Product approvals in regenerative medicine and rare diseases are among the highlights in our recap of recent FDA regulatory decisions.
\nThe post FDA Wraps Up 2024 Handing Out Several Notable Regulatory Decisions appeared first on Above the Law.<\/p>\n
For many people, the end of the year is a mad rush to wrap things up before the holidays, and so it was for the FDA.<\/p>\n
Notable regulatory decisions include the first drug approval for a prevalent chronic condition and a novel regenerative medicine approach to help trauma patients. In one case, a new drug approval comes as its developer takes on a new identity in the new year.<\/p>\n
Here\u2019s a look back at some highlights from a busy regulatory month:<\/p>\n
Notable Firsts<\/strong><\/p>\n \u2014The prevalent sleeping disorder obstructive sleep apnea has historically been managed with a medical device that helps breathing. Eli Lilly\u2019s Zepbound is now the first FDA-approved drug treatment for the chronic condition<\/a>.<\/strong> Obesity is a risk factor for sleep apnea and clinical trial results showed that weight reductions from treatment with Zepbound were accompanied by breathing improvement. Approval in obstructive sleep apnea adds another potential blockbuster indication for a metabolic medication that has fast become one of Lilly\u2019s top-selling products.<\/p>\n \u2014Patients who have the rare inherited metabolic disorder familial chylomicronemia syndrome lack the ability to break down triglycerides, a type of fat from food.<\/strong> The only way to avoid potentially fatal complications to the pancreas is by maintaining an extremely restrictive diet. Approval of Ionis Pharmaceuticals\u2019 olezarsen<\/a> gives patients a therapeutic option. The once-monthly injected genetic medicine, which is designed to block the body\u2019s production of a liver protein that regulates triglyceride metabolism, will be marketed under the brand name Tryngolza. Ionis previously brought drugs through late-stage development and commercialization under partnerships with larger companies. Tryngolza will be the first product Ionis commercializes on its own<\/a>.<\/p>\n \u2014When trauma to an arm or leg requires replacement of a blood vessel, the standard treatment is grafting a vein from the patient or implanting a synthetic vein. Now there\u2019s a new regenerative medicine option.<\/strong> Humacyte won FDA approval for Symvess<\/a>, a bioengineered blood vessel for restoring blood flow to avoid the loss of a limb when grafting a vein from the patient is not feasible. Here\u2019s more about the biotech\u2019s regenerative technology<\/a>.<\/p>\n \u2014Mesoblast\u2019s regulatory approval was a long time coming. In 2020 and 2023, the FDA turned down the Australian company\u2019s application for remestemcel, an allogeneic cell therapy for graft versus host disease, an immune response<\/strong> that develops when donor T cells attack the recipient\u2019s cells following a transplant procedure. Remestemcel, brand name Ryoncil, is made from mesenchymal stromal cells sourced from the bone marrow of healthy donors. The product\u2019s approval<\/a> covers acute graft versus host disease that is refractory to treatment with steroids in patients age 2 months and older. It\u2019s the first affirmative regulatory decision for a cell therapy made from mesenchymal stromal cells.<\/p>\n Approvals in Immunology<\/strong><\/p>\n \u2014Vtama, an Organon drug acquired from Roivant Sciences earlier this year<\/a>, received FDA approval as a treatment for atopic dermatitis<\/a> in adults and children age 2 and older.<\/strong> The drug is topical cream that was initially approved in 2022 as a treatment for plaque psoriasis<\/a>. Approval in atopic dermatitis brings the product to a much larger dermatologic indication, albeit one served by many branded and generic medications.<\/p>\n \u2014In other atopic dermatitis news, Galderma landed FDA approval for nemolizumab<\/a>, brand name Nemluvio.<\/strong> The drug is an antibody designed to block IL-31, a signaling protein associated with the itch and inflammation of the chronic skin disorder. FDA approval of Nemluvio covers use of the drug in patients age 12 and older who have moderate-to-severe atopic dermatitis. It\u2019s the second approval in the past year for Nemluvio, which was first approved over the summer as a treatment for prurigo nodularis.<\/p>\n Rare Disease Regulatory Decisions<\/strong><\/p>\n \u2014Neurocrine Biosciences received approval for Crenessity<\/a>, a treatment for the rare inherited hormone disorder congenital adrenal hyperplasia.