The Food and Drug Administration on Monday approved a powerful new blood cancer treatment, clearing a personalized cell therapy developed by Johnson & Johnson and China's Legend Biotech for use in multiple myeloma.

The drug, which will be sold by the companies as Carvykti in the U.S., is the latest so-called CAR-T therapy to win FDA approval and the second for multiple myeloma. Built from patients' immune cells, CAR-T treatments are complex to manufacture and costly to administer, but can drive long-lasting remissions for some patients who have few or no other options.

Four CAR-T drugs are approved for certain types of leukemia and lymphoma, while the FDA in March granted an OK to Abecma, a CAR-T for multiple myeloma developed by Bristol Myers Squibb and 2Seventy bio. 

Together, Abecma and Carvykti represent a new class of treatment for multiple myeloma, one of the most common blood cancers, for which a slate of new medicines have become available in recent years.

The trial J&J and Legend used to support their approval application to the FDA enrolled nearly 100 people with multiple myeloma whose cancer had relapsed from or become resistant to at least three prior drugs.

Study results, which were last updated in December, showed nearly every patient treated with Carvykti responded. Eighty-three percent experienced a "stringent complete response," meaning no cancerous cells could be found in the blood or bone marrow, after a median follow-up of two years.

At that time point, 74% were still alive and 61% had not had their cancer progress further, both strong signs of Carvykti's efficacy and suggestive of a durable benefit to treatment.

As participants were very sick and had tried most or all alternative drugs, the study did not compare Carvykti therapy to a control group — a practice that's common in trials of cancer medicines for advanced disease. Other CAR-T therapies for leukemia and lymphoma, such as Novartis' Kymriah and Gilead's Yescarta, were also approved on the basis of results from "single-arm" trials.

J&J set Carvykti's list price at $465,000, higher than the $419,500 wholesale cost of Bristol Myers' Abecma. In an emailed statement, J&J said it anticipates the therapy being covered by most commercial insurers and by Medicare.

Other CAR-T drugs also come at exceptionally high costs, which their makers say reflect their clinical benefit as well as the intense manufacturing and logistical challenges in delivering a personalized cell therapy.

J&J and Legend will split costs and profits associated with Carvykti in the U.S. under a partnership deal they struck in late 2017. While currently available CAR-T therapies have only recently begun to gain traction commercially, J&J has set high expectations for Carvykti. The pharma predicts peak annual sales of greater than $5 billion, or about one-tenth of what its entire pharmaceutical business earned last year.

Getting close to those sales numbers will require J&J and Legend prove Carvykti is similarly effective in treating multiple myeloma at earlier stages, before patients have tried as many other drugs.

The companies have completed enrollment in another study, called CARTITUDE-4, that compares Carvykti to two other commonly used treatment regimens in multiple myeloma patients who have had between one to three prior drugs. A trial called CARTITUDE-5, meanwhile, is testing Carvykti against a three-drug regimen in people with newly diagnosed multiple myeloma who aren't going on to receive a stem cell transplant.

CAR-T competition

J&J and Legend will also have to compete with Bristol Myers and 2Seventy bio, which are planning a similar progression to earlier disease treatment with Abecma. Sales of Abecma totaled $164 million last year, although Bristol Myers has said it's facing supply constraints.

"We intend to compete in the market on the strength of the clinical efficacy" of Carvykti, said Ying Huang, Legend's CEO, in a January interview. "That's where we think we have an advantage."

Abecma also proved effective in clinical testing, with about three-quarters of tested patients experiencing a response. A little more than a quarter were judged to have had a stringent complete response. Comparing across trials can be challenging given differences in patient population and design, although both Abecma and Carvykti were tested in people with relapsed or refractory multiple myeloma who had received at least three prior drugs.

Treatment safety is another important consideration with CAR-T treatment, which can cause dangerous immune reactions and neurological toxicity — both risks that the FDA specifically warns against in Abecma and Carvykti's labeling.

In the main study of Carvykti, nearly all study participants had an immune response called cytokine release syndrome and a fifth had neurotoxicity. Only 4% and 9% of those cases were classified to be "Grade 3," or requiring aggressive medical intervention, both close to rates observed in testing of Abecma.

Carvykti's label also warns of the risk of Parkinsonian symptoms and Guillain-Barré syndrome, which occurred in several patients in clinical testing. 

Approval milestone

For Legend, Carvykti's approval is a milestone, coming nearly five years after the 2017 meeting of the American Society of Clinical Oncology, where startlingly positive early data took researchers by surprise.

A short six months later, J&J paid $350 million to partner with Legend on what would become Carvykti. J&J has since paid the biotech another $200 million in conditional payments based on development milestones the two partners have achieved.

Legend, which in China is based in Nanjing, now has more than 1,000 employees, including 450 in the U.S., where it will help J&J manufacture Carvykti.

That growth hasn't come without some turbulence, however. Legend's CEO Frank Zhang was arrested by Chinese authorities in November 2020 as a result of an investigation reportedly into import and export violations. Zhang was also at the time the chairman of Legend's parent company, Genscript.

Huang, who previously worked at Merck & Co. and as a biotech investment analyst, took over as Legend's CEO in September of that year.

For J&J, meanwhile, Carvykti expands its presence in multiple myeloma, for which it currently sells the widely used drug Darzalex. In addition, J&J is developing two other dual-targeting antibody drugs that are now in early- to mid-stage clinical testing.

Editor's note: This story has been updated to include references to Carvykti's labeling information from the FDA.