Another failed trial for Orphazyme's 'pipeline-in-a-product' leaves shadow on drug's future
The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.
In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.
Investors reacted accordingly to the news, as the $ORPH stock dropped 24.16% premarket to $6.41.
Orphazyme is a 1-drug company and has expectations that arimoclomol — dubbed its “pipeline-in-a-product” — has the ability to treat several different diseases. The company purchased the drug from CytRx in 2011 for $150,000 upfront, and the potential to make $120 million. But with that challenge has come repeated frustration as this is not the first time that the drug has flopped.
In March, the company announced that arimoclomol failed to hit its endpoints in Phase II/III trials for patients with inclusion body myositis, a debilitating muscle-wasting disease. The company also intends to advance arimoclomol into clinical development in Gaucher disease, the inherited disorder that causes sugar-containing fats to accumulate in the lysosomes of cells and affect the brain, bone marrow, spleen and liver. That program is currently in Phase II.
The drug just barely missed both primary endpoints in its Phase III Niemann-Pick disease type C study roughly 2.5 years ago. But the FDA accepted its application in September 2020 for the rare neurodegenerative condition and gave it priority review, reinforcing Orphazyme’s narrative that the FDA viewed the application favorably. There is no approved medicine for NPC, a rare disease that is estimated to impact 1 in 100,000 lives.
“We are disheartened by these results, as we had hoped arimoclomol might represent a viable new approach against the formidable challenge of this devastating disease,” CMO Thomas Blaettler said. “With over 18 months of evaluation, this trial represents one of the longest running clinical studies in this category. While unsuccessful, the data generated will contribute meaningfully to the scientific dialogue on this challenging disease.”
The PDUFA date for Niemann-Pick is June 17.
The company is in the midst of a tough stretch. In December 2020, then-CEO Kim Stratton resigned abruptly, and Orphazyme offered no explanation for the move other than that the choice was Stratton’s decision “following a dialogue initiated by the board of directors.”
The drug just narrowly missed its first primary endpoint on its 50-person Phase II/III NPC study back in January 2019. Scientists saw both a 74% reduction in disease severity and a p-value of 0.0506. Two pre-specified subgroup analyses reached significance, with disease progression slowing in patients over the age of 4 and in patients who had been taking an Actelion drug sometimes prescribed for the disease. But for this round of trials in ALS, the company did not release any data, leaving the public in the dark as to how it performed in the trial.
Topline data will be presented at the virtual European Network to Cure ALS meeting from May 12-14, the company said in a statement, while complete data will be published later in the year.
The randomized, placebo-controlled trial for ALS featured 245 at 29 sites across 12 countries in North America and Europe, the company said in its release. Patients either received 3 daily 248mg doses of arimoclomol or the placebo for up to 76 weeks.
The primary endpoint was to determine the efficacy through the combined assessment of function and survival, and the secondary endpoints included survival, ALS Functional Rating Scale-Revised and slow vital capacity.
Christophe Bourdon, Orphazyme CEO