopan (Fabhalta®)	Novartis	IgA nephropathy (Berger's disease)	Oral	sNDA; seeking Accelerated Approval, Priority Review	Jul-Nov 2024
benralizumab (Fasenra®)	AstraZeneca	Eosinophilic granulomatosis with polyangiitis	SC	sBLA; Orphan Drug	Jul-Dec 2024
fam-trastuzumab deruxtecan-nxki (Enhertu®)	Daiichi Sankyo/AstraZeneca	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
dostarlimab-gxly (Jemperli)	GlaxoSmithKline	Endometrial cancer (advanced or recurrent, in combination with carboplatin & paclitaxel)	IV	sBLA; Breakthrough Therapy, Priority Review	08/23/2024
sodium oxybate (Lumryz™)	Avadel	Narcolepsy (pediatrics)	Oral	sNDA; Orphan Drug	09/06/2024
dupilumab (Dupixent®)	Genentech	Nasal polyposis (add-on maintenance treatment for adolescents aged 12 to 17 years with inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP))	SC	sBLA	09/15/2024
amivantamab-vmjw (Rybrevant®)	Janssen	NSCLC (locally advanced or metastatic, EGFR exon 19 deletion or L858R substitution, disease progression on/after osimertinib)	IV	sBLA; Breakthrough Therapy	09/20/2024
pembrolizumab (Keytruda®)	Merck	Mesothelioma (pleural, unresectable or metastatic malignant, 1st-line, in combination with chemotherapy)	IV	sBLA; Priority Review	09/25/2024
dupilumab (Dupixent®)	Genentech	COPD	SC	sBLA; Breakthrough Therapy	09/27/2024
isatuximab-irfc (Sarclisa®)	Sanofi/Abbvie	Multiple myeloma (transplant ineligible, newly diagnosed, in combination with bortezomib, lenalidomide and dexamethasone [VRd])	IV	sBLA; Orphan Drug, Priority Review	09/27/2024
bimekizumab (Bimzelx®)	UCB	AS; nr-axSpA; PsA; HS	SC	sBLA	Oct-Dec 2024
osimertinib (Tagrisso®)	AstraZeneca	NSCLC (unresectable, stage III EGFR-mutated, after chemoradiotherapy)	Oral	sBLA; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review	Oct-Dec 2024
nivolumab (Opdivo®)	Bristol-Myers Squibb	NSCLC (resectable stage IIA to IIIB, neoadjuvant with chemotherapy, and adjuvant)	IV	sBLA; Breakthrough Therapy, Fast Track	10/08/2024
avacincaptad pegol (Izervay™)	Astellas	Dry AMD-related geographic atrophy	Intravitreal	sNDA; Breakthrough Therapy, Fast Track	11/19/2024
daratumumab/hyaluronidase-fihj (Darzalex Faspro® SC)	Janssen	Multiple myeloma (newly diagnosed, in combination with bortezomib, lenalidomide and dexamethasone for induction and consolidation, and with lenalidomide [VRd] for maintenance)	SC	sBLA	11/28/2024
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
guselkumab (Tremfya®)	Janssen/Novartis	UC (moderate to severe)	SC	sBLA	01/10/2025
lecanemab-irmb (Leqembi®)	Eisai	Alzheimer's disease (mild, monthly maintenance dosing)	IV	sBLA; Breakthrough Therapy, Fast Track	01/25/2025
mirikizumab-mrkz (Omvoh™)	Eli Lilly	CD	IV, SC	sBLA	01/31/2025
cobicistat/darunavir (Prezcobix®)	Janssen	HIV-1 infection (ages ≥ 6 years of age, weighing ≥ 25 kg)	Oral	sNDA	04/04/2025
guselkumab (Tremfya®)	Janssen/Novartis	CD (moderate to severe)	IV, SC	sBLA	04/18/2025
ranibizumab port delivery system (Susvimo®)	Genentech	DME; Diabetic retinopathy	Intravitreal implant	sBLA	May-Jun 2025
upadacitinib (Rinvoq®)	Abbvie	Giant cell arteritis	Oral	sNDA	7/11/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
abiraterone	Tavanta	Prostate cancer	Oral	NDA	TBD
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	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 (recurrent KRAS mutant, low-grade, serous, in combination with defactinib, ≥ 1 prior systemic therapy)	Oral	NDA; seeking Accelerated Approval, Breakthrough Therapy, Orphan Drug	TBD
bentracimab	Serb	Ticagrelor (Brilinta®) reversal	IV	BLA; Breakthrough Therapy	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
crovalimab	Genentech	Hemolytic uremic syndrome	IV, SC	BLA	TBD
CTX-009	Compass	Biliary tract cancer	IV	BLA; Fast Track	TBD
defactinib	Verastem	Ovarian cancer (KRAS mutant, low-grade, serous, ≥ 1 prior systemic therapy, in combination with avutometinib)	Oral	NDA; seeking Accelerated Approval, Breakthrough Therapy, 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
fazirsiran	Arrowhead	Alpha-1 antitrypsin deficiency	SC	NDA; Breakthrough Therapy, Fast Track, Orphan Drug	TBD
fenebrutinib	Genentech	MS	Oral	NDA	TBD
fianlimab	Regeneron	Melanoma	IV	BLA; Fast Track	TBD
garetosmab	Regeneron	Fibrodysplasia ossificans progressiva	IV	BLA; Fast Track, Orphan Drug	TBD
giredestrant	Genentech	Breast cancer (HR+/HER2-)	Oral	NDA; Fast Track	TBD
gold nanocrystal	Clene	ALS	Oral	NDA; Orphan Drug	TBD
hydroxypropyl beta cyclodextrin	Cyclo	Niemann-Pick disease type C	IV	NDA; Fast Track, Orphan Drug, RPD	TBD
ianalumab	Novartis	Autoimmne hepatitis; Sjogren's syndrome; ITP	SC	BLA; Fast Track	TBD
imlifidase	Sarepta	Kidney transplant rejection	IV	BLA; Fast Track, Orphan Drug	TBD
imsidolimab	Anaptysbio	Generalized pustular psoriasis	IV, SC	BLA; Orphan Drug	TBD
itepekimab	Regeneron	COPD	SC	BLA; Fast Track	TBD
JDQ-443	Novartis	NSCLC	Oral	NDA	TBD
ketamine	Hope	Bipolar disorder (suicidal); MDD (suicidal)	IV	505(b)(2) NDA; Fast Track	TBD
latozinemab	Alector	Frontotemporal dementia	IV	BLA; Breakthrough Therapy, Fast Track, Orphan Drug	TBD
