Two Pivotal New Drugs Face FDA Advisory Committee Review in Mid-July

Jun 27, 2025 12:33 CST Updated 12:33

GSK

Pharmaceutical R&D Manufacturer

In mid-July, the FDA Advisory Committee in the United States will hold two crucial meetings consecutively, which will determine the fate of two blockbuster drugs——Belantamab Mafodotin and Brexpiprazole's fate is also a key "trial" that could reshape the treatment landscape.

These two drugs respectively represent important breakthroughs in the fields of hematological oncology and mental health, with the former beingMultiple MyelomaThe first ADC drug in the field, which is expected to become the first new PTSD treatment approved in over 20 years.

BCMA ADC Impacts Second-Line Treatment for Multiple Myeloma

On July 17, the FDA Oncology Drug Advisory Committee will discuss GSK's submitted Biologics License Application (BLA) for belantamab mafodotin, for use in combination with bortezomib and dexamethasone to treat patients with multiple myeloma (MM) who have received at least one prior therapy; and in combination with pomalidomide and dexamethasone for MM patients who have received at least one prior therapy, including lenalidomide.

Belantamab mafodotin is a first-in-class BCMA antibody-drug conjugate (ADC), composed of a humanized anti-BCMA monoclonal antibody and the cytotoxic agent auristatin F, linked together by a non-cleavable linker. The drug was initially developed by Seagen (which has been acquired by Pfizer). In December 2009, GSK entered into an agreement with Seagen to obtain the rights for the research, development, manufacturing, and commercialization of the drug.

In August 2020, based on the results of the Phase II DREAMM-2 study (primary endpoint: ORR), belantamab mafodotin received accelerated approval from the FDA and conditional approval from the EMA as a monotherapy for adult patients with relapsed or refractory MM who have received at least four prior therapies (including anti-CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents).

However, due to the confirmatory Phase III DREAMM-3 study evaluating belantamab mafodotin monotherapy versus pomalidomide plus low-dose dexamethasone (PomDex) in patients with relapsed or refractory MM who have received at least two prior therapies failing to meet the primary endpoint of PFS, GSK withdrew the drug’s approved indication in the United States in 2022 and in the European Union in 2023.GSK Initiates Withdrawal Process for BCMA ADC Drug）。

To explore the application potential of belantamab mafodotin as a second-line treatment for MM, GSK conducted two Phase III studies (DREAMM-7 and DREAMM-8). These two studies reached their primary endpoints in 2023 and 2024, respectively.

DREAMM-7 Study Evaluates Belantamab Mafodotin Plus Bortezomib and Dexamethasone (BorDex) vs. Johnson & Johnson’s CD38 Antibody Daratumumab Plus BorDex in Second-Line and Later Treatment for Relapsed or Refractory Multiple Myeloma

The DREAMM-8 study aims to evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (BPd) versus bortezomib in combination with pomalidomide and dexamethasone (PVd) as a second-line and later therapy for relapsed or refractory MM. After a median follow-up of 21.8 months, the median PFS in the BPd group was not reached, while it was 12.7 months in the PVd group, with an HR of 0.52. At 12 months, the PFS rate was 71% in the BPd group and 51% in the PVd group.

A Key Battle in the Field of PTSD

On July 18, the FDA Psychopharmacologic Drugs Advisory Committee (PDAC) will meet to discuss the supplemental New Drug Application (sNDA) for Rexulti (brexpiprazole tablets) in combination with sertraline for the treatment of adult patients with post-traumatic stress disorder (PTSD).

Brexpiprazole is a 5-HT1A receptor partial agonist, 5-HT2A receptor antagonist, and dopamine D2 receptor partial agonist developed by Otsuka Pharmaceutical. In November 2011, Lundbeck entered into an agreement with Otsuka Pharmaceutical worth up to $1.8 billion to obtain global co-development and commercialization rights for brexpiprazole. In July 2015, brexpiprazole was first approved in the United States for the treatment of major depressive disorder (MDD) or schizophrenia. In May 2023, the indications for brexpiprazole were further expanded to include agitation in Alzheimer's disease.

This sNDA is based on data from three randomized clinical trials (Trial 061, Trial 071, Trial 072). The primary endpoint of these three trials was the change in the Clinician-Administered PTSD Scale (CAPS-5) total score from randomization (Week 1) to Week 10 in patients diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Trial 061 is a Phase II clinical trial (n=321) that evaluated the efficacy and safety of brexpiprazole (1-3 mg/day, flexible dose) ± sertraline (100-200 mg/day) compared with sertraline monotherapy or placebo. The results showed that the total CAPS-5 score in the brexpiprazole + sertraline group significantly decreased (-16.4 points) compared to other groups, while the total CAPS-5 scores in the brexpiprazole monotherapy group, sertraline monotherapy group, and placebo group decreased by 12.2 points, 11.4 points, and 10.5 points, respectively.

Trial 071 is a Phase III clinical trial (n=416) that evaluated the efficacy and safety of brexpiprazole (2-3 mg/day, flexible dose) + sertraline (150 mg/day) compared with sertraline + placebo. The results showed that the total CAPS-5 score in the brexpiprazole + sertraline group significantly decreased compared to the sertraline + placebo group (-19.2 vs -13.6, LS mean difference: -5.59, P<0.001).

Trial 072 is a Phase III clinical trial (n=591) that evaluated the efficacy and safety of brexpiprazole (2-3mg/day, fixed dose) + sertraline (150mg/day) compared to sertraline monotherapy. The results showed that the study did not meet its primary endpoint, but the trend in reducing PTSD symptoms with brexpiprazole + sertraline (-18.3 points vs -17.6 points, P=0.66) was consistent with Trial 061 and Trial 071.

Three randomized trials showed that brexpiprazole + sertraline was generally well-tolerated in adult patients with PTSD, with no new safety observations identified. The safety and tolerability outcomes were consistent with the known profile of brexpiprazole for its approved indications and with findings observed in other clinical trials. Pooled analysis data indicated that the overall incidence of treatment-emergent adverse events (TEAEs) was 55.5% in the brexpiprazole + sertraline group and 56.2% in the sertraline + placebo group. Common TEAEs included nausea, headache, weight gain, and diarrhea.

PTSD is a mental health disorder that people who have experienced or witnessed traumatic events or situations are prone to, and it is one of the most common mental health disorders in the United States. Statistics show that there are approximately 13 million cases of PTSD in the U.S. each year, and about 6% of Americans will be diagnosed with PTSD at some point in their lives.

Currently, only sertraline and paroxetine have been approved for the treatment of PTSD. However, the efficacy rate of these drugs in treating PTSD is less than 60%, with complete remission rates below 20%-30%. Previously, another drug, MDMA (methylenedioxymethamphetamine), reached the stage of submission for marketing approval, but it faced strong opposition from PDAC and was ultimately rejected by the FDA.Both pivotal clinical trials met the primary endpoints, so why did the FDA still reject the approval for marketing?）。

If it can pass the PDAC test and gain FDA approval, Brexpiprazole + Sertraline will become the first FDA-approved PTSD treatment drug in over 20 years. This meeting will be a pivotal battle in the field of PTSD.

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