November 2024 FDA Approval Review

November 28, Product: Applied Therapeutics' Govorestat

Indication: Galactosemia

Three months after the initial target action date, the FDA declined to approve Applied Therapeutics' Govorestat for the treatment of the rare genetic metabolic disorder galactosemia. In its complete response letter (CRL), the regulatory agency cited "deficiencies" in the company's clinical application. In a report to investors on November 28, William Blair analysts wrote that Applied Therapeutics "suspected" the CRL was related to efficacy, not CMC or safety. Results from the Phase III ACTION-Galactosemia pediatric study, published in April 2023, showed that Govorestat did not meet its primary efficacy endpoint, which was a composite endpoint assessing four clinical measures in various domains of galactosemia symptoms. However, according to Applied Therapeutics, treatment with Govorestat resulted in a decrease in galactitol levels in the adult Phase I/II ACTION-Galactosemia study. The FDA initially set the target date for Govorestat as August 28 but delayed it in March, citing the need for more time to review the supplemental submission. Although the company was "disappointed" by the rejection, Applied Therapeutics CEO Soshana Shendelman stated in a release that they would "work with the FDA to address the concerns in the CRL and determine a pathway for rapid progression for Govorestat."

November 27, Product: Orphan Pharmaceuticals' Rapiblyk

Indication: Atrial Fibrillation in Intensive Care

AOP Orphan Pharmaceuticals received FDA approval for Rapiblyk for the treatment of atrial fibrillation in the intensive care setting. Rapiblyk is designed for intravenous administration and is an ultra-short-acting adrenergic receptor blocker known to affect heart rate. According to AOP, Rapiblyk has a "rapid onset," leading to a quick reduction in heart rate without significantly suppressing patients' blood pressure. The FDA's decision was supported by five randomized placebo-controlled trial results, which collectively showed a 40%-90% reduction in heart rate within 10 minutes of administration, compared to 0%-11% in the placebo group. Adverse events were more common in Rapiblyk-treated patients compared to the placebo group. Rapiblyk is intended for use in emergency and intensive care settings, as well as in surgical and intensive care environments, but is not indicated for the treatment of chronic arrhythmias.

November 25, Product: Shorla Oncology's Imkeldi

Indication: Various Types of Leukemia and Other Cancers

FDA approved Shorla Oncology's Imkeldi, an oral solution used to treat various types of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL), as well as other cancers such as myelodysplastic/myeloproliferative diseases, systemic mastocytosis, and cutaneous fibrosarcoma. The active ingredient in Imkeldi, imatinib, is a tyrosine kinase inhibitor that works by blocking the BCR-ABL protein, thereby preventing cancer cells from growing uncontrollably and triggering their death. Originally approved in 2001 by Novartis under the brand name Gleevec as tablets, Imkeldi's liquid formulation offers better dosage accuracy, according to CEO Sharon Cunningham, ensuring "more precise and consistent dosing." Cunningham also noted that Imkeldi provides "a convenient alternative for patients who have difficulty swallowing pills or require specific doses based on body surface area." According to Shorla, Imkeldi is the first FDA-approved oral liquid formulation of imatinib for certain leukemias.

November 22, Product: BridgeBio's Attruby

Indication: Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

For BridgeBio and patients with transthyretin amyloid cardiomyopathy (ATTR-CM), Thanksgiving arrived early, as the FDA approved the company's Attruby one week before the scheduled PDUFA date. Attruby's approval was supported by positive results from the Phase III ATTRibute-CM study, which showed that transthyretin stabilizers significantly reduced mortality and cardiovascular-related hospitalizations, while improving quality of life. According to BridgeBio's press release, Attruby is "the first and only approved product on label that states TTR is nearly completely stabilized." Analysts agree that the broad label (stating a reduction in hospitalization and death risks) will help it compete with Pfizer's Tafamidis and Alnylam's Amvuttra, whose supplemental new drug application was accepted by the FDA on Monday.

November 22, Product: Amneal Pharmaceuticals' Liraglutide

Indication: Type 2 Diabetes

FDA approved Amneal Pharmaceuticals' liraglutide, a generic version of the reference product, for improving blood sugar control in adults with type 2 diabetes, in combination with diet and exercise. Amneal's generic liraglutide will be available in 1.2 mL and 2.4 mL prefilled pens. Like the branded version Byetta (from AstraZeneca), the generic liraglutide carries similar side effects, including nausea, vomiting, dizziness, diarrhea, and hypoglycemia, along with other common side effects. Amneal's liraglutide is "one of the first generic GLP-1 injectable drugs approved in the U.S.," said Chief Business Officer Andy Boyer in a statement. According to a report from Coherent Marketing Insights, the GLP-1 market is expected to reach around $55.7 billion by 2031. The market is currently dominated by Eli Lilly and Novo Nordisk, which sell Tirzepatide and Semaglutide, respectively, effectively monopolizing the diabetes and obesity GLP-1 drug market. Outside the U.S., generic developers have begun to threaten the profits of these companies, especially in China and India.