lerodalcibep	LIB	Dyslipidemia/hypercholesterolemia; HeFH; 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-related pruritus	Oral	NDA; Orphan Drug	TBD
mepolizumab (Nucala®)	GlaxoSmithKline	COPD	SC	sBLA	TBD
molgramostim	Savara	Pulmonary alveolar proteinosis	Inhaled	BLA; Breakthrough Therapy, Fast Track, Orphan Drug	TBD
navepegritide	Ascendis	Achondroplasia	SC	NDA; Orphan Drug	TBD
nipocalimab	Janssen	Myasthenia gravis	IV	BLA; Fast Track, Orphan Drug	TBD
obicetrapib	New Amsterdam	Dyslipidemia/hypercholesterolemia	Oral	NDA	TBD
pabinafusp alfa	JCR	Mucopolysaccharidosis II (Hunter syndrome)	IV	BLA; Orphan Drug	TBD
paltusotine	Crinetics	Acromegaly	Oral	NDA; Orphan Drug	TBD
pegadricase	Swedish Orphan Biovitrum	Gout	IV	BLA	TBD
pegargiminase	Polaris	Mesothelioma	IM	BLA; Fast Track, Orphan Drug	TBD
pegzilarginase	Immedica	Arginase 1 deficiency	IV	BLA; Breakthrough Therapy, Fast Track, Orphan Drug, RPD	TBD
pelabresib	Novartis	Myelofibrosis	Oral	NDA; Fast Track, Orphan Drug	TBD
pelacarsen	Novartis	CVD (elevated lipoprotein[a])	SC	NDA; Fast Track	TBD
plozasiran	Arrowhead	Familial chylomicronemia syndrome	SC	NDA; Fast Track, Orphan Drug	TBD
QRX003	Quoin	Netherton syndrome	Topical	NDA	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
sefaxersen	Ionis/Roche	IgA nephropathy (Berger’s disease)	SC	NDA	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
sozinibercept	Opthea	Wet AMD	Intravitreal	BLA; Fast Track	TBD
sunvozertinib	Dizal (Jiangsu)	NSCLC	Oral	NDA; Breakthrough Therapy	TBD
tamibarotene	Syros	Myelodysplastic syndrome	Oral	NDA; Fast Track, Orphan Drug	TBD
telisotuzumab vedotin	Abbvie	NSCLC	IV	BLA; Breakthrough Therapy	TBD
tiragolumab	Genentech	Esophageal cancer; NSCLC	IV	BLA; Breakthrough Therapy, Orphan Drug	TBD
tolebrutinib	Sanofi	MS	Oral	NDA	TBD
vatiquinone	PTC	Friedreich's ataxia	Oral	NDA; Fast Track, Orphan Drug	TBD
venglustat	Sanofi	Fabry's disease; GM2 gangliosidosis (Tay-Sachs disease, Sandhoff disease)	Oral	NDA; Fast Track, Orphan Drug	TBD
vimseltinib	Ono	Pigmented villonodular synovitis	Oral	NDA; Fast Track	TBD
zanidatamab	Jazz	Gastric cancer	IV	BLA; Fast Track, Orphan Drug	TBD
zasocitinib	Takeda	PSO	Oral	NDA	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
alpelisib (Piqray^®)	Novartis	Breast cancer (HER2+)	Oral	sNDA	TBD
brolucizumab-dbll (Beovu^®)	Novartis	Diabetic retinopathy	Intravitreal	sBLA	TBD
cabozantinib (Cabometyx^®/Cometriq^®)	Exelixis	Prostate cancer	Oral	sNDA	TBD
canakinumab (Ilaris^®)	Novartis	NSCLC (adjuvant)	SC	sBLA	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); Breast cancer (TNBC)	IV	sBLA; Breakthrough Therapy	TBD
eplontersen (Wainua^™)	Ionis	Transthyretin amyloid cardiomyopathy	SC	sNDA; Fast Track, Orphan Drug	TBD
ganaxolone (Ztalmy^®)	Marinus	Tuberous sclerosis complex	IV, Oral	sNDA; Orphan Drug	TBD
inebilizumab-cdon (Uplizna^®)	Amgen	Autoimmune disorders (IgG4-related disease)	IV	sBLA	TBD
iptacopan (Fabhalta^®)	Novartis	C3 glomerulopathy (C3G); Hemolytic uremic syndrome	Oral	sNDA; Breakthrough Therapy, Orphan Drug, RPD	TBD
mitapivat (Pyrukynd^®)	Agios	SCD; Thalassemia	Oral	sNDA; Orphan Drug	TBD
mosunetuzumab-axgb (Lunsumio^™)	Genentech	DLBCL (2nd-line, in combination with polatuzumab vedotin)	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
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
sparsentan (Filspari^®)	Travere	Focal segmental glomerulosclerosis	Oral	sNDA; Orphan Drug	TBD
tislelizumab- jsgr (Tevimbra^®)	Beigene	HCC	IV	sBLA; Orphan Drug	TBD
venetoclax (Venclexta^®)	Abbvie/Genentech	Myelodysplastic syndrome	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
galantamine	Alpha Cognition	Alzheimer's disease (mild to 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/Eli Lilly	Gastroparesis	Oral	NDA	09/18/2024
xanomeline/trospium (KarXT)	Bristol-Myers Squibb	Schizophrenia	Oral	NDA	09/26/2024
epinephrine	ARS	Anaphylaxis	Intranasal	505(b)(2) NDA; Fast Track	10/02/2024
sulopenem etzadroxil/probenecid	Iterum	UTI (uncomplicated, adult women)	Oral	NDA; Fast Track, QIDP	10/25/2024
minocycline HCl 40 mg	Journey	Rosacea	Oral	505(b)(2) NDA	11/04/2024
vicagrel	Jiangsu Vcare	Thrombotic cardiovascular and cerebrovascular diseases	Oral	NDA	12/28/2024
chikungunya vaccine	Bavarian	Chikungunya virus immunization (ages ≥ 12 years)	IM	BLA; Breakthrough Therapy, Fast Track	Jan-Jun 2025
lamotrigine oral suspension	OWP	Bipolar disorder; Seizure disorder	Oral	505(b)(2) NDA	01/03/2025
diazoxide choline	Soleno	Prader-Willi syndrome (ages ≥ 4 years with hyperphagia)	Oral	505(b)(2) NDA; Breakthrough Therapy, Fast Track, Orphan Drug	Feb-Jun 2025
meningococcal vaccine (GSK3536819A)	GlaxoSmithKline	Meningococcal immunization	IM	BLA	02/14/2025
hydrocortisone oral solution (ET-400)	Eton	Adrenocortical insufficiency	Oral	NDA	02/28/2025
etripamil nasal spray	Milestone	Paroxysmal supraventricular tachycardia	Intranasal	NDA	03/28/2025
mRNA Coronavirus vaccine (Spikevax)	Moderna	COVID-19 immunization (SARS-CoV-2 variant JN.1)	IM	BLA; Fast Track	04/07/2025
chenodiol	Mirum	Cerebrotendinous xanthomatosis	Oral	NDA; Orphan Drug	06/28/2025

