Cenobamate

The FDA said it’s evaluating the need for regulatory action on Vyvgart Hytrulo after observing a potential signal of “severe worsening of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).” The FDA’s regular communications based on reports from its drug safety report database don’t always rattle investors’ cages. But that was not the case with a regulatory update Monday on argenx’s autoimmune disease star Vyvgart.In a quarterly update of data from the FDA Adverse Event Reporting System (FAERS), the FDA said it’s evaluating the need for regulatory action on Vyvgart Hytrulo after observing a potential signal of “severe worsening of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).”This is not just any safety signal, because CIDP is one of the very diseases that the injectable formulation of Vyvgart is approved to treat thanks to an FDA go-ahead a year ago. The FcRn blocker’s other U.S. indication is generalized myasthenia gravis (gMG).Vyvgart is projected to be a megablockbuster product, as analysts have generally pegged the autoimmune drug’s peak sales potential at above $10 billion. In 2024, Vyvgart’s sales jumped 84% year over year to reach $2.2 billion.The FDA’s announcement sent argenx investors to a short panic as the company’s stock price dropped as much as 9%—reaching its lowest level in about 11 months—before shares recovered most of the lost ground on Monday.In a statement to Fierce Pharma, argenx noted that the routine FAERS update does not change Vyvgart Hytrulo’s overall positive safety profile.“There has been nothing observed from an adverse event profile in the real world that changes the understanding of the benefit/risk profile of Vyvgart Hytrulo—it remains consistent with the label,” a spokesperson for the company said.Analysts from Citi, Jefferies, Leerink Partners and William Blair have all brushed off the impact from the safety update in their separate analyses. For one thing, the potential worsening of CIDP is not a new signal. In an article published in the Journal of the Neurological Sciences in January, two doctors at an Arizona-based neuroscience clinic reported four patients who experienced severe relapse of CIDP after switching from the original intravenous (IV) Vyvgart to the subcutaneous (SC) Vyvgart Hytrulo.Then, at the American Academy of Neurology 2025 meeting in April, argenx disclosed that 3.3% of the 1,316 CIDP patients treated with Vyvgart Hytrulo as of the end of January had shown some disease worsening, William Blair analysts noted. Overall, the rate of severe worsening among CIDP patients when transitioning treatment from IV to SC has been less than 2%, argenx noted in its statement to Fierce, citing the company’s own post-marketing surveillance data.In clinical testing, 5% of patients in the open-label “part A” portion of the phase 3 Adhere study experienced worsening of CIDP. But this issue was not listed as a common treatment-emergent adverse event during the subsequent randomized portion of the trial, Citi’s Samantha Semenkow, Ph.D., pointed out.This observation “suggests that worsening of disease tends to occur closer to initiation of therapy with Vyvgart Hytrulo,” the Citi analyst said.Both Semenkow and a team at Leerink cautioned that data from the FAERS system are difficult to interpret and have many limitations, including the lack of causality. For example, worsening of CIDP may simply be the result of ineffective treatment. In part A of Adhere, about a third of CIDP patients didn’t respond to Vyvgart Hytrulo.Real-world experience from doctors reflects a similar treatment discontinuation rate, according to Semenkow. One expert told the Citi analyst that three of his nine CIDP patients came off Vyvgart Hytrulo because of worsening of disease, but they were all successfully treated with the IV version.“Importantly, our KOL checks have not highlighted a safety concern with Vyvgart Hytrulo in CIDP,” Semenkow wrote. Despite the FDA communication, Jefferies analysts said they don’t expect any FDA action. By the team’s estimate, only about 10% to 14% of previous FAERS signals actually led to any label changes.“[T]o us, the worst case scenario is FDA may ask for monitoring language on label” regarding the rare cases of rapid worsening in CIDP, the Jefferies team said.The more important task for argenx, according to the William Blair team, is educating clinicians on how best to switch from IV to SC to potentially avoid disease worsening. The Dutch company is already conducting a phase 4 study of 25 patients testing initiating Vyvgart Hytrulo one week after the last IV infusion. The trial bears a primary completion date in September, according to clinicaltrials.gov. Other safety signalsIn addition to Vyvgart, the FDA on Monday also highlighted other safety information from its FAERS database that the agency is evaluating. These include cerebral venous sinus thrombosis among JAK inhibitors, vasculitis among PARP inhibitors, and liver problems with SK Biopharmaceuticals’ epilepsy drug Xcopri and Intercept Pharmaceuticals’ bile duct therapy Ocaliva.The agency also flagged a well-known safety signal of Eisai and Biogen’s Alzheimer’s disease drug Leqembi and other anti-amyloid therapies—amyloid-related imaging abnormality (ARIA)—for potential regulatory action. ARIA is already included on Leqembi’s label as a boxed warning, the highest safety alert of an FDA-approved drug.In a statement to Fierce Pharma, Eisai pointed out that safety information on FAERS does not equate to a causal relationship. Given that ARIA is a known risk of Leqembi, Eisai said new reports of the event are expected to be included in the FDA database.“Eisai and the FDA will continue to work together closely to thoroughly review post-marketing data as it is received,” the company said.