November 21, Product: Jazz Pharmaceuticals and Zymeworks' Ziihera

Indication: HER2-Positive Biliary Tract Cancer

With the FDA approval of Ziihera, Jazz Pharmaceuticals and Zymeworks will compete against AstraZeneca and Daiichi Sankyo, whose antibody-drug conjugate Enhertu received broad approval in April 2024. Ziihera is a bispecific antibody that targets two distinct sites on the HER2 receptor. This unique binding profile provides Ziihera with several mechanisms of action, including dual blockade of HER2 signaling and removal of HER2 proteins from cancer cell surfaces. The bispecific antibody also enhances the immune system's anti-cancer activity. Phase IIb HERIZON-BTC-01 study data reported that patients treated with Ziihera had a confirmed objective response rate of 41.3%, with a median duration of treatment response of 12.9 months. Regarding safety, interim trial findings indicated good tolerability for Ziihera, with only two patients discontinuing treatment due to toxicity. Ziihera was approved under the FDA's accelerated pathway. To maintain its market position, Jazz and Zymeworks are conducting the Phase III HERIZON-BTC-302 confirmatory trial, evaluating Ziihera as first-line therapy in combination with chemotherapy, with or without PD-(L)1 inhibitors.

November 20, Product: UCB's Bimzelx

Indication: Moderate to Severe Hidradenitis Suppurativa

UCB received FDA approval for its subcutaneous Bimzelx (Bimekizumab-bkzx) for the treatment of adult patients with moderate to severe hidradenitis suppurativa. Bimzelx is a humanized IgG1 monoclonal antibody designed to target IL-17A and IL-17F cytokines, which play key roles in immune and inflammatory cascades. In October 2023, the FDA approved Bimzelx for adult patients with moderate to severe plaque psoriasis, and in September 2024, its label was expanded to include psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. The approval was supported by two Phase III studies—BE HEARD I and BE HEARD II. These trials showed that, compared to placebo, more patients treated with Bimzelx saw at least a 50% improvement in the signs and symptoms of hidradenitis suppurativa at 16 weeks. This treatment response was sustained at 48 weeks. Bimzelx also induced clinically meaningful improvements in several key secondary endpoints. According to UCB, Bimzelx is the first and only FDA-approved therapy to selectively block IL-17A and IL-17F.

November 20, Product: AstraZeneca's Izervay

Indication: Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)

FDA rejected AstraZeneca's request to include two-year data on its eye injection Izervay (Avacincaptad pegol intravitreal solution) label. Izervay is a polyethylene glycol-conjugated oligonucleotide that works by targeting and inhibiting the C5 protein, which is central to the formation of new blood vessels and inflammation seen in geographic atrophy (GA) caused by AMD. In the Phase II/III GATHER2 study, patients with GA were treated with Izervay at different doses, leading to a 27%-38% reduction in the growth of GA lesions. At the same time, Izervay also achieved a 21%-25% reduction in the annual rate of vision loss in patients with GA. AstraZeneca was hoping to expand the existing label with data on how Izervay can slow the progression of geographic atrophy, but the FDA noted that the data presented was not sufficient to support an updated label. This leaves the treatment's approval in a state of uncertainty for the time being.

November 19, Product: Soleno Therapeutics' DCCR

Indication: Prader-Willi Syndrome (PWS)

The FDA approved Soleno Therapeutics' DCCR (Diazoxide Choline Controlled-Release) for the treatment of Prader-Willi syndrome (PWS), a rare genetic disorder that causes insatiable hunger, developmental delays, and other symptoms. This approval follows the positive results from the Phase III ZEPHYR study, which demonstrated that DCCR significantly reduced hyperphagia (compulsive eating) and body fat mass in patients with PWS. DCCR is a controlled-release formulation of diazoxide, a drug that works by activating KATP channels, which help control appetite and energy balance. Soleno expects that DCCR will provide PWS patients with improved weight management, thus reducing the risk of obesity-related complications, including type 2 diabetes and cardiovascular disease. The approval marks the first FDA-approved treatment specifically for hyperphagia in PWS patients.

November 19, Product: Mylan's Promacta

Indication: Thrombocytopenia

Mylan received FDA approval for Promacta for the treatment of thrombocytopenia in adult and pediatric patients with chronic liver disease (CLD). Promacta is an oral thrombopoietin receptor agonist that stimulates platelet production. It is indicated for patients with chronic liver disease who are undergoing a medical procedure and have low platelet counts. The approval follows positive Phase III clinical trial results showing that Promacta increased platelet counts and reduced bleeding in patients with thrombocytopenia, making it an effective option for individuals with CLD who are at risk for complications related to low platelet levels. Promacta will be available for both adult and pediatric patients in tablet and powder forms.

November 17, Product: Amgen's Lumakras

Indication: KRAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

Amgen received approval for Lumakras, a targeted therapy designed for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC). Lumakras, a selective KRAS G12C inhibitor, works by inhibiting the mutant KRAS protein responsible for driving cancer cell proliferation. The approval was supported by results from the Phase II CodeBreaK100 study, which showed that Lumakras significantly improved progression-free survival in patients with advanced KRAS G12C-mutated NSCLC. The treatment also demonstrated a tolerability profile similar to other KRAS inhibitors, with common side effects including diarrhea, fatigue, and nausea. Lumakras is the first FDA-approved therapy targeting the KRAS G12C mutation in NSCLC.