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
semaglutide (Wegovy^®)	Novo Nordisk	Chronic HFpEF	SC	sNDA; Priority Review	July 2024
tislelizumab-jsgr (Tevimbra^®)	Beigene	Esophageal squamous cell carcinoma (unresectable, recurrent, locally advanced, or metastatic, 1st-line)	IV	sBLA; Orphan Drug	July 2024
ACAM2000	Emergent	Mpox immunization	IM	sBLA	09/06/2024
vibegron (Gemtesa^®)	Sumitovant	Overactive bladder (in men receiving BPH pharmacotherapy)	Oral	sNDA	Oct-Dec 2024
dasiglucagon (Zegalogue^®)	Novo Nordisk	Congenital hyperinsulinism (CHI)	SC	sNDA; Orphan Drug, RPD	10/08/2024
anacaulase-bcdb (Nexobrid^®)	Vericel	Burn injury (pediatrics)	Topical	sBLA; Orphan Drug	11/08/2024
tirzepatide (Zepbound^®)	Eli Lilly	Sleep apnea with obesity	SC	sNDA; Fast Track	December 2024
tapinarof (Vtama^®)	Dermavant	Atopic dermatitis (ages ≥ 2 years)	Topical	sNDA	12/13/2024
sotagliflozin (Inpefa^®)	Lexicon	T1DM (with CKD)	Oral	sNDA	12/20/2024
semaglutide (Ozempic^®)	Novo Nordisk	Diabetic nephropathy	SC	sNDA	January 2025
smallpox and monkeypox vaccine (Jynneos^®) - freeze-dried formulation	Bavarian	Mpox immunization; Smallpox immunization	SC	sBLA	Jan-Mar 2025
brexpiprazole (Rexulti^®)	Otsuka	PTSD (in combination with sertraline)	Oral	sNDA	02/08/2025

