Johnson & Johnson, Legend's CAR-T Carvykti enters myeloma ring with FDA nod

An FDA approval for Johnson & Johnson and Legend Biotech’s CAR-T therapy may be three months later than originally expected, but it still came through for the partners. Having watched first-in-class Bristol Myers Squibb stumble with supply during its own CAR-T rollout, the two companies have devised a game plan to ensure a smoother launch.

Monday, the FDA greenlighted J&J and Legend’s CAR-T therapy Carvykti to treat multiple myeloma after four previous therapies. The label gives the drug, formerly known as cilta-cel, a level playing field against Bristol and bluebird bio spinout 2seventy bio’s rival BCMA-targeted CAR-T drug Abecma, which arrived a year ago as a fifth-line treatment.

J&J and Legend will jointly commercialize cilta-cel in the U.S. The pair is pricing the tailored cell therapy at a wholesale acquisition cost of $465,000, compared with Abecma’s $419,500 list price at launch.

Before the approval, Evaluate Vantage projected $1.7 billion for Carvykti's sales in 2026. J&J and Legend are more bullish, having pegged the drug’s peak sales at above $5 billion based on its potential to reach earlier lines of treatment, Legend CEO Ying Huang said during this year’s J.P. Morgan Healthcare Conference in January. By comparison, BMS has figured Abecma could reach over $1 billion in 2029.

So far in Bristol's launch, Abecma has hit supply constraints as the company struggles to meet demand. CAR-T therapies like Abecma and Carvykti are genetically engineered versions of a patient’s own T cells that target cancer cells. During the production process, viral vectors are used to introduce genetic material that encodes the CAR, which guides T cells. BMS is currently working with contract manufacturers to increase capacity for vectors.

RELATED: JPM 2022: J&J, Legend hope to avoid supply challenges that have ailed Bristol Myers' Abecma as cita-cel nears FDA nod

Having predicted the potential for strong demand, J&J and Legend have decided to bring manufacturing in house to ensure “long-term stability and reliability” of supply, Huang said at JPM. For Carvykti, J&J is responsible for making the lentiviral vectors.

Legend has also been prepping for the launch by building its cell therapy manufacturing footprint, Huang said. The company aims to have ample capacity by the end of 2022 or early 2023.

In the meantime, J&J and Legend don’t want to bite off more than they can chew. Rather than going big and bringing all the planned Carvykti treatment centers online right away, the partners are planning a phased launch, Mike Hirschmann, Legend’s U.S. commercial lead, said at JPM. The pair is launching Carvykti gradually in sites based on an algorithm that factors in population density.

“By being selective out of the gate, we can ensure that those sites who are brought on board have access to therapy,” Hirschmann said.

“One of the challenges we hear from our KOLs and our providers is, ‘I need certainty, I need to know if I’m going to have a slot this month and next month … because I have lines of people I’m trying to prepare for therapy,’” he explained.

RELATED: ASCO: J&J's anti-BCMA CAR-T pads its case ahead of speedy review and Bristol Myers showdown

Meanwhile, Carvykti appears to be more efficacious than Abecma. In the phase 2 part of the CARTITUDE-1 study, Carvykti shrank tumors in 98% of very sick multiple myeloma patients who had tried at least three prior lines of therapy, with 80% of patients seeing no sign of tumors, according to an update at 2021’s American Society of Clinical Oncology (ASCO) annual meeting. Another update in December with 22 months of follow-up found over half of patients in the clinical trial remained alive without disease progression.

“If we look in the literature right now, an 80% stringent complete response rate, to my knowledge, is the highest we’ve seen in any study—and that includes studies with newly diagnosed myeloma,” Mark Wildgust, Ph.D., vice president of global medical affairs, oncology, at Johnson & Johnson’s Janssen, told Fierce Biotech during ASCO.

By comparison, Abecma’s label describes a tumor response rate of 72% and 28% for complete tumor eradication. The median time Abecma patients had lived without tumor progression was 8.8 months in its own clinical trial.

But Carvykti has been linked to a higher rate of neurotoxicity, an issue Legend has attributed to a high tumor burden among patients. The company is pouring a lot of effort into education about enhanced bridging therapy to reduce tumor burden as well as early and more extensive management of cytokine release syndrome—a dangerous side effects of CAR-T therapies—with steroids and Roche’s Actemra, Lida Pacaud, Legend’s vice president of clinical development, oncology cell and gene therapy, said at JPM.

RELATED: Johnson & Johnson preps for first CAR-T launch with a new patient support program, a dedicated sales team and more

Much of the estimated $5 billion peak sales estimate hinges on Carvykti’s ability to move into earlier lines of treatment. There, J&J is running CARTITUDE-4 and CARTITUDE-5 trials. After implementation of the mitigation methods, early data on more than 200 patients treated across the CARTITUDE program showed only one case of neurotoxicity side effect, Pacaud said.

For CARTITUDE-4, which tests cilta-cel in patients who’ve received one to three prior lines of therapy, enrollment wrapped up in October. Given historical performance of existing standard of care, Pacaud suggested the trial might start to see a difference in efficacy after nine to 10 months of follow-up.

For J&J, cilta-cel marks the first approval for an expanding cell therapy pipeline. For Legend, the biotech has come a long way since it first wowed the biopharma world with the first cilta-cel data at 2017’s ASCO meeting and attracted J&J into the partnership that year. The company and its drug have since become a poster child for a China-developed therapy being recognized by a foreign Big Pharma company.