Sanofi’s Sarclisa Challenges Johnson & Johnson’s Darzalex: FDA Approves New First-Line Treatment, Targeting a $15 Billion Market!

Since its initial approval by the U.S. Food and Drug Administration (FDA) in 2020, Sarclisa, a drug made by Sanofi, has been specifically used to treat patients with multiple myeloma who have previously received other treatments. That changed on Friday. The FDA has approved Sarclisa in combination with Bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplantation.

With this expansion, Sarclisa will put some competitive pressure on Johnson & Johnson's Darzalex. Since 2018, Johnson & Johnson Medicine is the only CD38 antibody approved for the treatment of first-line myeloma. To gain approval for Darzalex, the FDA approved the drug in combination with Bortezomib, Mefaran, and prednisone, also for patients who are not candidates for transplantation. However, Darzalex's method of use is considered outdated and is not often used today.

Prior to the latest FDA approval, Sarclisa-VRd was recently added to the National Comprehensive Cancer Network (NCCN) myeloma treatment guidelines as the preferred protocol for patients not suitable for transplantation, along with VRd therapy alone and darzax-rd combination therapy. All three options are listed as the highest Category I recommendations.

"We are entering the largest segment of this market and we are leveling the playing field in a major drug category," Olivier Nataf, Sanofi's global head of oncology, said in a recent interview with Fierce Pharma.

Sarclisa-VRd has demonstrated its value as a new standard of treatment in the Phase iii IMROZ trial. Compared with VRd alone, the Sarclisa protocol significantly reduced the risk of disease progression or death by 40% in newly diagnosed, ineligible transplant patients.

Patients in the VRd group were free of disease progression for an average of 54.3 months in the study. Although Sarclisa's median progression-free survival (PFS) had not been reached at the time of the analysis, the researchers estimated that it would reach about 90 months.

darzax-Rd had a median PFS of 61.9 months versus 34.4 months for Rd, the latest analysis of the Phase 3 MAIA trial in newly diagnosed patients who were not suitable for transplantation.

Challenging Darzalex wasn't easy. In 2023, Johnson & Johnson Pharmaceutical's global sales increased 22% to $9.7 billion. By comparison, Sarclisa's revenue last year was $381 million, up 30 percent from the previous year. Still, Nataf believes the market is big enough for Sanofi to make its mark.

Citing estimates from appraisal firms, Nataf said it expects annual revenue from the CD38 class to reach $15 billion by 2028.

"We are one of only two," Mr. Nataf said.

While the use of Sarclisa-VRd in transplant ineligible patients marks Sanofi's first first-line treatment, Sanofi is moving toward a broader indication.

Sanofi said in August that in a German study numbered GMMG-HD7, Sarclisa in combination with VRd significantly improved PFS in patients with newly diagnosed myeloma eligible for transplant. According to Sanofi's most recent quarterly update, the study is intended to support regulatory approval of the application, which the company plans to file in the United States in the first half of 2025. NCCN guidelines have just made this combination an "alternative recommendation" for first-line transplant candidates. darzax-vrd is the preferred option there.

There are also Sarclisa in combination with Amgen's Kyprolis, lenalidomide and dexamethasone. In IsKia's Phase 3 clinical trial, the Sarclisa-KRd regimen significantly helped more transplant eligible first-line patients reach the deep tumor clearance threshold, i.e. minimum residual disease negative.

Although Sanofi has not announced regulatory plans for this use, the FDA appears poised to allow minimal residual disease as an alternative endpoint to accelerate approval of new myeloma therapies. In April, experts on an advisory committee unanimously supported the creation of this alternative endpoint, after two independent meta-analyses of past clinical trials showed it could predict long-term outcomes such as PFS.