Dive Brief:
- A CAR-T treatment from Adicet Bio has shown in human testing the potential to drive lupus into remission, providing early but notable evidence that therapies like it could be useful in treating autoimmune conditions.
- After a year of follow-up in an early-stage trial, 50% of lupus nephritis patients treated with Adicet’s therapy and evaluable for efficacy had a “complete” kidney response to treatment and 54% met a widely used statistical criteria for remission. All of those patients, who had previously tried multiple other treatments, stopped using immunosuppressive drugs.
- Adicet also noted that there were no serious cases of cytokine release syndrome or instances of neurological side effects, both of which are concerns with cell therapy treatments. The company intends to start up a pivotal study in lupus in the fourth quarter.
Dive Insight:
CAR-T treatments originally developed for cancer have been repurposed in recent years against autoimmune conditions. Early research has shown they might be able to “reset” the immune system by wiping out errant cells driving many of those diseases. But many of those medicines are personalized treatments that might be impractical in treating immunological diseases. They also carry the risk of potentially life-threatening side effects.
Those limitations were showcased a few weeks ago, when Novartis and Bristol Myers Squibb halted trials of individualized CAR-T therapies after witnessing worrisome side effects in testing. Novartis, for instance, said multiple treatment recipients had died following complications from a rare immune reaction.
Adicet believes it may be able to sidestep these issues with a different kind of treatment. Its therapy “prula-cel” is derived from the cells of donors, an “allogeneic” approach that’s quicker and less costly to manufacture. The “gamma delta” T cells prula-cel is built on are also different than the “alpha beta” T cells Novartis, Bristol Myers and many others are using.
In an email to BioPharma Dive, Adicet CEO Chen Schor wrote that gamma delta cells “secrete fewer and lower levels” of inflammatory cytokines that could spark immune-related side effects. Early testing of prula-cel showed about a quarter of those on treatment experienced a mild or moderate form of CRS. Infections were reported in more than half of patients on prula-cel. Around 8% had infections that were deemed Grade 3 in severity or higher.
Though the results were from a small and early trial, the data also showed efficacy data that were “competitive [with] cell therapy and antibody comps,” wrote Jefferies analyst Dennis Ding. Peer cell therapy makers, by comparison, have shown complete response rates of about 40%.
The data is "impressive" and could encourage pharmaceutical companies to "start migrating toward more elegant solutions like gamma delta T cells" in treating immune conditions, Ding added.
“What excites us the most is the opportunity to potentially redefine the standard of care for lupus patients from a lifetime of chronic immunosuppressants and steroid treatment,” Schor wrote.
Still, shares in Adicet dropped 22% by mid-morning. The biotech’s value peaked in 2022 when its gamma delta CAR-T treatment first showed promise against cancer, but has lagged since.
Schor said the company intends to discuss with regulators the possibility of an expanded pivotal study of patients who don’t have lupus nephritis.
