Prulacabtagene Leucel

Adicet Bio is planning a pivotal study of its CAR-T cell therapy after half the patients who received prulacabtagene leucel (prula-cel) in a Phase I lupus study responded to treatment. The data come about two years after the company pivoted its cell therapy platform from oncology and into the autoimmune space. Despite the positive early findings, however, the company's shares fell close to 30% on Monday. 'Rapid and sustained' symptom reductionsAs of the Aug. 28 data cutoff, 22 study participants had evaluable data, including 16 patients with lupus nephritis (LN) and six with extra-renal systemic lupus erythematosus (SLE); all had at least six months of follow-up data, and 13 had one year or more. Each had received a single dose of prula-cel, an allogeneic, anti-CD20 gamma delta CAR-T. Prula-cel's design stands out amidst a wave of companies testing their anti-CD19 CAR-Ts in lupus and other autoimmune diseases (see – Spotlight On: A catalyst-rich year ahead for lupus).All patients discontinued immunosuppressants in the Phase I trial, Adicet said. Among those with 12-month data, half of LN patients experienced a complete renal response (CRR) and 54% achieved remission, based on Definition of Remission in Systemic lupus (DORIS) criteria. All but one patient recorded as a responder maintained their responses at 12 to 21 months of follow-up. According to Adicet, patients saw "rapid and sustained" reductions in the mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Physician’s Global Assessment (PGA), which were consistent with autologous CD19 CAR-T therapies. Of patients with 12 months of follow-up data, 85% achieved a PGA score below 0.5."Notably, these remissions were achieved off immunosuppression and were accompanied by biological evidence of an immune reset," said Lloyd Klickstein, Adicet's interim chief medical officer. "In a disease where chronic therapy with limited efficacy and significant tolerability and safety considerations remains the standard of care, the prospect of durable, treatment-free remission after a single treatment could be transformative for individuals living with lupus."On the safety front, Adicet reported that prula-cel was generally well tolerated and may be suitable for outpatient dosing. In the 24 safety-evaluable patients, there were no cases of immune effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) or graft vs host disease (GvHD), and no dose-limiting toxicities. About 25% of patients experienced grade 1 or 2 cytokine release syndrome (CRS), with no reports of grade 3 or higher CRS. Infections occurred in 54% of patients. "Combined with the FDA's support of outpatient administration of prula-cel, and the scalability of our off-the-shelf manufacturing, these findings support the potential of prula-cel to redefine the treatment expectations for patients living with systemic lupus erythematosus with or without lupus nephritis," said Adicet CEO Chen Schor. "We look forward to progressing towards a potentially pivotal study by the end of 2026."Next quarter, Adicet plans to start working on the pivotal study, the design for which it has already aligned on with the FDA. The single-arm trial will recruit "a double digit number of patients" with LN who had inadequate responses to at least two immunosuppressants, though it may expand to include lupus patients without nephritis given the DORIS remission rate findings reported Monday. The pivotal study's primary endpoint will evaluate CRR at 12 months. Adicet said it will share updated results for prula-cel in patients with LN and SLE in the middle of 2027, as well as systemic sclerosis data in the first half of next year.

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 Adicets 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 Squibbhalted 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 thats quicker and less costly to manufacture. The gamma delta T cellsprula-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 biotechs 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 dont have lupus nephritis. '