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
azetukalner	Xenon	Partial/focal seizures	Oral	NDA	TBD
baclofen/naltrexone/sorbitol	Pharnext	Charcot-Marie-Tooth disease	Oral	NDA; Fast Track, Orphan Drug	TBD
bemnifosbuvir	Atea	COVID-19	Oral	NDA; Fast Track	TBD
blarcamesine	Anavex	Alzheimer’s disease	Oral	NDA	TBD
brensocatib	Insmed	Bronchiectasis	Oral	NDA; Breakthrough Therapy	TBD
brilaroxazine	Reviva	Schizophrenia	Oral	NDA	TBD
cadisegliatin	vTv	T1DM	Oral	NDA; Breakthrough Therapy	TBD
cagrilintide/semaglutide	Novo Nordisk	Obesity/overweight	SC	NDA	TBD
camlipixant	GlaxoSmithKline	Chronic cough	Oral	NDA	TBD
carbachol/brimonidine	Visus	Presbyopia	Ophthalmic	505(b)(2) NDA	TBD
COVID-19 vaccine (SP0253)	Sanofi	COVID-19	IM	BLA	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
gepotidacin	GlaxoSmithKline	UTI (uncomplicated); Urogenital gonorrhea	Oral	NDA; QIDP	TBD
navacaprant	Neumora	MDD	Oral	NDA	TBD
orforglipron	Eli Lilly	Obesity/overweight; T2DM	Oral	NDA	TBD
piclidenoson	Can-Fite	PSO	Oral	NDA	TBD
PL-9643	Palatin	DED	Ophthalmic	NDA	TBD
purified vero rabies vaccine (SP0087)	Sanofi	Rabies (post-exposure treatment)	IM	BLA	TBD
quadrivalent influenza mRNA vaccine (mRNA-1010)	Moderna	Seasonal influenza immunization	IM	BLA	TBD
ralinepag	United Therapeutics	PAH	Oral	NDA; Orphan Drug	TBD
relacorilant	Corcept	Cushing's syndrome	Oral	NDA; Orphan Drug	TBD
retatrutide	Eli Lilly	Obesity/overweight; T2DM	SC	NDA	TBD
RSV live attenuated vaccine	Sanofi	RSV immunization	Intranasal	BLA	TBD
survodutide	Boehringer Ingelheim	Obesity/overweight; T2DM	SC	NDA	TBD
suzetrigine	Vertex	Acute pain (moderate to severe)	Oral	NDA; Breakthrough Therapy, Fast Track	TBD
tebipenem pivoxil	GlaxoSmithKline	UTI (complicated)	Oral	NDA; Fast Track, QIDP	TBD
tiratricol	Rare Thyroid Therapeutics	Resistance to thyroid hormone type beta (RTH-b)	Oral	NDA; Fast Track, Orphan Drug, RPD	TBD
tradipitant	Vanda	Emesis	Oral	NDA	TBD
tramiprosate	Alzheon	Alzheimer's disease	Oral	NDA; Fast Track	TBD
ulixacaltamide	Praxis	Essential tremor	Oral	NDA	TBD
ulotaront	Sumitomo	Schizophrenia	Oral	NDA; Breakthrough Therapy	TBD
VHX-896	Vanda	Bipolar disorder; Schizophrenia	Oral	NDA	TBD
visomitin	Mitotech	DED	Ophthalmic	NDA	TBD
zoliflodacin	Innoviva	Gonorrhea (uncomplicated)	Oral	NDA; Fast Track, QIDP	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status	FDA Decision
dexmedetomidine (IgalmiT^™)	Bioxcel	Alzheimer’s disease-related neuropsychiatric symptoms	Oral	sNDA; Breakthrough Therapy	TBD
ibrexafungerp (Brexafemme^®)	GSK plc	Fungal infections (systemic, hospital indications)	Oral	sNDA; Fast Track, Orphan Drug, QIDP	TBD
lumateperone (Caplyta^®)	Intra-Cellular Therapies	MDD	Oral	sNDA	TBD
phentolamine 0.75% (Ryzumvi^™)	Viatris	Presbyopia	Ophthalmic	sNDA	TBD
roflumilast (Zoryve^®)	Arcutis	PSO	Topical	sNDA	TBD
semaglutide (Rybelsus^®)	Novo Nordisk	Obesity	Oral	sNDA	TBD

