Anitocabtagene autoleucel

Cell therapy developer Arcellx contends its lead program could be a safer alternative to currently available CAR T-treatments for multiple myeloma, noting that its previously reported preliminary data show the absence of worrisome neurological complications some fear could be associated with the broader therapeutic class. More detailed data presented at the American Society of Hematology annual meeting build on the safety profile of the Gilead Sciences-partnered Arcellx therapy, which some analysts now say has the potential to be best in its class. In a pivotal Phase 2 test of the Arcellx therapy, anitocabtagene autoleucel (anito-cel), 97% of patients responded to the one-time treatment. This study is evaluating anito-cel in patients who have had at least three prior lines of therapy. With a median follow-up of 9.5 months, 62% of patients achieved a complete response to anito-cel. On these efficacy measures, analysts say the results so far are comparable to Carvykti, the BCMA-targeting cell therapy marketed by Johnson & Johnson and Legend Biotech. But Arcellx could differentiate with better safety. One concern about Carvykti is the risk of parkinsonism, a movement disorder. In Carvykti’s clinical trials, parkinsonism was reported in 3% (eight of 285) of study participants. Five of those cases were classified as Grade 3 or higher. There was a delayed onset for this complication, which was observed weeks after administration of the therapy. The other available BCMA-targeting cell therapy is Abecma, from Bristol Myers Squibb and 2Seventy Bio. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech In the more than 150 patients dosed with anito-cel, Arcellx said there are no cases of parkinsonism so far, nor are there any reports of cranial nerve palsies or Guillain-Barré syndrome, a condition in which the immune system damages nerve cells. For anito-cel, better safety is in the therapy’s design. Autologous cell therapies are made by harvesting a patient’s immune cells and engineering them to go after a target. Arcellx engineers its therapies with a synthetic binding domain it calls D-Domain. D-Domain enables high expression of the chimeric antigen receptor for the target protein, which in the case of anito-cel is BCMA. But this binder is engineered in a way that reduces the risk of sparking an immune response. Better safety was one of the features that drew the interest of Gilead. Two years ago, Gilead paid Arcellx $225 million up front and made a $100 million equity investment in the biotech, beginning an alliance on anito-cel (known in earlier stages of development as CART-ddBCMA). Depending on the program’s progress, Arcellx could earn up to $3.9 billion in milestone payments. If anito-cel is approved, the two companies will share in commercialization of the therapy. For William Blair analyst Sami Corwin, the lack of any delayed neurological events in clinical testing so far is a key point of differentiation for the Arcellx therapy. In a note sent to investors, she said that while there were high rates of an excessive immune response called cytokine release syndrome, this complication is consistent with the entire class of CAR T-therapies and was manageable. One hurdle for cell therapy is manufacturing, which happens in a multi-step process that can take a month or more. Arcellx says it can offer a 17-day turnaround time for anito-cel leveraging the manufacturing infrastructure Kite has developed for its commercialized cell therapies. A panel of physicians speaking at an Arcellx investor event Monday evening noted that the rapid turnaround time improves the overall experience of CAR T-therapy for patients and clinicians. Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News The process of turning a patient’s immune cells into a living drug isn’t always successful, but Arcellx said anito-cell was successfully manufactured for 99% of patients in its studies. Kite, which produces the FDA-approved cell therapies Yescarta and Tecartus, claims a 96% commercial manufacturing success rate with more than 25,000 patients treated by therapies produced from a CAR T infrastructure that has more than 500 authorized treatment centers globally, including 150 centers in the U.S. Corwin noted that the smaller size of the D-Domain means it is more readily expressed by the engineered cells, which should enable consistent manufacturing of the end product at commercial scale. “We think Kite’s reputation as a CAR T leader and established network of [authorized treatment centers] will lend itself to a strong commercial launch for anito-cel in 2026, if approved,” Corwin said. Like Corwin, Leerink Partners analyst Daina Graybosch believes anito-cel has best-in-class potential, for safety as well as the manufacturing advantages that Gilead’s Kite division brings. In a research note, she described Kite as “head and shoulders above the field when it comes to cell therapy manufacturing and operational excellence.” However, Arcellx’s manufacturing is currently done by contractors Lonza and Oxford Biomedica. Graybosch said there’s some uncertainty about whether Kite can complete the technology transfer for the therapy in a timely manner and whether the speed and quality of the manufacturing will translate to anito-cel, particularly as the Arcellx therapy uses a lentivirus for delivery while Kite’s current therapies employ a gamma retrovirus. Arcellx is currently enrolling patients in a Phase 3 test of anito-cel. This study will evaluate the cell therapy in patients who have received one to three prior lines of treatment for multiple myeloma. The Phase 3 study will employ Kite’s manufacturing capabilities, Arcellx said in an investor presentation. Illustration from Arcellx IPO prospectus

