ASCO: With first-in-class win, Sanofi's Sarclisa looks to step out of J&J's multiple myeloma shadow

2024-06-03

临床3期临床结果优先审批上市批准加速审批

来源: FiercePharma

Sanofi's Sarclisa, when added to a standard treatment regimen, reduced the risk of progression or death by 40% in first-line transplant-ineligible multiple myeloma, according to data presented at ASCO24.

In the field of anti-CD38 treatment for multiple myeloma, Johnson & Johnson’s Darzalex casts a long shadow. Now, Sanofi hopes a first-in-class win will help its Sarclisa gain an edge.

The addition of Sarclisa to the combination of Takeda’s Velcade, Bristol Myers Squibb’s Revlimid and the steroid dexamethasone (VRd) reduced the risk of progression or death by 40% in patients with newly diagnosed multiple myeloma who were ineligible for a stem cell transplant. For the trial, VRd served as the comparator arm.

As Sanofi pointed out, the readout from the phase 3 IMROZ trial marks the first positive global phase 3 trial for a CD38 antibody in combination with VRd in this transplant-ineligible population.

Meanwhile, J&J’s Darzalex already holds an FDA approval as part of a cocktail with Revlimid and dexamethasone in the same patient population, and J&J is seeking the FDA’s blessing for Darzalex-VRd in first-line, transplant-eligible myeloma.

That means Sarclisa, if approved, would likely face intense competition from Darzalex in the transplant-ineligible setting. There, the J&J drug is approved in a combo with Velcade, melphalan and prednisone. And given the different drugs available for myeloma, doctors often adopt various combinations, sometimes off label.

Sanofi picked VRd as Sarclisa’s trial combo partner because it’s considered a standard-of-care treatment regimen based on the results of the SWOG 0777 study, Peter Adamson, Sanofi’s head of oncology development and pediatric innovation, explained to Fierce Pharma in an interview.

After a median follow-up of nearly five years, the VRd arm’s median progression-free survival (PFS) result was reached at 54.3 months. The Sarclisa regimen has not reached its trial median PFS yet. Based on the current trend, investigators estimate the Sarclisa combo’s median PFS will reach around 90 months.

In terms of a deep response measuring the presence of minimal residual disease (MRD), 55.5% of patients who received the Sarclisa-VRd combo achieved a complete response that’s MRD negative, compared with 40.9% for the VRd group. MRD negativity lasted for at least a year in 46.8% and 24.3% of patients in the two arms, respectively.

Overall survival data remained immature given the chronic nature of myeloma, but the figures are trending in Sarclisa’s favor, Adamson said. After five years, investigators estimated that about 72.3% of patients in the Sarclisa arm were still alive, versus 66.3% in the control group, he said.

Based on the IMROZ data, the FDA has accepted Sanofi’s application and granted it a priority review. The agency is expected to make an approval decision by Sept. 27, 2024.

The IMROZ readout came way behind Sanofi’s original schedule, which was by the end of 2021. The development timeline extended as the care for myeloma improved over time, Adamson said.

Sarclisa is currently given as an infusion, and Sanofi is working on a semi-automatic on-body device to deliver the antibody drug under the skin, as well as a traditional manual injection, Adamson said. A subcutaneous version of Sarclisa would be a direct threat to J&J’s Darzalex Faspro.

Besides IMROZ, Sarclisa is being evaluated in other first-line myeloma settings. A German study coded GMMG-HD7 is assessing Sarclisa and VRd in transplant-eligible patients and in 2021 reported MRD data. Sanofi expects additional data from the trial later this year for a potential regulatory submission in 2025.

Separately, a European study called IsKia recently reported its MRD analysis for Sarclisa’s combination with Amgen’s Kyprolis, Revlimid and dexamethasone, also in transplant-eligible myeloma.

Following an advisory committee meeting in April, the FDA looks poised to open up MRD as a surrogate endpoint to enable accelerated approvals of multiple myeloma drugs.

Adamson said Sanofi is “well positioned” if the FDA starts to allow MRD as an approveable endpoint.

“Collection of time points for MRD has been our standpoint across trials,” the Sanofi exec said. “We know […] clinicians want that data. We have done a very rigorous job in ensuring that we have as complete a dataset as possible for those time points, to help inform decisions, to help better interpret our data.”

As to whether Sanofi will use IsKia’s MRD data to file for an approval, Adamson said the company will be “exploring and discussing with the regulatory agencies—how best can we utilize this data to inform a decision.”

“I think all of that is on the table, right? This is still pretty fresh for us,” Adamson said. “The data are quite strong, but we don’t want to get ahead of ourselves.”