Drug Approvals: October 2024 - Prime Therapeutics
Drug Approvals: October 2024
This monthly update of United States (U.S.) Food and Drug Administration (FDA) approvals provides a review of newly approved specialty drugs, new indications and recent first-time generic launches.
Specialty
New Drugs
Sept. 24, 2024 - levacetylleucine (Aqneursa)
IntraBio’s Aqneursa has received FDA approval for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighing ≥ 15 kg. This modified amino acid is the second treatment FDA-approved for NPC, a rare genetic condition leading to progressive neurological symptoms, organ dysfunction, and early death. Product will be supplied as 1 gram of levacetylleucine in a unit-dose packet for oral suspension. The recommended dosage is based on actual body weight (15 kg to < 25 kg; 25 kg to < 35 kg; ≥ 35 kg) and is given up to three times daily. Approval was based on a randomized, double-blind, placebo-controlled, two-period crossover study (n=60) in patients 5 to 67 years of age and demonstrated that Aqneursa led to better neurologic status (assessed by Scale for the Assessment and Rating of Ataxia score) compared to placebo (p<0.001) after 12 weeks of treatment. Aqneursa was reviewed under the Priority Review pathway and received Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA. Aqneursa is expected to compete with the oral capsule arimoclomol (Miplyffa). While Miplyffa is indicated in combination with miglustat for the treatment of neurological manifestations of NPC in adult and pediatric patients ≥ 2 years of age, Aqneursa is the only stand-alone therapy that is approved for treatment of NPC. Product is available with an average wholesale price (AWP) of $16,140 per 28 packets.
Oct. 10, 2024 - inavolisib (Itovebi)
The FDA has approved Genentech’s kinase inhibitor, Itovebi, indicated in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Patients should be selected for treatment of HR-positive, HER2-negative, locally advanced or metastatic breast cancer based on the presence of one or more PIK3CA mutations in plasma specimens. The FDA has also approved the FoundationOne Liquid CDx assay as a companion diagnostic device for identification of patients for treatment. Itovebi will be supplied as oral tablets in the strengths of 3 mg and 9 mg. Product is used in combination with palbociclib and fulvestrant and is dosed orally once daily until disease progression or unacceptable toxicity. Premenopausal and perimenopausal women should receive a luteinizing hormone-releasing hormone (LHRH) agonist, and in men, an LHRH agonist can be considered. A randomized, double-blind, placebo-controlled, multicenter study (INAVO120 [n=325]) demonstrated a statistically significant improvement in the major efficacy outcome assessing progression-free survival (PFS) in the study arm that included inavolisib in combination with palbociclib and fulvestrant compared to placebo in combination with palbociclib and fulvestrant (median PFS: 15 months versus 7.3 months, respectively; p<0.0001). Itovebi is expected to compete with similar agents such as alpelisib (Piqray) and capivasertib (Truqap), which are recommended in the National Comprehensive Cancer Network (NCCN) guidelines as targeted therapies for patients with recurrent unresectable or metastatic invasive breast cancer that is HR-positive, HER2-negative with a PIK3CA activating mutation. Itovebi was granted Priority Review, received Breakthrough Therapy designation and utilized Project Orbis for the FDA’s review. Launch of the product is expected within weeks of approval with pricing to follow.
Oct. 11, 2024 - marstacimab-hncq (Hympavzi)
Pfizer has received FDA approval for the tissue factor pathway inhibitor (TFPI) antagonist Hympavzi for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ≥ 12 years of age with: (1) hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors, or (2) hemophilia B (congenital factor IX deficiency) without factor IX inhibitors. Approval marks the first and only anti-TFPI approved in the U.S. for the treatment of hemophilia A or B. Hympavzi will be supplied as 150 mg/mL single-dose prefilled syringes or pens. It is also the first hemophilia therapy approved for administration with a prefilled auto-injector pen. The recommended dosage is administered as a subcutaneous (SC) injection with a loading dose followed by maintenance dosing given one week after the loading dose and weekly thereafter on the same day each week, at any time of day. If patients experience breakthrough bleeds, factor VIII and factor IX products can be administered for management; additional doses of Hympavzi should not be used for breakthrough bleeding. Approval was based on an open-label, multicenter, phase 3 study (BASIS) conducted in 116 adult and pediatric male patients that demonstrated a significant reduction in annualized bleeding rate (ABR) for treated bleeds by 92% (p<0.0001) after a 12-month active treatment period with Hympavzi compared to on-demand treatment with factor-based therapy during a six month observational period; Hympavzi also demonstrated non-inferiority to factor-based routine prophylaxis during a six month observational phase. Other products indicated for routine prophylaxis of bleeding episodes in patients with hemophilia A or B include the factor VIII and factor IV products as well as other hemophilia products (e.g., emicizumab-kxwh [Hemlibra]). Hympavzi was granted Orphan Drug designation for this use. Product availability is to be determined (TBD) with pricing to follow.
