Sarclisa approved in EU for adults new to MM and transplant ineligible
As in US, antibody part of combo therapy for newly diagnosed myeloma group
Regulators in the European Union (EU) have approved Sarclisa (isatuximab) in combination with standard-of-care medications for adults newly diagnosed with multiple myeloma who are not eligible for a stem cell transplant.
A CD38 inhibitor, it will be used with a first-line treatment regimen of Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone, often abbreviated as VRd.
The decision follows a similar one by U.S. regulators in September. Approval requests currently are under review in Japan and China.
As in the U.S. and many other countries, Sarclisa previously was approved in the EU as part of two other regimens for multiple myeloma patients with treatment-resistant disease — also known as relapsed/refractory multiple myeloma or RRMM, meaning their disease failed to respond to, or progressed after, other lines of therapy. The recent label expansion is the therapy’s sole indication as a first-line, or initial, treatment in newly diagnosed patients.
Sarclisa is widely used as combo therapy for relapsed-refractory MM
Sarclisa also is the first CD38 inhibitor to be approved in the EU for use with VRd in newly diagnosed patients, according to its developer, Sanofi.
“While there have been many important advancements in multiple myeloma treatment over the past decade, there remains a significant unmet need in the front-line setting, particularly for transplant-ineligible patients,” Olivier Nataf, global head of oncology at Sanofi, said in a company press release.“With today’s decision the 27 countries in the EU will have access to a potentially transformative new combination regimen, marking a significant step forward in our mission to make a meaningful difference in multiple myeloma treatment.”
Sarclisa, given via infusions into the bloodstream (intravenous infusions), belongs to a class of myeloma treatments called CD38 inhibitors. It’s an antibody designed to bind to CD38 — a protein found at high levels on the surface of myeloma cells — which ultimately triggers the death of those cells.
Sarclisa now has three approved indications in the EU for this rare cancer of the bone marrow, including two in RRMM.
For adults with RRMM, it’s approved in combination with pomalidomide (sold under the brand name Imnovid in the EU and Pomalyst in the U.S.) and dexamethasone after at least two prior lines of therapy that included Revlimid and a proteasome inhibitor, and whose cancer worsened after the most recent line. It’s also approved for use with Kyprolis (carfilzomib) and dexamethasone for adults after at least one line of therapy.
Sarclisa’s expansion to treat newly diagnosed adults was supported by data from the global, Phase 3 IMROZ clinical trial (NCT03319667), which tested Sarclisa with VRd against VRd alone in 446 patients, ages 18 to 80, newly diagnosed with multiple myeloma and not eligible for an autologous stem cell transplant due to their older age or other health conditions.
Better responses in newly diagnosed patients given combo in clinical trial
Trial results showed that Sarclisa in combination with VRd led to a significant, 40% reduction in the risk of disease progression or death relative to VRd.
Significantly more patients given the Sarclisa regimen achieved a complete response or better than the VRd group (74.7% vs. 64.1%) at five years or 60 months of follow-up, and more achieved both a complete response and negative status for minimal residual disease (MRD) than those with VRd alone (55.5% vs. 40.9%), trial researchers reported.
A complete response indicates there’s no sign of active cancer in standard clinical tests. MRD, measured with more sensitive tools, refers to the small number of cancer cells that can persist despite a complete response; these diseased cells can drive a relapse.
The combination treatment’s safety also was seen as comparable to VRd alone.
Sanofi now is sponsoring several clinical trials evaluating Sarclisa as a possible treatment for six other indications in multiple myeloma. The company also is working to develop an under-the-skin (subcutaneous) formulation of the therapy that could be less burdensome for patients.
Sarclisa given subcutaneously — using a delivery device that patients can wear or bring with them as they go about day-to-day activities — was found to be as equally effective as the intravenous infusion formulation in a clinical trial in adults with RRMM, Sanofi recently reported. It also indicated that it was planning to request approval of the subcutaneous formulation in the U.S. and EU this year.
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