Anitocabtagene autoleucel

Johnson & Johnson and Legend Biotech say their CAR-T therapy Carvykti has the potential to remove all traces of disease from certain blood cancer patients based on the latest results of a Phase 3 study. In the CARTITUDE-4 trial , a single infusion of Carvykti “significantly” increased rates of minimal residual disease negativity versus standard regimens, according to results presented Tuesday at the American Society of Hematology annual meeting in San Diego. The study enrolled more than 400 people with relapsed and lenalidomide-refractory multiple myeloma who had one to three prior lines of treatment. Nine out of 10 evaluable patients achieved MRD negativity with Carvykti, Mark Wildgust, head of global medical affairs for Johnson & Johnson Innovative Medicine, told Endpoints News in an interview. Half of the patients experienced sustained MRD negativity, which lasts for more than a year, he added. Carvykti secured its first FDA approval in 2022 for patients with relapsed or refractory multiple myeloma who had four or more prior treatments. In April, it won a label expansion to the earlier setting of lenalidomide-refractory patients with at least one or more previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent. The treatment pulled in $286 million in third-quarter sales, up around 87% from the same three-month period in 2023. Tuesday’s data add to long-term survival results from CARTITUDE-4 presented in September, which showed that 76.4% of Carvykti patients were still alive at a median of 34 months compared with 63.8% of patients on standard regimens. Taken together with the MRD negativity data, these results “change the conversation from treating to progression to treating to cure,” Wildgust said. J&J estimates that Carvykti could reach at least $5 billion in peak sales. But competition is on the horizon. On Monday, Gilead and Arcellx reported positive registrational data for their multiple myeloma candidate anito-cel, which they claim could be safer than Carvykti. Wildgust said the two treatments are not comparable, because Carvykti’s registrational trial enrolled patients who were more refractory at baseline.

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