Five weeks after getting a harsh thumbs down from the FDA for its multiple myeloma treatment, Pepaxto, Oncopeptides has delivered something of a parting shot—phase 3 results that show what the company calls in its press release a “clinical benefit” for the drug.
The data is from one of two confirmatory trials that the FDA halted after approving Pepaxto under its accelerated pathway in February of 2021 and then pulling the drug off the market after negative results from the other confirmatory study.
Oncopeptides CEO Jakob Lindberg said in an interview he assumes that the data isn’t enough for the FDA to reconsider its position. Yet, he noted that he remains confident that with the right trial design, the company can demonstrate the value of Pepaxto and eventually get it back on the market in the U.S.
The Lighthouse trial was designed to recruit 240 relapsed or refractory multiple myeloma patients, but when the FDA put a partial clinical hold on studies involving Pepaxto (melflufen) in July 2021, enrolment stopped after only 54 had been randomized. Then in February of this year, the trial was discontinued altogether.
The study is assessing Pepaxto when added to a combo of Johnson & Johnson’s Darzalex and the steroid dexamethasone in patients who have had at least three prior lines of therapy.
The progression-free survival—the trial's primary endpoint—was higher in the Pepaxto group compared to the Darzalex plus steroid control arm, but the company did not reveal the numbers.
“It’s harder and harder with smaller numbers (of patients) to reach any statistical significance,” Lindberg said.
The FDA pulled Pepaxto, because results of the Ocean confirmatory trial indicated that the drug may cause patients to die early. That study compared Pepaxto plus dexamethasone to Bristol Myers Squibb’s Pomalyst plus dexamethasone.
The death rate for Pepaxto was 47.6% versus 43.4% for Pomalyst, while the median duration of survival was 19.7 months versus 25 months, respectively.
The Swedish biotech countered that a subgroup analysis showed that Pepaxto still had value, pointing to positive results when eliminating a key patient group—those who had undergone stem cell transplants within the last three years. The company also maintained that age is a major separator, with Pepaxto performing better in older patients and Pomalyst the superior option for those who are younger.
This June, Europe bought the explanation, signing off on Pepaxti, as it is known there. Two weeks ago, the company launched the drug in Germany and Austria at a monthly price of 10,900 euros ($10,837). Negotiations are ongoing with other countries in Europe.
In September, Oncopeptides’ subgroup approach didn’t go over as well with an FDA panel of experts, which voted it down 14-2.
While admitting the limitations of the Lighthouse study because of its size, Lindberg said that it does show that Pepaxto doesn’t shorten life expectancy. “We can certainly say there’s no risk of absolute (overall survival) harm,” Lindberg said. “It’s just statistically impossible.”