Mitch Gold’s plans to push the envelope on cell therapy 2.0 has crashed into a fresh safety issue — and this time his biotech is ready to call it quits on the lead in-house effort.
Seven months after Alpine Immune Sciences’ davoceticept (ALPN-202) was sidelined by regulators after the death of a patient from cardiogenic shock, the biotech is back with fresh news of another death — also by cardiogenic shock.
The drug — a costimulator of CD28 — was being tested in Phase I as a monotherapy and in combination with the PD-1 star Keytruda. Like the first death, the latest fatality occurred in the combo study with pembro, in this case after a single dose of each drug.
A checkpoint 2.0 drug runs into trouble as Alpine gets hit with the latest in a string of clinical holds
Now Alpine will abandon the drug program and switch gears, turning to another therapy in the pipeline that they’re now claiming has best-in-class potential.
“Davoceticept has shown encouraging signs of clinical activity and it is unfortunate we have not yet been able to identify a safe dose regimen for the combination with pembrolizumab,” said Gold, best known for taking Dendreon to a high-profile approval for a drug now largely relegated to the margins.
Cell therapy has been bedeviled by safety issues from the beginning, but as cytokine release syndrome becomes more manageable to handle the second-gen players like
Tmunity
and
Allogene
and others have experienced a slate of issues that have kept the FDA on high alert on the safety front. Back-to-back deaths for the same cause in the same study sent a clear message that the investigators aren’t fully aware what the problem is, or how to prevent it. So for now, that’s one drug that will stay pigeonholed in the cul-de-sac of failure.
CD28 became a notorious target in oncology 16 years ago, when a company called TeGenero went after it with disastrous results. All 6 patients in the early-stage study nearly died, chilling the field considerably.
Just weeks ago, though, Regeneron’s George Yancopoulos
offered a full-throated cheer
for their PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo, which he believes has the chance of becoming the next big thing in immuno-oncology.