As the year draws to a close, many individuals find themselves in a frantic race to complete their tasks before the holiday season, and the FDA was no exception. This period was marked by significant regulatory actions that highlight the agency’s ongoing commitment to public health and safety. Among these decisions, the approval of groundbreaking medications addresses pressing health issues, including the first-ever drug for a common chronic condition and an innovative regenerative medicine approach aimed at aiding trauma patients. As we reflect on this busy month, let’s explore some of the remarkable highlights from the FDA’s recent regulatory activities.
Trailblazing Approvals: Firsts in Medication
—For patients suffering from the widespread sleep disorder known as obstructive sleep apnea, treatment options have historically revolved around medical devices designed to assist with breathing. Now, with the FDA’s recent approval of Eli Lilly’s Zepbound, the landscape has changed, as it becomes the first drug specifically approved for this chronic condition. Clinical trials demonstrated that patients experienced significant improvements in their breathing, correlating with weight loss facilitated by Zepbound, which is particularly beneficial since obesity is a notable risk factor for sleep apnea. This approval not only underscores the efficacy of Zepbound but also positions it as a potential blockbuster in metabolic medicine, solidifying its role as one of Lilly’s leading products.
—Patients diagnosed with familial chylomicronemia syndrome, a rare inherited metabolic disorder, face a daunting challenge as their bodies are unable to effectively break down triglycerides, which are fats derived from food. To prevent severe complications, such as pancreatitis, these individuals must adhere to an extremely restrictive diet. The FDA’s approval of Ionis Pharmaceuticals’ olezarsen offers a pivotal therapeutic alternative. This once-monthly injectable genetic medicine functions by inhibiting the production of a liver protein that regulates triglyceride metabolism and will be marketed under the brand name Tryngolza. Significantly, this represents Ionis’s first product launch under its own banner after previously collaborating with larger firms.
—In cases where trauma necessitates the replacement of a blood vessel in the arm or leg, traditional methods typically involve grafting a vein from the patient or utilizing synthetic alternatives. However, a new option in regenerative medicine has emerged. The FDA has granted approval for Humacyte’s Symvess, a bioengineered blood vessel designed to restore blood flow and prevent limb loss when harvesting a vein is not viable. This innovative technology represents a significant advancement in the field of regenerative medicine, offering new hope for patients facing serious vascular injuries.
—The journey toward regulatory approval for Mesoblast’s remestemcel has been lengthy and complex. Previously rejected by the FDA in both 2020 and 2023, this allogeneic cell therapy is intended for treating graft versus host disease, a serious immune response triggered when donor T cells attack the recipient’s cells post-transplant. Now, the approval of remestemcel, branded as Ryoncil, comes as a major milestone, targeting acute graft versus host disease resistant to steroid treatment in patients aged two months and older. This decision marks the first successful regulatory approval for a cell therapy derived from mesenchymal stromal cells, showcasing the potential of advanced cellular therapies.
Significant Breakthroughs in Immunology
—Vtama, a product of Organon that was acquired from Roivant Sciences earlier this year, has received FDA approval as a topical treatment for atopic dermatitis in both adults and children aged two and older. Initially approved in 2022 for plaque psoriasis, this latest indication significantly expands its therapeutic reach, entering a much larger market segment characterized by numerous available treatments, including both branded and generic options.
—In another significant development within the realm of atopic dermatitis, Galderma secured FDA approval for nemolizumab, marketed as Nemluvio. This novel antibody treatment is designed to inhibit IL-31, a signaling protein implicated in the intense itching and inflammation associated with this chronic dermatological condition. The FDA has approved Nemluvio for use in patients aged 12 and older suffering from moderate-to-severe atopic dermatitis, marking its second regulatory approval this year, having first been authorized for treating prurigo nodularis.
Regulatory Advances for Rare Diseases
—Neurocrine Biosciences has received FDA approval for Crenessity, a medication targeting congenital adrenal hyperplasia, a rare inherited hormone disorder. This small molecule therapy effectively restores hormonal balance, with the FDA granting approval for both a pill formulation for adults and an oral solution for pediatric patients. Market analysts predict that Crenessity could achieve blockbuster sales, contingent upon securing regulatory approvals in other countries.
—While Novo Nordisk has established a strong reputation for its metabolic therapies, it has now strengthened its portfolio in rare diseases with the FDA’s approval of Alhemo, a drug designed to reduce bleeding episodes in patients with hemophilia A or B. Known during development as concizumab, Alhemo works by binding to TFPI, thereby preventing it from blocking factor Xa, a critical protein involved in the blood coagulation process. This mechanism mirrors that of Pfizer’s Hympavzi, which received FDA approval in October.
Both Alhemo and Hympavzi are administered via subcutaneous injections, offering alternative options to traditional intravenous hemophilia treatments. However, there is a key difference in dosing: Pfizer’s Hympavzi is a once-weekly injection, while Alhemo requires daily administration, which could impact patient adherence.
—Vertex Pharmaceuticals has expanded its cystic fibrosis (CF) treatment offerings with the FDA’s approval of Alyftrek, a combination therapy that incorporates three distinct compounds. Similar to Vertex’s existing CF treatments, Alyftrek acts as a modulator of the CFTR protein, which is essential for regulating the transport of chloride ions into and out of cells. The approval of Alyftrek was based on clinical evidence that compared its efficacy as a once-daily therapy to Trikafta, a previously approved Vertex medication that is taken twice daily. Notably, Alyftrek demonstrated comparable results to Trikafta in enhancing lung function while exhibiting superior performance in reducing sweat chloride levels, a crucial biomarker for CFTR function. Furthermore, Alyftrek addresses 31 additional CFTR mutations that existing modulators do not target, enhancing treatment options for patients. The FDA’s approval of Alyftrek came ahead of the anticipated regulatory decision date, further underscoring its potential impact.
