Johnson & Johnson expects its cancer cell therapy Carvykti to become a go-to option for treating multiple myeloma earlier, presenting Monday a fuller look at clinical trial results that show the therapy substantially outperformed the current standard.
In the trial, Carvykti reduced the risk of disease progression or death by 74% versus one of two commonly used drug combinations in patients for whom a mainstay medicine called Revlimid no longer works. According to J&J, it’s the largest relative risk reduction to be reported in a Phase 3 study of a treatment for the blood cancer.
Fragments of the data leaked in April, when an abstract of the study was inadvertently posted online. On Monday, researchers are presenting detailed findings at the American Society of Clinical Oncology’s annual meeting.
The data hold up to the closer inspection, affirming Carvykti’s potential to be used after Revlimid fails, rather than reserved for only after several treatments do. J&J intends to use the data to seek an expanded approval, which would substantially broaden the cellular drug’s market.
“[Carvytki] has not only shown that it delivers remarkably effective outcomes compared to patients’ current options, but also that it can be used safely earlier in the treatment phase,” said Oreofe Odejide, a medical oncologist at Dana-Farber Cancer Institute, in a statement provided by ASCO.
J&J’s study, called CARTITUDE-4, enrolled 419 people with multiple myeloma that no longer responded to Revlimid. Some had received one or two other treatments in addition to Revlimid, too. Once enrolled, half received Carvykti after interim, or “bridging,” treatment with a cocktail of multiple myeloma therapies, while the other half received one of two three-drug regimens.
Overall, 84% of the trial participants assigned to receive Carvykti responded, seeing their blood cancer counts recede, compared to 67% given standard treatment. However, 32 people were not able to receive J&J’s drug, due to their disease progression or death. Of the 176 who actually did get the treatment, 175 responded — a 99% response rate.
Nearly four times as many people on Carvykti as on standard drugs achieved a measure of cancer response known as “minimal residual disease negative,” indicating no cancer cells were found after treatment.
“I think the data speak for themselves,” said Mark Wildgust, head of global medical affairs in oncology for J&J’s Janssen unit. “A single infusion significantly prolongs progression-free survival, and does so versus a highly effective standard of care.”
Binod Dhakal, an associate professor at the Medical College of Wisconsin and the study’s lead investigator, described the data in an ASCO press conference as “setting a new efficacy bar” in relapsed, refractory multiple myeloma.
Still, Carvykti does come with considerable side effects, including infections, low blood cell counts, neurological toxicity and a potentially dangerous immune reaction known as cytokine release syndrome, or CRS. Approximately three-quarters of participants who received Carvykti developed CRS, although notably only two cases were rated as severe.
Carvykti is what’s known as a CAR-T therapy. Made from the immune cells of each patient, these personalized treatments are engineered to target telltale proteins on the surface of cancer cells. In Carvykti’s case, it’s a protein known as BCMA.
J&J, which co-developed Carvykti with a biotechnology company called Legend, won U.S. approval of the drug in February 2022 for multiple myeloma patients whose cancer had relapsed or become resistant to at least four prior drugs.
The ASCO data should support earlier use, potentially after only one relapse, according to Wildgust. “CARTITUDE-4 should support an approval application in patients who have had one to three prior lines of therapy and are [Revlimid] refractory,” he said. “That represents a large portion of patients.”
Yet hanging over J&J’s expansion plans are manufacturing challenges that have constrained Carvykti’s availability in the U.S. Due to their personalized nature, CART- therapies are hard to produce, requiring an exacting supply chain and intensive processing before being infused into patients. Some components used to make them have been difficult to obtain in large quantities.
Since launching Carvykti, J&J has had to take a phased approach, allocating supply to a limited, but growing, number of treatment centers.
Meredith Unger, head of marketing and operations for Janssen’s U.S. CAR-T business, said the company has increased its supply substantially since the end of last year, allowing it to raise the number of allotted treatment slots per center by 50%.
Additionally, the company has begun to make additional slots available to centers if they have patients who need treatment before their next allocation, Unger said.
“We are working as hard as we can to get capacity going to meet demand, not only for the indications we’re approved for today, but [also] the indications we anticipate coming,” Unger said.
Carvykti shares the market with another CAR-T therapy, developed by Bristol Myers Squibb and sold as Abecma. Manufacturing challenges have also hampered Bristol Myers’ ability to supply the drug, although sales have grown in recent quarters.
Approved for late-line use, Abecma is currently under Food and Drug Administration review for earlier treatment in multiple myeloma patients who have previously received three commonly used types of drugs. A decision is expected by mid-December.
Beyond CAR-T, the pipeline of experimental multiple myeloma drugs being developed is deep, and includes two dual-targeting antibodies from J&J. People with the blood cancer often cycle through different treatments, which typically work for a time but aren’t typically curative.
Cell therapies could offer the potential for longer-lasting remission. At ASCO, J&J and Legend are also presenting follow-up data from two earlier studies of Carvykti and a precursor version of Carvykti, given later after many treatments had failed. Participants in one of the trials, dubbed LEGEND-2, lived a median of 56 months after treatment, while follow-up data from the second, CARTITUDE-1, showed nearly half of patients had no disease progression after three years.