Sanofi's Sarclisa aims to emerge from J&J's multiple myeloma shadow after first-in-class win

Sanofi's Sarclisa has demonstrated significant promise in the treatment of first-line transplant-ineligible multiple myeloma, according to findings unveiled at ASCO24. When added to the standard treatment combination of Takeda’s Velcade, Bristol Myers Squibb’s Revlimid, and the steroid dexamethasone (VRd), Sarclisa reduced the risk of disease progression or death by 40% in newly diagnosed patients. This marks the first successful global phase 3 trial for a CD38 antibody in combination with VRd for this particular patient group.

Currently, Johnson & Johnson’s Darzalex dominates the anti-CD38 treatment market for multiple myeloma. Sanofi, however, aims to secure a competitive edge with Sarclisa’s encouraging trial results. Darzalex is already FDA-approved in a regimen with Revlimid and dexamethasone for a similar patient population, and J&J is now pursuing FDA approval for Darzalex-VRd in first-line, transplant-eligible myeloma. This indicates that Sarclisa, if greenlit, will face stiff competition from Darzalex in the transplant-ineligible setting, where Darzalex is already approved in a combination with Velcade, melphalan, and prednisone.

Sanofi selected the VRd regimen for Sarclisa's trial because it is considered a standard-of-care based on the outcomes of the SWOG 0777 study. Peter Adamson, Sanofi’s head of oncology development, noted that after nearly five years of follow-up, the median progression-free survival (PFS) for the VRd arm was 54.3 months. Sarclisa's regimen has not yet reached its median PFS, but trends suggest it could extend to around 90 months.

In terms of deep response, measured by minimal residual disease (MRD) negativity, 55.5% of patients receiving the Sarclisa-VRd combination achieved a complete response, compared to 40.9% for the VRd group. MRD negativity lasted for at least one year in 46.8% of the Sarclisa arm versus 24.3% in the VRd arm. Although overall survival data remains preliminary due to the chronic nature of multiple myeloma, the trends favor Sarclisa, with an estimated 72.3% of patients in the Sarclisa group still alive after five years, compared to 66.3% in the control group.

The FDA has accepted Sanofi’s application based on the IMROZ data and granted it priority review, with a decision expected by September 27, 2024. The IMROZ results were delayed from the initial timeline, which aimed for the end of 2021, due to improvements in myeloma care over time.

Sarclisa is currently administered as an infusion. Sanofi is developing a semi-automatic on-body device for subcutaneous delivery and a traditional manual injection. This new administration method could pose a direct challenge to J&J’s Darzalex Faspro.

Beyond IMROZ, Sarclisa is being examined in other first-line myeloma settings. The German GMMG-HD7 study is evaluating Sarclisa and VRd in transplant-eligible patients, with additional data expected later this year. This data could support a regulatory submission in 2025. Additionally, a European study called IsKia recently reported MRD analysis results for Sarclisa in combination with Amgen’s Kyprolis, Revlimid, and dexamethasone, also in transplant-eligible myeloma.

Following an FDA advisory committee meeting in April, there's potential for MRD to be recognized as a surrogate endpoint to expedite multiple myeloma drug approvals. Adamson stated that Sanofi is well-positioned if the FDA begins to allow MRD as an approval criterion, emphasizing the company’s rigorous data collection across trials to inform clinical decisions.

Sanofi is exploring how to use IsKia’s MRD data for regulatory approval, engaging in discussions with regulatory agencies on the best approach. While the data is robust, Adamson cautions against premature conclusions, underscoring the ongoing deliberations on the next steps.