Editor’s note: Welcome to Editors' (re)View, our editors’ takes on things going on in the pharma world that deserve some extra consideration.
EU rejects Amylyx ALS drug
This week, Amylyx Pharmaceuticals announced that the European Union's medicines regulator has once again declined to recommend a marketing authorization for the company's drug designed to address amyotrophic lateral sclerosis (ALS).
The drug, branded Relyvrio and approved by the FDA last year, combines generic compounds sodium phenylbutyrate and taurursodiol to prevent the premature degeneration of nerve cells in the brain and spinal cord. The drug has also been conditionally approved in Canada.
ALS, commonly known as Lou Gehrig's disease, is a condition that deteriorates nerve cells in the brain and spinal cord, ultimately resulting in progressive muscle paralysis and fatality. According to the ALS Association, it affects over 30,000 patients in the U.S.
The EU's decision followed Amylyx's formal request for a re-examination of the initial negative opinion issued by the EMA's Committee for Medicinal Products for Human Use (CHMP) back in June. In response to the latest setback, the company has decided to concentrate on concluding the late-stage study of the drug, with plans to subsequently pursue EU approval.
— Andrea Corona
What’s going on with Alvotech's Reykjavik facility?
This week, we reported that the U.S. FDA rejected Alvotech's application to market a biosimilar version of J&J's arthritis therapy, Stelara. It’s not great news for the Iceland-based biotech, but the company seems to have seen it coming. The CRL for Alvotech's AVT04 application cited deficiencies that were conveyed following the FDA’s March 2023 inspection of the company’s Reykjavik facility — the same inspection that also triggered the rejection of Alvotech's Humira biosim.
In fact, Alvotech's Teva-partnered Humira biosimilar, AVT02, was rejected three times due to issues at the plant. Alvotech had been in a lawsuit tug-o-war with AbbVie over the biosim, with Alvotech accusing AbbVie of employing a “wrongful monopoly” on the drug and AbbVie later accusing Alvotech of recruiting one of its manufacturing execs to steal Humira trade secrets. The companies finally reached an agreement last year.
But Alvotech’s legal wins could be wasted if the company can’t fix its manufacturing issues. The problems started during a March 2022 FDA inspection. Following the inspection, the company was handed a 483 listing 13 observations, including mold and microbial excursions, as well as issues with the sterility of stoppers used in packaging. A year later, the facility was reinspected and again handed a 483 — this time with 8 observations. The second 483 cited different lapses, such as insufficient written quality procedures, issues with quality control records security and problems with container closure integrity.
The facility in question was only just opened in June 2016 and is consistently described by the drugmaker as “state of the art.” The plant, which features fully automated vial and syringe filling capabilities as well as quality control labs, uses single-use technology to “eliminate the risk of cross-contamination.”
Two consecutive failed inspections from an aging outdated facility wouldn’t surprise me, but it's less expected from a new facility. (I haven’t been able to find detailed public commentary from the company getting into the details, either.) But it appears that the FDA plans to reinspect the facility at the beginning of next year, so hopefully Alvotech can resolve the plant’s issues and ultimately help speed availability of more affordable biologics to patients. —Karen Langhauser