<\/strong> The small molecule helps bring the hormone imbalance back to more normal levels. The FDA approved a pill formulation for adults and an oral solution for pediatric patients. Analysts project Crenessity could achieve blockbuster sales, pending regulatory approvals in other countries.<\/p>\n \u2014Novo Nordisk is best known for metabolic medicines, but its rare disease portfolio is getting a boost with FDA approval of Alhemo<\/a>, a drug that reduces bleeding episodes in patients with either hemophilia A or B.<\/strong> Alhemo, known in development as concizumab, is an antibody designed to bind to TFPI, preventing that protein from blocking factor Xa, a different protein that plays a role in blood clotting. That\u2019s the same mechanism of action as Pfizer\u2019s Hympavzi, which won its FDA approval in October<\/a>.<\/p>\n Both drugs are subcutaneous injections that provide alternatives to intravenously infused hemophilia therapies. But Pfizer\u2019s once-weekly Hmypavzi has a dosing edge over Alhemo, which must be injected once daily.<\/p>\n \u2014Vertex Pharmaceuticals is adding a new cystic fibrosis (CF) drug to its portfolio with FDA approval of Alyftrek<\/a>, which combines three compounds in a single therapy.<\/strong> Like Vertex\u2019s other CF therapies, Alyftrek is a modulator of the CFTR a protein that regulates the movement of chloride ions into and out of cells.<\/p>\n Alyftrek\u2019s approval is based on clinical data comparing the once-daily therapy to Trikafta, a Vertex triple combination drug initially approved in 2019 as a twice-daily CF treatment. Results showed Alyftrek was non-inferior to Trikafta on a key measure of lung function and was superior in reducing sweat chloride levels, which is a surrogate indicator of the function of CFTR proteins. Besides the dosing advantage, Alyftrek addresses 31 additional mutations that are not addressable by other CFTR modulators. The Dec. 20 approval of Alyftrek came nearly two weeks ahead of the Jan. 2 target date for a regulatory decision.<\/p>\n Developments in Cancer Drugs<\/strong><\/p>\n \u2014The FDA awarded accelerated approval<\/a> to Merus Therapeutics drug zenacutuzumab as a treatment for advanced cases of two types of cancer: non-small cell lung cancer and pancreatic adenocarcinoma.<\/strong> It\u2019s the first approval for a drug that addresses a genetic signature called an NRG1 gene fusion. Netherlands-based Merus will market the bispecific antibody under the brand name Bizengri. In a deal struck days prior to the approval announcement, Partner Therapeutics licensed<\/a> U.S. commercialization rights to Bizengri.<\/p>\n \u2014The blockbuster AstraZeneca drug Imfinzi expanded its FDA-approved uses<\/a> to include limited-stage small cell lung cancer that has not progressed following concurrent platinum-based chemotherapy and radiation therapy.<\/strong> The checkpoint inhibitor was first approved in 2017 for bladder cancer and added extensive-stage lung cancer as a new indication in 2020. The drug\u2019s latest approval is based on Phase 3 results showing a 27% reduction in the risk of death compared to a placebo. AstraZeneca said<\/a> the FDA decision makes Imfinzi the first immunotherapy approved for limited-stage small cell lung cancer.<\/p>\n \u2014Xcovery Holdings drug ensartinib, brand name Ensacove, was approved<\/a> to treat adults with advanced cases of non-small cell lung cancer that is positive for ALK mutations.<\/strong> Patients prescribed the once-daily pill must not have previously received an ALK inhibitor.<\/p>\n \u2014Pfizer cancer drug Braftovi landed accelerated approval<\/a> as a first-line treatment for metastatic colorectal cancer driven by the BRAF V600E mutation.<\/strong> The approval covers use of the drug in combination with Eli Lilly\u2019s Erbitux and the chemotherapy regimen referred to as FOLFOX, both standard colorectal cancer therapies. Braftovi, a small molecule inhibitor of BRAF V600E, was initially approved in 2018<\/a> for advanced cases of melanoma. The drug came from Pfizer\u2019s 2019 acquisition<\/a> of Array Biopharma.<\/p>\n \u2014Tevimbra, a cancer immunotherapy developed by BeiGene, received FDA approval<\/a> as a first-line treatment for gastric and gastroesophageal junction cancers when used in combination with chemotherapy.<\/strong> It\u2019s the second FDA approval for the checkpoint inhibitor, which was approved last March<\/a> for treating advanced or metastatic esophageal squamous cell carcinoma after prior treatment with chemotherapy.