SAN DIEGO — Gilead and Arcellx say their experimental multiple myeloma cell therapy anito-cel could be a safer rival to field leaders Legend Biotech and Johnson & Johnson. New results from a pivotal study of their therapy showed that of 86 patients who have previously tried at least 3 prior treatment regimens, 97% responded to treatment and 62% had a complete response at a median follow-up time of 9.5 months. The results are roughly in line with earlier data with a smaller group of patients released in an abstract last month. And Arcellx said there were no cases of Parkinsonism, cranial nerve palsies, and Guillain-Barré syndrome in 150 patients from both the Phase 1 and Phase 2 studies. About 10% of patients have those neurotoxic adverse events on Legend and J&J’s Carvykti, according to the drug’s FDA label . Physicians and analysts believe that if anito-cel keeps performing in clinical trials, it could become a preferred option to Carvykti. J&J and Legend have also struggled with manufacturing Carvykti, potentially creating another opening. “Patients can be in remission, but they can have these long-lasting side effects that are affecting the quality of life. So with anito-cel, not having this problem is very reassuring,” said Sandra Susanibar-Adaniya of the University of Pennsylvania, who was not involved in the study. “But I think we have to see, as more patients they get treated, if there are a different type of autoimmune or maybe CAR-related complications that will arise.” The new data were shared by Arcellx in a press release Sunday evening and presented Monday evening at the annual American Society of Hematology annual meeting. The Phase 2 study is now fully enrolled with 129 patients, Arcellx confirmed. Arcellx also reported that in a Phase 1 study of anito-cel with 38 patients, median progression-free survival was 30.2 months. In Carvykti’s larger pivotal study, the median progression-free survival was 34.9 months, though there are many limitations to making comparisons across different trials. Krina Patel, an investigator on the study and a myeloma physician at MD Anderson, said that while the overall response rate was similar to Carvykti’s pivotal study she thought it was still too early to say whether the therapies had about the same efficacy. Patel said that if the Phase 1 progression-free survival holds up in the Phase 2 study, then she would be confident that the efficacy is there. Better bridging therapies given before CAR-T can help with neuropathies and Parkinsonism, but not the nerve palsy, Patel noted. On safety, anito-cel resulted in mostly low-grade cases of cytokine release syndrome, a complication related to immunotherapies, but one patient died from CRS in the study. In addition, there were nine cases of ICANS — a form of neurotoxicity related to immunotherapies. In interviews with Endpoints News , J&J and Legend Biotech executives fiercely defended Carvykti. J&J called the effort to compare its drug with anito-cel “flawed given the stark differences in sample size, populations and follow-ups prior to the data being published.” Gilead and Arcellx have pointed to what they call the D-Domain on their CAR-T therapy, which is smaller compared to the binding proteins of the other multiple myeloma CAR-T therapies, including Bristol Myers Squibb’s Abecma, as a differentiating factor that gives the therapy a “fast off-rate.” “We obviously very firmly believe that is related to the binder and the technology,” said Arcellx CEO Rami Elghandour when asked what gives anito-cel its safety profile. However, to lead investigator Ciara Freeman of Moffitt Cancer Center, it’s unknown why Carvykti seems to cause certain neurotoxicities and anito-cel doesn’t. “Certainly all of that is really theoretical. And I think it’s unfair to comment on the scientific reasons why there are these differences — the underlying pathogenesis is so poorly understood,” said Freeman. Gilead and Arcellx expect anito-cel will be on the market in 2026 in the fourth-line setting. The companies also recently started a Phase 3 study called iMMagine-3 in patients who have received fewer previous treatments, where Carvykti won an expanded approval earlier this year. That study is being sponsored by and manufactured for by Gilead.