New Formulations
Sept. 27, 2024 - octreotide acetate (Bynfezia Pen)
505(b)(2) NDA approval; Standard Review; Sun previously discontinued this product in 2021
Somatostatin analogue
Indicated for (1) reduction in blood levels of growth hormone and insulin growth factor 1 (IGF-1) in acromegaly patients who have had an inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses, (2) symptomatic treatment of patients with metastatic carcinoid tumors where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease, and (3) treatment of profuse watery diarrhea associated with vasoactive intestinal peptide (VIP)-secreting tumors
Bynfezia has a limitation of use which states that improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with octreotide injection, since trials were not optimally designed to detect such effects
Solution for injection: 7,000 mcg/2.8 mL (2,500 mcg/mL) octreotide (as acetate) in a 2.8 mL single-patient-use prefilled pen
SC injection given between two and four times per day; patients or caregiver can administer following proper training
Product will be available from Sun with launch timeframe TBD and pricing to follow
Oct. 16, 2024 - foscarbidopa and foslevodopa (Vyalev)
505(b)(2) NDA approval; Standard Review; Orphan Drug designation; prodrug formulation converted in vivo to carbidopa and levodopa
Combination of foscarbidopa (an aromatic amino acid decarboxylation inhibitor) and foslevodopa (an aromatic amino acid)
Indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease
Solution for injection: 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL single-dose vial
SC infusion, preferably in the abdomen, with the Vyafuser pump; patients or caregivers who are selected for treatment should be able to understand and use the delivery system and require proper training prior to starting therapy; the continuous infusion rate is based on the total levodopa dosage and can be administered over the patient’s waking hours or for 24 hours; details on extra dosing and an optional loading dose are detailed in the prescribing information
Product is available from Abbvie with an AWP of $393.02 per 10 mL single-dose vial
New Biosimilars
Sept. 27, 2024 - ustekinumab-aauz (Otulfi)
Fresenius Kabi has received FDA approval for Otulfi as a biosimilar to ustekinumab (Stelara). This human interleukin (IL)-12 and IL-23 antagonist is indicated for all of the indications of reference product Stelara: adults with (1) moderate to severe plaque psoriasis (PsO) who are candidates for phototherapy or systemic therapy; (2) active psoriatic arthritis (PsA); (3) moderately to severely active Crohn’s disease; or (4) moderately to severely active ulcerative colitis, and pediatric patients ≥ 6 years of age with (1) moderate to severe PsO, who are candidates for phototherapy or systemic therapy; or (2) active PsA. Otulfi is approved as a 45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe for SC administration and a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial for intravenous (IV) infusion. In addition to these presentations, reference drug Stelara is also approved as a 45 mg/0.5 mL solution in a single-dose vial. Otulfi is the fourth Stelara biosimilar to receive FDA-approval. Other FDA-approved biosimilars to Stelara include: ustekinumab-aekn (Selarsdi), ustekinumab-ttwe (Pyzchiva) and ustekinumab-auub (Wezlana), the latter of which has received interchangeability designation. None of the Stelara biosimilars have launched due to terms of settlement and licensing agreements; however, launch is anticipated in 2025. Otulfi is expected to launch no later than Feb. 22, 2025, with pricing to follow.
