BioPharma, Pharma

Regulatory Roundup: Narcan’s Nod, an ALS Adcomm, FDA Holds Lifted & More

Narcan, a nasal spray product that reverses the effects of opioid overdose, is now FDA approved for non-prescription use. Other recent FDA approvals include decisions for drugs from Pharming Group, Incyte, and Aurion Biotech.

Opioid overdose can be quickly countered by a nasal spray administration of naloxone, a drug that reverses the depressive effects that opioids have on breathing and central nervous system function. But the product, available for more than seven years under the brand name Narcan, required a prescription. No longer.

The FDA this past week approved Narcan for over-the-counter, non-prescription use. The new approval follows a unanimous FDA advisory committee vote in February that the benefits of making Narcan over the counter outweigh the risks. The regulatory decision means that in addition to pharmacies, the nasal spray could soon be available for purchase in convenience stores, grocery stores, and even gas stations.

Narcan is the biggest seller for Emergent BioSolutions, but generic competition has started to erode sales of the prescription version of the product. The company reported $373.3 million in 2022 Narcan sales, down 14% compared to the prior year. The latest approval for Narcan could help bolster revenue, but Emergent has not yet disclosed a price for the OTC product. Emergent expects OTC Narcan will become available by late summer as the company changes its manufacturing to support nonprescription packaging and makes supply chain modifications.

The FDA and its counterparts in other countries have been busy. Here’s a recap of some other recent regulatory news:

Approved and Validated

—Pharming Group drug Joenja became the first FDA-approved treatment for a rare immune disorder called activated phosphoinositide 3-kinase delta syndrome, or APDS. The disease leads to low levels of white blood cells. Joenja is a small molecule that blocks the PI3K-delta protein, an approach intended to block the signaling pathways that lead to dysregulation of immune cells.

—Incyte welcomed a surprise cancer immunotherapy approval from the FDA. The agency greenlit the drug Zynyz as a treatment for Merkel cell carcinoma, a rare skin cancer. The approval comes as a surprise because the company had not previously disclosed a biologics license application or a target date for a regulatory decision. An application in squamous cell carcinoma of the anal canal was turned down by the FDA in 2021.

In Merkel cell carcinoma, Incyte’s new drug will compete against Keytruda from Merck and Bavencio, marketed from partners Pfizer and EMD Serono. Pfizer is pulling out of that alliance. EMD Serono announced this week it had regained global rights to Bavencio.

—The Japanese Ministry of Health, Labour and Welfare approved Incyte drug Pemazyre for treating myeloid/lymphoid neoplasms characterized by a particular genetic signature. This type of cancer is characterized by the overproduction of myeloid cells and it can progress to the blood cancer acute myeloid leukemia. The FDA approved Pemazyre for the myeloid/lymphoid neoplasms indication last August.

—Regulators in Japan also approved an Aurion Biotech cell therapy for bullous keratopathy of the cornea, a vision disorder affecting the innermost cells of the corneal endothelium. This therapy, brand name Vyznova, provides an alternative to corneal transplants that rely on a tight supply of donated corneas. Aurion’s technology was initially developed by scientists in Japan and then licensed by CorneaGen. That Seattle company formed Aurion Biotech, which last year raised $120 million to finance U.S. clinical trials of the cell therapy.

—The European Commission approved an Amicus Therapeutics drug for Pompe disease, a rare disorder in which patients lack a key enzyme called acid-alpha glucosidase. The enzyme deficiency leads to muscle weakness and a decline in lung function. Amicus will market its new product, an infusion, under the name “Pombilti.”

Amicus’s Pompe drug is part of a two medicine regimen. Prior to the infusion, patients must take a pill intended to stabilize Pombilti and improve its uptake by muscles. Amicus said it expects a European Medicines Agency committee will issue an opinion for the treatment’s pill component, called miglustat, in the second quarter of this year. Both drugs are still under FDA review.

—A Cidara Therapeutics antifungal received FDA approval. The affirmative regulatory decision for intravenously infused rezfungin, brand name Rezzayo, covers the treatment of candidemia and invasive candidiasis in adults who have limited treatment options for these infections. The drug is still under regulatory review in Europe. Rezzayo will be commercialized by Melinta Therapeutics, which acquired U.S. rights to the drug in 2021. Cidara licensed drug rights to Mundipharma for all other markets.

Dealing With Rejection

—Incyte’s approved myelofibrosis drug, ruxolitinib, failed to secure an additional approval for an extended-release formulation. According to Incyte, the FDA acknowledged that the study results met the goal of showing bioequivalence to the currently available version of the drug, marketed as Jakafi. Without disclosing specifics, Incyte said the FDA “identified additional requirements for approval.” The company said it plans to meet with the agency to discuss the next steps.

—The FDA rejected AbbVie’s application for its Parkinson’s disease treatment, ABBV-951. The drug/device combination product subcutaneously administers a solution of the prodrugs carbidopa and levodopa to treat the movement problems associated with Parkinson’s. According to AbbVie, the FDA asked for more information about the pump part of the product. No questions about safety or efficacy were raised, nor did the agency did not ask for another clinical trial. AbbVie said it plans to resubmit its application as soon as possible.

I Need Advice

—A Brainstorm Cell Therapeutics’ amyotrophic lateral sclerosis drug application that was sent back as incomplete will get a hearing in another forum—an FDA advisory committee. Last November, the FDA sent Brainstorm a refuse-to-file letter, telling the biotech that its application for the experimental ALS therapy, Nurown, needed more data. Prior to the submission of the biologics license application, the FDA recommended that the company run another clinical trial.

Brainstorm responded by asking the agency to review the application anyway, a procedure called “file over protest.” This step returns the application to active review. Brainstorm said it has submitted an amendment to the application that responds to most of the agency’s questions. The FDA said it will convene an advisory committee to weigh in on the application. The date for that meeting has not yet been set.

—An experimental Biogen drug for a rare form of amyotrophic lateral sclerosis caused by mutations to the SOD1 gene received a mixed recommendation from an FDA advisory committee. The drug, tofersen, is an antisense nucleotide designed to bind to and degrade SOD1 messenger RNA. Biogen has said trial results showing reductions in SOD1 protein and neurofilaments, filaments found in neurons that could be indicative of neurodegeneration, suggest the drug is slowing the disease’s progress.

The advisory committee voted unanimously that reduction in neurofilaments in the blood is reasonably likely to predict benefit in ALS patients who have the SOD1 mutation. However, on the question of whether the available clinical data provide substantial evidence of the drug’s effects on such patients, three members voted yes, five voted no, and one abstained. The FDA’s target date for a regulatory decision is April 25.

No Hold on Me Anymore

—The FDA lifted a partial hold that had been in place on a Phase 1/2 test of BLU-222, an experimental treatment for advanced solid tumors. The drug is designed to block CDK2, an enzyme that is associated with tumor growth. The FDA’s partial hold on the study was due to visual adverse events reported in some patients. The company said it will now work with study investigators to resume enrollment.

—Vigil Neuroscience had a partial clinical hold lifted on VGL101, an antibody drug in development for treating a rare leukodystrophy called ALSP. Though the FDA cleared the biotech to begin human testing of its drug in late 2021, the agency allowed dosing only up to 20 mg per kilogram of patient weight. The partial hold applied to doses higher than that limit. The company said the FDA lifted the hold on higher doses due to supporting data from the ongoing Phase 1 study.

Don’t Say I Didn’t Warn You

—The FDA issued a warning letter to a website hosted in Singapore selling ivermectin pills to U.S. customers for the unapproved use of treating Covid-19.

Photo: Justin Sullivan, Getty Images