2 Janssen therapies for RRMM earn positive opinion from EU committee
Antibody-based cancer therapy Talvey recommended for approval in EU
A European Medicines Agency committee has recommended that one antibody-based cancer therapy from Janssen Pharmaceuticals be approved for the treatment of relapsed and refractory multiple myeloma (RRMM), and that a second — one already with approval in the European Union for RRMM — be cleared for a less-frequent dosing regimen, the company has announced.
Talvey (talquetamab), an experimental therapy for heavily-treated RRMM patients, was granted a positive opinion by the Committee for Medicinal Products for Human Use, known as CHMP. The committee recommended that the antibody-based therapy be conditionally approved for adults with RRMM who have received at least three prior therapies but still showed disease progression on the most recent cancer treatment.
Additionally, the CHMP issued a positive opinion on a new dosing regimen for the approved therapy Tecvayli (teclistamab) that would require fewer doses. The advisory body recommended that it be cleared for RRMM patients who have achieved a complete response or better for at least six months.
An opinion by the CHMP is used by the European Commission when making a final decision about whether or not to approve a medication for a certain indication. While such decisions are not necessarily aligned with the CHMP’s recommendation, they often are — which is a positive sign for Talvey.
“We look forward to working with health authorities to bring [Talvey] to patients in need across the region as soon as possible, while we continue our focus on enhancing a robust multiple myeloma portfolio of therapeutics and regimens,” Edmond Chan, MD, senior director of Janssen’s EMEA therapeutic area lead hematology, said in a company press release.
Awaiting final trial results for antibody-based cancer therapy Tecvayli
In the EU, Janssen is seeking Talvey’s approval — now recommended by the CHMP — as a cancer therapy for individuals with RRMS who show progressing disease despite having received at least three prior treatments, including an immunomodulator, a proteasome inhibitor, and an anti-CD38 antibody.
“With [Talvey], a novel bispecific antibody targeting GPRC5D, we look to build on our legacy of innovation and bring forward a vital new treatment option for patients with relapsed and refractory multiple myeloma, who have a poor prognosis,” Chan said.
Janssen’s Tecvayli, meanwhile, is an antibody-based therapy already conditionally approved in both the U.S. and the EU for patients with the same type of cancer Talvey aims to treat.
Tecvayli’s U.S. approval was granted in October 2022 for patients who have received at least four prior lines of therapy for RRMM. Full approvals are pending final results from ongoing trials.
In Europe, its approved regimen comprises once-weekly subcutaneous or under-the-skin doses. The new dosing schedule now under review reduces the frequency to every other week for patients showing a complete response with the standard regimen.
“Pending approval, this variation for [Tecvayli] will be an important step forward … offering flexible, less frequent dosing depending on a patient’s response,” said Sen Zhuang, MD, PhD, vice president of clinical research and development at Janssen.
Talvey, Tecvayli both designed for hard-to-treat myeloma
Both Talvey and Tecvayli are bispecific antibodies, meaning that they’re designed to have two different targets in the body. Both target a protein found on myeloma cells as well as one on T-cells, the immune cells with cancer-fighting abilities.
Such therapies essentially work as a bridge between T-cells and myeloma cells to promote the death of cancer cells.
Talvey specifically binds to GPRC5D, a protein found largely on myeloma cells, but not healthy cells, as well as the CD3 protein on the surface of T-cell cells.
Janssen has submitted requests for Talvey’s approval as a single therapy for RRMM patients in both the EU and U.S. Those applications were based on data from the Phase 1 (NCT03399799) and Phase 2 (NCT04634552) portions of the ongoing MonumenTAL-1 trial.
Two optimal subcutaneous injection doses — 0.8 mg/kg once every two weeks or 0.4 mg/kg every week — were identified in the trial’s first part and tested in 339 RRMM patients in its Phase 2.
Over a median follow-up period of about 1-1.5 years, more than 70% of patients at either dose achieved a treatment response, meaning signs of their cancer shrunk or disappeared, according to recently presented data.
The most commonly reported side effects included cytokine release syndrome — a potentially life-threatening complication of immunotherapies — altered sense of taste, and skin-related disorders.
[The CHMP’s] positive recommendations for [Talvey and Tecvayli], two novel bispecific antibodies discovered and developed at Janssen, reinforce our commitment to delivering innovative treatment options for patients with multiple myeloma.
Tecvayli, a bispecific antibody targeting the BCMA protein on myeloma cells and CD3 on T-cells, originally earned conditional approval in the EU based on available data from the Phase 1 (NCT03145181) and Phase 2 (NCT04557098) portions of the ongoing MajesTEC trial.
The Phase 1 part of MajesTEC identified a recommended injection dose of 1.5 mg/kg weekly for its Phase 2 part. As of January, 165 RRMM patients had received that dose, 104 of whom — 63% in all — were considered treatment responders.
Patients achieving a partial or better response after four treatment cycles in Phase 1, or a complete response or better for at least six months in Phase 2, were able to switch to an every-other-week dosing schedule. If they continued to show good responses, these individuals could wean to dosing once every four weeks, or roughly once per month.
Data indicated that 63 patients switched to every-other-week dosing, and nine subsequently moved to once-monthly dosing. After a median follow-up of about a year following switching, 68.7% of patients remained treatment responders for two or more years since the time of first response.
The onset of serious infections was lower in treatment responders who switched to a less frequent dosing regimen, the team noted.
Given these findings, the CHMP has recommended the approval of a 1.5 mg/kg every-other-week dosing regimen for patients who have maintained a complete response or better for at least six months.
“[The CHMP’s] positive recommendations for [Talvey and Tecvayli], two novel bispecific antibodies discovered and developed at Janssen, reinforce our commitment to delivering innovative treatment options for patients with multiple myeloma,” Zhuang said.
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