Oct. 10, 2024 - ustekinumab-srlf (Imuldosa)
The FDA has approved Accord BioPharma’s Imuldosa as biosimilar to ustekinumab (Stelara). This human IL-12 and IL-23 antagonist is indicated for all of the indications of reference product Stelara: adults with (1) moderate to severe PsO who are candidates for phototherapy or systemic therapy; (2) active PsA; (3) moderately to severely active Crohn’s disease; or (4) moderately to severely active ulcerative colitis, and pediatric patients ≥ 6 years of age with (1) moderate to severe PsO, who are candidates for phototherapy or systemic therapy; or (2) active PsA. Imuldosa is approved as a 45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe for SC administration and a 130 mg/26 mL (5 mg/mL) solution in a single-dose vial for IV infusion. In addition to these presentations, reference drug Stelara is also approved as a 45 mg/0.5 mL solution in a single-dose vial. Imuldosa is the fifth Stelara biosimilar to receive FDA approval. Product availability is expected in the first half of 2025 with pricing to follow.
New or Expanded Indications
Sept. 20, 2024 – bimekizumab-bkzx (Bimzelx)
UCB; humanized IL-17A and F antagonist administered SC
New indications: (1) adults with active PsA, (2) adults with active ankylosing spondylitis (AS), and (3) adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation
Administered as a SC injection every four weeks; if the patient has coexisting moderate to severe PsO, the dosage and administration for the PsO indication should be used; patients can self-inject after training in injection technique
Other indication: select adults with moderate to severe PsO
Sept. 20, 2024 - isatuximab-irfc (Sarclisa)
Sanofi-Aventis; CD38-directed cytolytic antibody administered IV; Priority Review and Orphan Drug designation for this new indication
New indication: in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT)
Administered as a weight-based dose based on actual body weight and given as an IV infusion on days 1, 8, 15, 22, and 29 during cycle one; days 1, 15, and 29 (every two weeks) for cycles two through four; days 1 and 15 (every two weeks) for cycles five through 17; and day 1 (every four weeks) for cycles 18 and beyond (28-day cycles); treatment is continued until disease progression or unacceptable toxicity
Other indications: select adults with multiple myeloma, in combination with other agents
Sept. 25, 2024 - osimertinib (Tagrisso)
AstraZeneca; kinase inhibitor supplied as oral tablets; Breakthrough Designation and Priority Review for this new indication
New indication: for the treatment of adult patients with locally advanced, unresectable (stage III) non-small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
Administered following platinum-based chemoradiation therapy orally once daily, with or without food, until disease progression or unacceptable toxicity
Other indications: select patients with NSCLC either as monotherapy or in combination with other agents
Sept. 27, 2024 - dupilumab (Dupixent)
Regeneron; IL-4 receptor alpha antagonist administered SC; Priority Review for this new indication
New indication: add-on maintenance treatment of adult patients with inadequately controlled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype; Dupixent is not indicated for relief of acute bronchospasm
Administered as a SC injection every other week; the prefilled syringe or prefilled pen can be administered by a caregiver or patient
Other indications: select patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nodularis
Oct. 3, 2024 - nivolumab (Opdivo)
Bristol-Myers Squibb; programmed death receptor-1 (PD-1)-blocking antibody administered IV; review conducted under Project Orbis
New indication: in combination with platinum-doublet chemotherapy for the neoadjuvant treatment of adults with resectable (tumors ≥ 4 cm or node positive) NSCLC and no known EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent Opdivo as adjuvant treatment after surgery
Administered as an IV infusion with platinum-doublet chemotherapy on the same day every three weeks for up to four cycles or until disease progression or unacceptable toxicity, then continued as single-agent Opdivo every four weeks after surgery for up to 13 cycles (approximately one year) or until disease recurrence or unacceptable toxicity
Other indications: many different cancers
Oct. 16, 2024 - sodium oxybate (Lumryz)
Avadel CNS Pharmaceuticals; central nervous system (CNS) depressant supplied as an extended-release (ER) oral suspension supplied in packets of powder; schedule III-controlled substance; Orphan Drug designation for expanded patient population of pediatric narcolepsy
Expanded indication: pediatric patients ≥ 7 years of age with narcolepsy for the treatment of cataplexy or excessive daytime sleepiness; previously, this indication was only approved for adults
