After receiving conditional and accelerated approval from the EC and FDA, respectively, talquetamab became the first-in-class bispecific antibody targeted to CD3 and GPRC5D to treat multiple myeloma.
It was approved based on the pivotal phase 1/2 MonumenTAL-1 trial for heavily pretreated patients with relapses or refractory (R/R) multiple myeloma. Ongoing phase 3 trials are expected to provide confirmation of clinical benefit in talquetamab’s approved setting and lead to label expansions in other multiple myeloma patient populations, including in combination with other approved agents (such as DARZALEX®, Johnson & Johnson Innovative Medicine). Talquetamab is poised as an important addition to the treatment armamentarium for this incurable, often-relapsing disease.
With the approval of talquetamab, Johnson & Johnson Innovative Medicine adds to its portfolio dedicated to addressing unmet needs for patients with multiple myeloma, with five innovative therapies including two bispecific antibodies. Talquetamab is an off-the-shelf, first-in-class, T-cell engaging, bispecific antibody targeted to CD3 and GPRC5D that is being investigated to treat multiple myeloma. Positive results have been reported from the pivotal phase 1/2 MonumenTAL-1 study conducted with patients who had previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. One-third of patients also received prior BCMA-targeted therapy. The study results showed the following:
MonumenTAL-3 is an ongoing phase 3 clinical trial evaluating talquetamab plus daratumumab with or without pomalidomide plus dexamethasone (compared with daratumumab plus pomalidomide and dexamethasone) in R/R multiple myeloma after at least one prior line of therapy.
January 2021
May 2021
August 2021
June 2022
August 2023
For patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 mAb
For patients with relapsed or refractory multiple myeloma who had received at least three prior therapies including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb and had demonstrated disease progression on the last therapy
Actual and expected launch:
Patents estimated to expire beginning in 2037
How will talquetamab impact the market for multiple myeloma?
Multiple myeloma is one of the largest therapy markets in oncology owing to treatment being dominated by combination regimens comprising premium-priced small molecule and biologic drugs. High treatment rates, many potential lines of treatment for R/R disease and long treatment durations for some regimens drive the large size of this market.
What gaps in treatment does talquetamab fill?
A large proportion of patients with multiple myeloma relapse and requires subsequent therapy. In addition, remissions become shorter as the disease progresses with each new line of therapy. Talquetamab has been approved to treat patients in this difficult-to-treat setting where most, if not all, treatment options have been exhausted, helping to fill a remaining unmet need for more efficacious therapies. As an off-the-shelf product, it also has an advantage over patient-specific CAR T-cell therapies, and it provides an option for patients who have progressed on an anti-BCMA therapy.
What hurdles might it need to overcome to reach blockbuster status?
Uptake could be hampered by the black box label for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Therefore, talquetamab is only available via the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS), in which prescribers must be certified. In addition, it may face stiff competition from other bispecific therapies.
– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023
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