Name	Manufacturer	Clinical Use	Dosage Form	Development Status
camrelizumab	Jiangsu Hengrui	HCC (unresectable, 1st-line, in combination with rivoceranib)	IV	CRL
foscarbidopa/foslevodopa	Abbvie	Parkinson's disease	SC infusion	CRL
hepatitis B vaccine (recombinant), adjuvanted (Heplisav-B^®)	Dynavax	Hepatitis B prevention	IM	CRL
insulin icodec (Awiqli)	Novo Nordisk	T1DM; T2DM	SC	CRL
marnetegragene autotemcel (Kresladi™)	Rocket	Leukocyte adhesion deficiency-I	IV	CRL
naloxone (high-dose) (OX124)	Orexo	Opioid overdose	Intranasal	CRL
patritumab deruxtecan	Merck	NSCLC (locally advanced or metastatic, EGFR-mutated, ≥ 2 prior systemic therapies)	IV	CRL
prademagene zamikeracel	Abeona	Epidermolysis bullosa (recessive dystrophic)	Topical	CRL
ranibizumab (biosimilar to Genentech's Lucentis^®)	STADA Arzneimittel	Diabetic retinopathy; DME; Myopic choroidal neovascularization; Macular edema following RVO; Wet AMD	Intravitreal	CRL
rituximab (biosimilar to Genentech’s Rituxan^®)	Dr. Reddy's	CLL; Granulomatosis with polyangiitis/microscopic polyangiitis; NHL; Mature B cell NHL/mature B cell acute leukemia; Pemphigus vulgaris; RA	IV	CRL
rivoceranib	Elevar	HCC (unresectable, 1st-line, in combination with camrelizumab)	Oral	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

CLDN18.2+ Claudin-18.2-positive

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

HeFH Heterozygous Familial Hypercholesterolemia

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

HoFH Homozygous Familial Hypercholesterolemia

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

IgA Immunoglobulin A

IgG Immunoglobulin G

IgG1 Immunoglobulin G1

IgG4 Immunoglobulin G4

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

ISH In Situ Hybridization

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

KRAS Kirsten Rat Sarcoma viral oncogene homolog

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

mTOR mechanistic Target of Rapamycin

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

nr-axSpA Non-Radiographic Axial Spondyloarthritis

NRAS Neuroblastoma RAS Proto-Oncogene

NRG1+ Neuregulin-1-positive

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