Groundbreaking Developments in Cancer Therapeutics
—The FDA has granted accelerated approval to Merus Therapeutics for its drug zenacutuzumab, now branded as Bizengri, for the treatment of advanced non-small cell lung cancer and pancreatic adenocarcinoma. This approval is significant as it is the first for a medication targeting a specific genetic marker known as NRG1 gene fusion. Following the approval, Merus has entered into a licensing agreement with Partner Therapeutics for the U.S. commercialization of Bizengri.
—AstraZeneca’s blockbuster drug Imfinzi has expanded its FDA-approved indications to include limited-stage small cell lung cancer that has not advanced following platinum-based chemotherapy and radiation. Initially approved in 2017 for bladder cancer, Imfinzi received additional approval for extensive-stage lung cancer in 2020. The latest indication is backed by Phase 3 clinical trial results, demonstrating a 27% reduction in mortality risk compared to placebo, marking it as the first immunotherapy approved specifically for limited-stage small cell lung cancer.
—The FDA has approved Xcovery Holdings’ ensartinib, known as Ensacove, for adults diagnosed with advanced non-small cell lung cancer harboring ALK mutations. Patients prescribed this once-daily treatment must not have previously received an ALK inhibitor, ensuring it serves as a new option for those who have not explored this therapeutic pathway.
—Pfizer’s cancer treatment Braftovi has received accelerated approval for use as a first-line therapy in metastatic colorectal cancer associated with the BRAF V600E mutation. This approval allows Braftovi to be used in conjunction with Eli Lilly’s Erbitux and the chemotherapy regimen known as FOLFOX, both established therapies in colorectal cancer management. Initially approved in 2018 for advanced melanoma, Braftovi’s new indication further highlights Pfizer’s robust oncology portfolio, developed following the acquisition of Array Biopharma.
—Tevimbra, developed by BeiGene, has also gained FDA approval as a first-line treatment for gastric and gastroesophageal cancers when administered alongside chemotherapy. This marks the second regulatory approval for this checkpoint inhibitor, which was previously authorized for treating advanced or metastatic esophageal squamous cell carcinoma after prior chemotherapy. In an interesting turn, BeiGene is undergoing a rebranding process and will be known as BeOne Medicines starting January 2, with a new stock symbol of “ONC” on the Nasdaq.
Challenges Faced: Rejections and Warnings in Biotech
—Astellas Pharma faced a setback when the FDA rejected its proposal for less frequent eye injections of its drug Izervay. Approved for geographic atrophy treatment in 2023, Izervay is currently administered monthly to mitigate vision loss. Astellas sought to modify this to an every-other-month dosing schedule based on two-year Phase 3 trial data. However, the FDA raised concerns about proposed labeling language without citing safety or risk issues, hindering Izervay’s competitive edge against Apellis Pharmaceuticals’ Syfovre, which has both monthly and less frequent dosing options.
—In other news from Astellas, the FDA has added a black box warning to the label of Veozah, a menopause treatment, highlighting the risk of serious liver injury. This warning follows a safety communication issued after post-marketing reports indicated potential liver injury in a patient who used the medication for about 40 days. Veozah was initially approved in 2023 as a pioneering therapy for menopause.
—Applied Therapeutics is grappling with regulatory challenges, having received a double blow when the FDA rejected its application for govorestat, a treatment for the rare metabolic disorder galactosemia. The FDA cited “deficiencies in the clinical application” as the reason for the rejection. Shortly after, Applied also received a warning letter from the FDA, highlighting concerns about electronic data capture and a dosing error in the trial. The company has acknowledged these issues and plans to respond to the FDA.
—Intercept Pharmaceuticals has been facing mounting challenges with its drug Ocaliva, designed for primary biliary cholangitis (PBC), a rare liver disease. The FDA recently issued a safety alert regarding the risk of severe liver injury in patients without advanced liver cirrhosis, following the rejection of Intercept’s application for full approval of Ocaliva, which was initially granted accelerated approval in 2016. The situation worsened when the European Commission revoked Ocaliva’s conditional marketing authorization, with a ruling expected in 2025.
—The FDA has also denied Zealand Pharma’s application for glepaglutide, a treatment intended for short bowel syndrome, a rare condition where the small intestine is damaged or shortened, leading to nutrient absorption issues. The long-acting GLP-2 analog aimed to enhance nutrient absorption and decrease reliance on intravenous feeding. Zealand Pharma reported that the FDA requested additional evidence regarding the safety and efficacy of the application, and plans to pursue European approval in 2025.
—Lexicon Pharmaceuticals faced a disappointing outcome as the FDA rejected its request to expand the indication of its drug, sotagliflozin (brand name Zynquista), for adults with type 1 diabetes and chronic kidney disease. This decision followed a negative advisory committee vote in October, despite sotagliflozin’s previous approval for heart failure under the brand name Inpefa.
—Johnson & Johnson received a complete response letter regarding its injectable formulation of Rybrevant, a treatment for cancer associated with EGFR mutations. The intravenous version of Rybrevant was approved in 2021 for non-small cell lung cancer, but the FDA’s letter flagged manufacturing issues without expressing concerns about the new formulation’s safety or efficacy.
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