Administered as an ER oral suspension taken as a single dose at bedtime with dosing based on body weight (weighing ≥ 45 kg); dosage should be titrated up at weekly intervals; for pediatric patients weighing < 45 kg, the recommended starting dosage cannot be achieved with available strengths of Lumryz; therefore, an alternative sodium oxybate product should be used to initiate treatment; maximum recommended dosage for pediatric patients is based on body weight (20 kg to < 30 kg, 30 kg to < 45 kg); there is insufficient dosing information for pediatric patients who weigh < 20 kg
Traditional
New Drugs
Sept. 26, 2024 - xanomeline and trospium chloride (Cobenfy)
The FDA has approved Bristol-Myers Squibb’s Cobenfy for the treatment of schizophrenia in adults. Cobenfy is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist. This is the first antipsychotic drug approved to treat schizophrenia that targets cholinergic receptors which is a new mechanism of action for the treatment of this condition. Cobenfy will be supplied as oral capsules (xanomeline/trospium chloride) in the following strengths: 50 mg/20 mg, 100 mg/20 mg and 125 mg/30 mg. The recommended dosage is started at the lowest capsule strength taken twice daily for at least two days, then increased to the next capsule strength taken twice daily for at least five days. Depending on patient tolerability and response, the dosage may be further increased to the highest capsule strength twice daily. A slower titration should be considered for geriatric patients; the maximum recommended dosage is also lower for these patients. Capsules are taken at least one hour prior to a meal or a minimum of two hours following a meal. Approval was based on data from two identically designed, randomized, double-blind, placebo-controlled, phase 3 trials (EMERGENT-2; n=252 and EMERGENT-3; n=256) that demonstrated a significantly greater reduction in schizophrenia symptoms from baseline (assessed by the Positive and Negative Syndrome Scale total score) compared to placebo (p<0.0001 for both studies) at week five. The new agent is expected to compete with existing antipsychotic medications that antagonize the dopamine receptors (e.g., risperidone, olanzapine, others). Cobenfy is commercially available and carries an AWP of $2,220 per 60 capsules.
New Formulations
None
New or Expanded Indications
Oct. 15, 2024 - dalteparin sodium (Fragmin)
Pfizer; low molecular weight heparin administered SC
Expanded indication: pediatric patients from birth (gestational age ≥ 35 weeks) to < 1 month of age for the treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence; previously, this indication was approved for pediatric patients ≥ 1 month of age (not indicated for the acute treatment of VTE)
Administered as a SC weight-based starting dose dependent on patient age (e.g., birth to < 2 years of age; 2 years of age to < 8 years of age; 8 years to < 17 years); all doses given twice daily with dose adjustments to achieve target anti-Xa levels; the maintenance dose should be individualized based on the dose that achieves target anti-Xa level collected 4 hours after administration; benzyl alcohol-free formulations (prefilled syringes) should be used whenever possible in pediatric patients; for treatment of neonates, use the 10,000 units/4 mL (2,500 units/mL) single-dose vials, as this presentation is also preservative-free
First Generic Drug Launches
hydrocortisone sodium succinate for injection (Solu-Cortef): Cipla launched a generic to Pfizer’s Solu-Cortef (100 mg). This glucocorticoid is indicated when oral therapy is not feasible for various allergic states, dermatologic diseases, endocrine disorders, gastrointestinal diseases, hematologic disorders, trichinosis, tuberculous meningitis, neoplastic diseases, nervous system edema, ophthalmic diseases, renal diseases, respiratory diseases and rheumatic disorders. Dosage is dependent on indication for use. In 2023, Solu-Cortef generated $101 million in annual sales in the U.S.
octreotide acetate for injectable suspension (Sandostatin LAR Depot): Teva launched a generic to Novartis’ Sandostatin LAR Depot intramuscular (IM) injection kit (20 mg and 30 mg). This somatostatin analogue is indicated for patients who have responded to and tolerated octreotide acetate SC injection for (1) acromegaly; (2) severe diarrhea/flushing episodes associated with metastatic carcinoid tumors; or (3) profuse watery diarrhea associated with VIP-secreting tumors. It is administered SC every four weeks by a trained health care professional into the gluteal muscle. Sandostatin LAR Depot generated $1,511 million in annual U.S. sales in 2023.
paclitaxel protein-bound particles for injectable suspension (Abraxane): Sandoz launched the first true generic to Bristol-Myers Squibb’s Abraxane IV suspension (100 mg). The product is a microtubule inhibitor indicated for select cancers (e.g., certain patients with breast cancer, NSCLC, adenocarcinoma of the pancreas) and is administered as an IV infusion with frequency dependent on indication. Abraxane generated $1,090 million in sales in 2023.
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