CD28 kills again? Mitch Gold’s plan to make cell therapy 2.0 history crashes after another patient dies of cardiogenic shock

24 Oct 2022
endpts.com
AntibodyCell Therapy
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.
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