FDA approves Sarclisa regimen as first-line treatment for myeloma
Approved therapy now indicated for newly diagnosed patients in US
The U.S. Food and Drug Administration has approved Sanofi’s Sarclisa (isatuximab) in combination with standard-of-care treatment for adults with newly diagnosed multiple myeloma who are not eligible for a stem cell transplant.
Sarclisa was already approved in the U.S. as part of two other treatment regimens for patients with relapsed or refractory (treatment-resistant) multiple myeloma, known as RRMM. With the regulatory body’s new green light, the therapy has now earned its first indication for people who are newly diagnosed with multiple myeloma.
In this group, it will be used along with a standard first-line treatment regimen, known as VRd, that combines Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone.
“With [this] approval, doctors now have an important new option at their disposal that’s been shown to slow disease progression for longer compared to the current standard-of-care for adults living with newly diagnosed multiple myeloma who are not eligible for transplant in the US,” Brian Foard, executive vice president, head of specialty care at Sanofi, said in a company press release.
The decision makes Sarclisa the first anti-CD38 therapy in combination with the standard VRd regimen to be approved for newly diagnosed patients who are ineligible for an autologous stem cell transplant. While another anti-CD38 therapy, called Darzalex, is also approved for this indication, it is used with other treatment combinations but not with VRd.
Foard called the FDA’s decision “another momentous milestone” toward Sanofi’s goal of establishing Sarclisa “as a best-in-class therapy.” It also “expands the reach of this potentially transformative therapy to a larger population,” Foard said.
Expanded Sarclisa approval follows positive results from IMRIOZ trial
Delivered intravenously, or via infusion directly into the bloodstream, Sarclisa is an antibody designed to target the CD38 protein that’s found at high levels on the surface of myeloma cells, triggering their death.
The therapy was first approved in the U.S. in 2020 as part of a combination regimen with Pomalyst (pomalidomide) and dexamethasone for people with RRMM who received at least two prior lines of therapy, including Revlimid and a proteasome inhibitor. It was later cleared in 2021 in combination with Kyprolis (carfilzomib) and dexamethasone for RRMM patients who already have received one to three prior lines of therapy.
Earlier this year, the FDA agreed to review Sanofi’s application seeking Sarclisa’s label expansion to include treatment of the newly diagnosed patient population, also granting it priority review.
Included in that application were findings from the global Phase 3 IMRIOZ clinical trial (NCT03319667). That trial tested Sarclisa plus VRd against VRd alone in 446 newly diagnosed multiple myeloma patients who were not eligible for a stem cell transplant because of older age or simultaneous health conditions.
Trial data, published in June, demonstrated that Sarclisa plus VRd significantly lowered the risk of disease progression or death by 40% relative to VRd alone, meeting the study’s main goal.
Multiple myeloma is most frequently diagnosed in patients 65 years and older, yet the options for treatment in this population are limited due to a combination of age, frailty, and [simultaneous health conditions]. … The significant clinical benefit and improvements … demonstrated by the IMROZ [trial] regimen of [Sarclisa] plus VRd … make today’s approval an important moment for this vulnerable patient population and the larger multiple myeloma community.
After a median of nearly five years, patients in the standard care group lived without signs of disease progression, known as progression-free survival (PFS), for a median of 54.3 months, or about 4.5 years. PFS had not yet been reached in the Sarclisa group, meaning that not enough patients had experienced disease progression at that point to allow an estimate to be made.
Also, a significantly greater proportion of patients in the Sarclisa group achieved a complete response or better, meaning no detectable myeloma in blood or urine tests (74.7% vs. 64.1%), and achieved minimal residual disease (MRD) negativity (55.5% vs. 40.9%). MRD refers to the small number of myeloma cells that may remain after treatment and cause a relapse.
“Multiple myeloma is most frequently diagnosed in patients 65 years and older, yet the options for treatment in this population are limited due to a combination of age, frailty, and [simultaneous health conditions],” said Thomas Martin, MD, a professor of medicine at the University of California, San Francisco. “The significant clinical benefit and improvements … demonstrated by the IMROZ regimen of [Sarclisa] plus VRd … make today’s approval an important moment for this vulnerable patient population and the larger multiple myeloma community.”
Per the prescribing label, the most common side effects of Sarclisa when used in combination with VRd are upper respiratory tract infections, pneumonia, diarrhea, constipation, fatigue, and abnormal sensations related to nerve damage. Musculoskeletal pain, cataracts, or cloudy areas in the eyes, swelling on the extremities, rash, infusion-related reactions, insomnia, and COVID-19 also are listed on the prescribing label as among the most common side effects of the medication.
Meanwhile, Sanofi is still working on advancing Sarclisa’s clinical development program, according to the company. A number of Phase 2 and Phase 3 studies are underway to evaluate the therapy for six other possible indications in multiple myeloma. The company also is testing a new subcutaneous, or under-the-skin, formulation of Sarclisa.
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