Tecvayli-Darzalex Faspro combo up for approval in 2 nations for treating RRMM
J&J regulatory filings in US, Brazil based on 'unprecedented' trial results
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Johnson & Johnson (J&J) is asking the U.S. Food and Drug Administration (FDA) to approve a combination of two medications, Tecvayli (teclistamab) and Darzalex Faspro (daratumumab and hyaluronidase-fihj), for people with relapsed or refractory, or treatment-resistant, multiple myeloma (RRMM).
The regulatory submission was based on what the developer, in a company press release, called “unprecedented results” from a Phase 3 clinical trial that’s testing the combo — as a possible standard of care treatment — in more than 500 people with RRMM.
J&J said its application is being reviewed through the FDA’s Real-Time Oncology Review (RTOR) program, which enables the agency to begin reviewing clinical data before a full regulatory application is formally submitted. The company said it has also submitted a similar application to regulatory authorities in Brazil.
Earlier this week, based on the “strong” clinical trial results, the FDA awarded a Commissioner’s National Priority Voucher to the Tecvayli plus Darzalex Faspro combination, according to an agency press release. This pilot program, announced in June, aims to recognize treatments with the potential to deliver meaningful benefits for patients. It accelerates the review timeline to approximately 1-2 months.
According to the developer, the Tecvayli-Darzalex Faspro combo “led to a statistically significant progression-free survival and [an] overall survival advantage” among RRMM patients in the Phase 3 MajesTEC-3 trial (NCT05083169).
“With Tecvayli plus Darzalex Faspro we have the potential to set a new standard of care once again for this disease,” said Sen Zhuang, MD, vice president of oncology clinical research at J&J Innovative Medicine.
J&J’s applications in both countries are mainly based on the positive results seen in MajesTEC-3. Full findings from that trial were detailed in “Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma,” a paper recently published in The New England Journal of Medicine.
“With these data, we are entering a new era in treating multiple myeloma with the first bispecific combination to demonstrate superior overall survival as early as second line,” Zhuang said. “Alongside the other transformational therapies in our leading portfolio, we can offer patients optimal outcomes at any stage of disease – bringing us closer to our ultimate ambition to find a cure.”
Over 80% of patients still alive nearly 3 years after starting combo
Multiple myeloma is a form of blood cancer that develops due to the uncontrolled growth of immune cells in the bone marrow. Although a range of therapies are available, in many patients the cancer either fails to respond to initial treatment — and is thus dubbed refractory — or responds at first but then comes back, or relapses. Patients with relapsed or refractory disease are said to have RRMM.
Darzalex Faspro, which contains an antibody that targets a myeloma cell protein called CD38, is approved as part of various regimens for people with newly diagnosed myeloma and for RRMM patients who’ve had various prior lines of therapy. Tecvayli, meanwhile, is approved in the U.S. to treat people with RRMM who have received at least four previous lines of treatment. It works by simultaneously binding to BCMA, a protein found on myeloma cells, and CD3, a protein present on cancer-killing immune cells called T-cells, with the aim of triggering these immune cells to kill the cancer cells.
Maria-Victoria Mateos, MD, PhD, a physician at the University Hospital of Salamanca in Spain, who has provided consulting, advisory, and speaking services to J&J, said the two therapies “work synergistically by uniquely targeting both BCMA and CD38 to prime and activate the immune system.”
According to Mateos, using them as a combination treatment for people with RRMM “has the potential to change the standard of care.”
The MajesTEC-3 trial enrolled approximately 585 people with RRMM who’d had one to three prior lines of therapy. Some patients were treated with Darzalex Faspro and Tecvayli, while others received Darzalex Faspro in combination with dexamethasone and either Pomalyst (pomalidomide) or bortezomib (sold as Velcade and generics). These other combos are approved for early-line treatment of RRMM.
With a median follow-up time of nearly three years, 83.4% of patients treated with the Tecvayli-Darzalex Faspro combination were still alive and free from disease progression, the trial data showed. By comparison, fewer than 30% of individuals given the other treatment combinations were still alive and free from progression at the latest follow-up.
[This combination treatment] has the potential to change the standard of care [in RRMM].
Further, more than half of patients given the Tecvayli/Darzalex Faspro combo — and fewer than 20% of those given other treatments — were negative for minimal residual disease, essentially meaning they showed no detectable signs of cancer.
Early results of treatment often predicted long-term outcomes
J&J noted that the early results seen with the combo’s use tended to predict long-term outcomes: More than 90% of patients who did not show signs of progression after six months were still progression-free after three years.
Patients given the novel combo also tended to report better relief from myeloma symptoms and more improvements in quality of life than those given standard-of-care treatment, according to the researchers.
Safety data for the Tecvayli/Darzalex Faspro combo were overall comparable to safety data from approved regimens and in line with what’s expected from intensive cancer treatments. Almost all patients reported at least some side effects, with serious side effects in more than half. The most common serious side effects were low immune cell counts and infections; J&J noted that the risk of serious infections decreased after the first six months of the trial with the use of prophylactic (preventive) protocols.
Overall, Mateos said that the novel combination therapy “offers remarkable efficacy, a well-characterized safety profile with robust infection management protocols, and an opportunity to improve patient outcomes across academic and community settings.”
