Denali’s failure on Monday continues biopharma’s losing streak against amyotrophic lateral sclerosis. PTC Therapeutics and Amylyx have seen similarly disappointing results.
Nearly a year after its previous stumble in amyotrophic lateral sclerosis, Denali Therapeutics on Monday announced that its small molecule drug candidate DNL343 missed its primary and key secondary endpoints in the Phase II/III HEALEY ALS platform study.
The California biotech did not provide specific data in its news release, revealing only that DNL343 was unable to significantly slow disease progression versus placebo in patients with amyotrophic lateral sclerosis (ALS). HEALEY ALS measured disease progression as the change in disease severity and survival through 24 weeks.
DNL343 treatment likewise did not result in significant improvements in key secondary endpoints, including respiratory function and muscle strength. Safety outcomes were encouraging, with data showing that the drug candidate was well-tolerated.
Denali dipped almost 7% in after-hours trading on Monday to $18.40, down from $19.82 at the previous close.
CMO Carole Ho in a statement said that the biotech will continue to look forward to a more comprehensive assessment of the HEALEY ALS data—such as subgroup analyses and biomarker measurements, including neurofilament light chain levels—which are expected to “become available later in 2025.”
Despite the Phase II/III miss, analysts appear to be largely unworried about Denali’s prospects. In an investor note on Monday, Stifel’s Paul Matteis noted that HEALEY ALS “was a very high-risk/high-reward option, but Street expectations here were fairly low.”
Jefferies’ Michael Yee agreed, writing in a note that “it has historically been challenging to develop disease-modifying therapies for ALS.” HEALEY ALS’ design could have also contributed to the disappointing data, given that its “6-month endpoint was considered short to see separation of drug and [placebo],” Yee continued.
“The stock has traded down recently, but should be a buying opportunity for a better set up for the rest of the year,” Yee said.
Denali’s disappointing readout on Monday continues the industry’s losing streak in ALS. In February 2024, for instance, Denali reported that its Sanofi-partnered candidate DNL788 failed to significantly ease disease severity and boost functional performance in patients. In November 2024, PTC Therapeutics announced that it would no longer invest in its ALS hopeful utreloxastat after it failed the Phase II CardinALS trial.
Perhaps the most high-profile ALS miss came in March 2024 when Amylyx’s Relyvrio failed its confirmatory Phase III PHOENIX trial. The drug had been granted accelerated approval in September 2022, but the late-stage disappointment forced the Massachusetts biotech to pull Relyvrio from the market.
