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.


  1. Johnson & Johnson Innovative Medicine
  2. Bispecific antibody targeted to CD3 and GPRC5D
  3. Weekly or biweekly subcutaneous administration to treat R/R multiple myeloma
  4. ~105K R/R cases in the G7 markets in 2023

Why is it a drug to watch?

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:

  1. Biweekly dose after a median follow-up of nearly six months from first response:
  • 73.6% overall response rate (ORR)
  • 58% very good partial response (VGPR) rate and 33% complete response (CR) rate
  • ~85% of responders maintained response for at least nine months
  1. Weekly dose after a median follow-up of nearly 14 months from first response:
  • 73.0% overall response rate (ORR)
  • Median PFS of 8.2 months (vs 6.8 months with control)
  • 57% very good partial response (VGPR) rate and 35% complete response (CR) rate
  • Median duration of response (DOR) of 9.5 months

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.

Review and
approval status

January 2021

  • PRIME designation: EMA

May 2021

  • Orphan drug designation: U.S. FDA

August 2021

  • Orphan drug designation: EMA

June 2022

  • Breakthrough therapy designation: U.S. FDA

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

  • Accelerated approval: U.S. FDA

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

  • CMA: EMA

Actual and expected launch:

  • 2023: European Union, United States
  • 2025: Japan

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.

  1. The multiple myeloma market is expected to experience 5.9% annual growth in the major markets over the 2022-2032 period, driven by label expansions of currently approved therapies in combination with existing standards of care.
  2. Bispecific antibodies will reach major-market sales of $6.9 billion by 2032.
  3. Compared with the BCMA-directed bispecific T-cell engagers TECVAYLI™ (teclistamab; Johnson & Johnson Innovative Medicine) and ELREXFIO™ (elranatamab; Pfizer), talquetamab targets GPRC5D, providing an effective treatment option for patients who progressed on a prior BCMA-based treatment. Further, talquetamab has a more flexible dosing advantage than TECVAYLI.
  4. Expected label expansions for bispecific antibodies, including talquetamab, in combination with DARZALEX, with or without lenalidomide plus dexamethasone, will contribute nearly $4.5 billion in sales by 2032.
  5. As a subcutaneous-administered, off-the-shelf product, talquetamab is positioned at a competitive advantage over current and emerging CAR T-cell therapies in the R/R setting.
  6. Talquetamab has shown activity in patients with and without prior exposure to BCMA-targeted therapies (e.g., CARVYKTI™ [ Johnson & Johnson Innovative Medicine and Legend Biotech] and TECVAYLI); therefore, patients who have received prior BCMA-targeted therapies are not precluded from being eligible for talquetamab.

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.

expected sales in 2029
probability of success for talquetamab in Japan
Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drug Timeline &
Success Rates

– Source: Cortellis Competitive Intelligence, Drug Timeline & Success Rates Prediction current as of November 3, 2023

Drugs to Watch 2024

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