Teclistamab

After receiving conditional and accelerated approval from the EC and FDA, respectively, teclistamab is the first-in-class bispecific antibody targeted to B-cell maturation antigen (BCMA) to treat multiple myeloma. It has been investigated and approved based on a pivotal phase 1/2 trial for relapsed or refractory (R/R) multiple myeloma patients who have received at least three (EC approval) or four (FDA approval) prior lines of therapy and experienced disease progression on their last therapy. Ongoing phase 3 trials are expected to provide confirmation of clinical benefit in teclistamab’s approved setting and lead to label expansions in other multiple myeloma patient populations, including in combination with other approved agents. Teclistamab is poised as an important addition to the treatment armamentarium for this incurable, often-relapsing disease.

About teclistamab

Janssen Pharmaceutical Companies of Johnson & Johnson
Bispecific antibody targeted at BCMA and CD3
Weekly subcutaneous injection to treat R/R multiple myeloma
~72,000 diagnosed incident cases of multiple myeloma in the G7 markets in 2021

Why is it a drug to watch?

Teclistamab is an off-the-shelf, first-in-class, T-cell redirecting, bispecific antibody targeted to BCMA and CD3; it is being investigated to treat multiple myeloma.

The European Commission (EC)’s conditional marketing authorization (CMA) supported by the European Medicine Agency (EMA)’s Priority Medicines (PRIME) designation and accelerated approval by the U.S. Food and Drug Administration (FDA) were based on positive results from the multi-cohort pivotal phase 2 (part 3) MajesTEC-1 study, which showed:
• 63.0% overall response rate (ORR) after a median five lines of prior therapy, 58.8% very good partial response (VGPR) rate and 39.4% complete response (CR) rate with 46% of patients who achieved a CR or better being minimal residual disease (MRD) negative (10-5);
• median PFS duration of 11.3 months and median OS duration of 18.3 months; and
• occurrence of adverse events at a level consistent for this patient population and with other therapies such as BCMA-targeted CAR T-cell therapy.
Ongoing phase 3 clinical trials are investigating the use of teclistamab in combination with other drugs:
• MajesTEC-3: phase 3 of teclistamab plus daratumumab in R/R multiple myeloma after one to three prior line(s) of therapy (i.e., second to fourth-line settings)
• MajesTEC-4: phase 3 of teclistamab plus lenalidomide as maintenance treatment in newly diagnosed multiple myeloma following autologous stem cell transplant (ASCT)
• MajesTEC-7: phase 3 of teclistamab plus daratumumab and lenalidomide in newly diagnosed multiple myeloma ineligible or not intended for ASCT as initial therapy
• MajesTEC-9: phase 3 of teclistamab plus pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in R/R multiple myeloma after one to three prior line(s) of therapy (i.e., second to fourth-line settings)
An application to the Medicare new technology add-on (NTAP) program was submitted for fiscal year 2023, based on the argument that teclistamab is dissimilar to other bispecific antibodies for this indication, satisfying the requirement for newness.

Review and approval status

June 2021:
• Breakthrough Therapy Designation: U.S. FDADecember 2021:
• BLA submission, priority review granted: U.S. FDA

January 2022:
• MAA submission: EMA

August 2022:
For patients with R/R multiple myeloma who have received at least three prior therapies (immunomodulatory agent, proteasome inhibitor and a CD38-targeted antibody) and demonstrated disease progression on the last therapy
• CMA: EC

October 2022:
For patients with R/R multiple myeloma who have received at least four prior therapies (immunomodulatory agent, proteasome inhibitor and a CD38-targeted antibody)
• Accelerated approval: U.S. FDA

Actual and expected launch:
• 2022: Europe and United States
• 2023: Japan

Patents estimated to expire beginning in 2036

How will teclistamab 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 therapies drive the large size of this market. The multiple myeloma market is expected to grow from $23.6 billion in 2021 to $35.3 billion in 2031.

Teclistamab is forecast to achieve sales of $1.8 billion in 2031, across the major G7 markets
Teclistamab is expected to hold approximately 4% of the first-line ASCT market and 5% of the R/R (second to seventh-line) multiple myeloma market in 2031 (across the G7 markets).
As a subcutaneous-administered, off-the-shelf product that can be combined with currently approved drugs and regimens to improve their efficacy, teclistamab is positioned at a competitive advantage to some other current and emerging therapies in the R/R setting.

What gaps in treatment does teclistamab fill?

Teclistamab has demonstrated deep and durable responses in patients with R/R disease, which indicates its potential to provide sizeable clinical benefit without significant adverse events. It has the potential to extend remissions and delay disease progression. Given that a large proportion of multiple myeloma patients relapse and require subsequent therapy and remissions become shorter as the disease progresses with each new line of therapy, teclistamab partially fulfills the need for more effective therapies. As an off-the-shelf product, teclistamab is at a significant competitive advantage over patient-specific CAR T-cell therapies; as such, a larger number of patients may be eligible to receive teclistamab versus CAR T-cell therapies. These include older patients who do not meet the current FDA criteria for CAR T-cell therapies and patients who rapidly progress and are unable to wait for CAR T-cell therapies to be manufactured.

What hurdles might it need to overcome to reach blockbuster status?

Although teclistamab has the advantage of being the first of its class to market, it will likely face stiff competition from other BCMA-targeted therapies (e.g., antibody-drug conjugates and CAR T-cell therapies) and bispecific therapies (including bispecifics targeted to BCMA). The latter will be teclistamab’s main hurdle. However, bispecific therapies, including teclistamab, are associated with infections, which could hamper uptake (and sales); heavily pretreated R/R multiple myeloma patients are at risk of infections owing to (often) low immunoglobin levels. Given there are several BCMA-targeted therapies marketed for multiple myeloma and others in the pipeline, significant questions remain about BCMA-targeted therapies, such as whether patients can be retreated with them and where they are best positioned in the treatment algorithm. Uncertainty over the optimal treatment sequences for some patients could prove to be a barrier to teclistamab’s uptake.

$1.8B

expected sales in 2027

67%

probability of success for teclistamab in Japan.

“The expression of BCMA is restricted to plasma cells, and it’s universally expressed in multiple myeloma. BCMA is definitely a great target for multiple myeloma. One way to exploit it is as antibody constructs, which typically have BCMA and CD3.”