Reports of seven deaths in patients who had taken Neurocrine Biosciences’ Vykat and the official termination of Aardvark Therapeutics’ Phase 3 trial after cardiac complications marked a tough day for the Prader-Willi syndrome community.
A group of clinicians have sounded the alarm after several deaths were potentially linked to Neurocrine Biosciences’ new treatment for the rare genetic disease Prader-Willi syndrome.
The Prader-Willi Syndrome Association (PWSA) on Tuesday posted a note to patients and caregivers warning of a new safety signal that has emerged since Neurocrine’s Vykat entered the market last year. A group of physicians cautioned that seven deaths and 100 serious adverse events have been recorded by the FDA’s Adverse Events Monitoring System, STAT News reported on Wednesday. The reports include instances of swelling, respiratory and heart complications.
Neurocrine opened trading on Wednesday down 2% to $158.51. Vykat came to Neurocrine through the $2.9 billion acquisition of Soleno Therapeutics in April.
“Potentially increased physician caution around prescribing and risk of regulatory scrutiny could limit uptake and constrain the product launch in coming quarters,” BMO Capital Markets wrote in a Wednesday morning investor note.
In a statement provided to BioSpace, Neurocrine said that the company is in close contact with the FDA, patient advocacy groups and prescribers about post-marketing surveillance as more patients get on treatment.
“VYKAT XR has a compelling risk-benefit profile in the context of a very serious disease,” the statement said. “Neurocrine conducted extensive diligence on the safety profile, including adverse event data, during our process to acquire Soleno.”
Prader-Willi syndrome is a rare disease that causes an insatiable desire to eat, plus a slow metabolism that can lead to significant weight gain. The condition can also cause cognitive disabilities and behavioral challenges.
The approval of Vykat marked a pivotal moment for the Prader-Willi community. “For many families it has brought a level of hope they have waited decades to see,” PWSA said in its recent statement. “At the same time, with every new treatment comes a responsibility to continue learning.”
BMO wrote that the serious events do not appear to have been revealed in clinical testing for Vykat. The Phase 3 pivotal trial that underpinned the FDA approval did show an elevated risk of swelling but these were listed as low severity events. There were no deaths reported in the trial.
“Today’s news on post-marketing surveillance comes as a meaningful surprise, but we reserve some caution in interpreting incidences as being directly linked to Vykat XR treatment given the absence of evidence establishing causality,” BMO said.
PWSA acknowledged that the new reports are concerning but stressed that they need to be taken in context and fully researched. The events have not yet been definitively linked to Vykat and involve patients with complex medical histories. “The reality is that people with PWS already face a higher risk of serious respiratory and cardiac complications throughout their lives,” the group said.
The reports could cause physicians to be more cautious in prescribing the medication, which could put pressure on Neurocrine, BMO noted. But the firm said the PWSA’s urging for “informed prescribing” rather than yanking the approval of Vykat was positive for the company.
“All in, we look to additional post-marketing safety updates to better assess potential implications to Vykat XR’s long-term risk-benefit profile and commercial trajectory,” BMO said.
Elsewhere in the Prader-Willi space, Aardvark Therapeutics has officially terminated a Phase 3 HERO trial of ARD-101 after reports earlier this year of cardiac concerns in the study, underscoring the challenging nature of the disease. The safety signal arose in healthy volunteers who were taking part in the study, spurring the FDA to place a clinical hold on the drug. That hold remains in place, according to Aardvark’s second quarter earnings report that was issued Tuesday.
“We believe the clinical risk of ARD-101 is elevated, as the cardiac events could be mechanism-based and call into question the therapeutic window of ARD-101,” William Blair wrote in a Wednesday morning note.
The company announced the termination of the study and said they are reviewing unblinded data now to determine next steps forward for ARD-101, William Blair said.
“Pending favorable data, these preliminary signals could better position Aardvark to design and conduct the second registration-enabling study,” the firm wrote.
The company is expected to announce more details after reaching alignment with the FDA on the next steps.