<\/p>\n The new year means a new identity for BeiGene<\/a>. The cancer drug developer is changing its name to BeOne Medicines. Starting Jan. 2, the company\u2019s stock symbol on the Nasdaq will be \u201cONC.\u201d<\/p>\n Rejections, Warnings & More Bad News in Biotech<\/strong><\/p>\n \u2014Astellas Pharma\u2019s bid to bring patients less-frequent eye injections of its drug Izervay was rejected<\/a> by the FDA.<\/strong> Izervay, approved for treating geographic atrophy in 2023<\/a>, is administered monthly to slow progression of the vision-loss disorder. Astellas sought approval for every-other-month dosing based on two-year Phase 3 data. According to Astellas, no safety benefit\/risk issues were cited but the FDA took issue with a statistical matter related to labeling language proposed by the company. The rejection will limit Izervay\u2019s ability to compete against Apellis Pharmaceuticals\u2019 geographic atrophy drug Syfovre, which is approved for both monthly and every-other-month dosing<\/a>.<\/p>\n \u2014In other Astellas news, the label for menopause drug Veozah now sports a black box warning<\/a> for the risk of serious liver injury.<\/strong> The warning follows a FDA safety communication issued in September after a postmarketing report of a patient who developed signs and symptoms of liver injury after taking the once-daily pill for about 40 days. Veozah won FDA approval in 2023 as the first in a new class of therapies for menopause<\/a>.<\/p>\n \u2014Applied Therapeutics received a double dose of bad regulatory news. First the FDA rejected the biotech\u2019s application for govorestat<\/a>, a drug developed as a treatment for the rare metabolic disease galactosemia.<\/strong> According to Applied, the agency cited \u201cdeficiencies in the clinical application.\u201d<\/p>\n Days after the FDA complete response letter, the FDA sent Applied a warning letter.<\/a> The trial and the drug are redacted in the public version of the letter, but in a regulatory filing<\/a>, Applied acknowledged the FDA\u2019s concerns are about the govorestat galactosemia trial. Applied said the warning letter identified issues with electronic data capture and a dosing error in the dose-escalation portion of the study \u2014 both of which the company believed it had already addressed with the agency. Applied said it would respond to the FDA warning letter.<\/p>\n \u2014Bad news keeps stacking up for Intercept Pharmaceuticals and its drug, Ocaliva, a treatment for the rare liver disease primary biliary cholangitis (PBC).<\/strong> On Dec. 12, the FDA issued a safety alert<\/a>, warning of the risk of serious liver injury in patients without advanced liver cirrhosis. The alert came one month after the FDA turned down<\/a> Intercept\u2019s application seeking full approval for Ocaliva, which won its accelerated approval in PBC in 2016. The FDA\u2019s rejection letter for the drug cited safety concerns. When Ocaliva first reached the market, it was the only FDA-approved second-line treatment for PBC. In the past year, drugs from Ipsen<\/a> and Gilead Sciences have each won accelerated approvals as new second-line therapies <\/a>for the rare disease.<\/p>\n Two weeks after the FDA turned down full approval of Ocaliva, the European Commission revoked<\/a> the conditional marketing authorization for the drug. Advanz Pharma holds rights to Ocaliva in Europe. The company said the commission decision is subject to an ongoing annulment procedure in the EU\u2019s General Court and a ruling is expected in 2025.<\/p>\n \u2014The FDA turned down<\/a> Zealand Pharma\u2019s glepaglutide as a treatment for short bowel syndrome, a rare disorder that develops when the small intestine is damaged or shortened, making it difficult for the organ to absorb nutrients.<\/strong> The drug is a long-acting GLP-2 analog intended to enhance the intestine\u2019s ability to absorb nutrients, reducing patients\u2019 dependence on intravenous feeding. According to Zealand, the FDA said the application needed more evidence of efficacy and safety. The company said it would discuss the letter with the FDA and proceed with plans to seek European approval in 2025.<\/p>\n \u2014Lexicon Pharmaceuticals came up short in its bid to expand approval of its drug, sotagliflozin (brand name Zynquista), to include the treatment of adults with type 1 diabetes and chronic kidney disease.<\/strong> The FDA\u2019s Dec. 20 rejection<\/a> of the drug followed a negative FDA advisory committee vote<\/a> in October. The FDA approved sotagliflozin last year as a treatment for heart failure<\/a>; it\u2019s marketed in this indication under the brand name Inpefa.<\/p>\n