GlaxoSmithKline’s Blood Cancer Drug Reenters U.S. Market with Limited FDA Approval Scope

News">

Blenrep Receives FDA Green Light for Multiple Myeloma, But With New Restrictions

Washington, D.C. – After a three-year absence from the market, GlaxoSmithKline’s (GSK) Blenrep (belantamab mafodotin-blmf) has secured renewed approval from the U.S. Food and Drug Governance (FDA) for the treatment of relapsed or refractory multiple myeloma. However, the approval isn’t as broad as GSK initially anticipated, focusing on specific drug combinations and later lines of treatment.

the Journey of Blenrep: From Promise to Pause and Return

Blenrep, an antibody-drug conjugate (ADC) designed to target BCMA – a protein found on the surface of cancerous plasma cells – first received accelerated approval in 2020 as a fifth-line monotherapy for multiple myeloma.This initial approval was followed by setbacks when a Phase 3 confirmatory trial failed to meet expectations, leading GSK to withdraw the drug globally in 2022. Despite this, clinical trials continued, paving the way for the current resubmission.

New Clinical Data Drives Re-approval

The FDA’s decision to re-approve Blenrep is based on data from two pivotal Phase 3 studies. One study investigated the combination of Blenrep with Takeda Pharmaceutical’s Velcade, while the othre examined its use alongside Bristol Myers Squibb’s Pomalyst. Both regimens were administered in conjunction with dexamethasone,a common corticosteroid used in cancer treatment. These studies demonstrated statistically significant and clinically meaningful improvements in progression-free survival.

Limited Approval and Market Landscape

The current FDA approval restricts Blenrep’s use to combination therapy with velcade, specifically for patients who have undergone at least three prior lines of treatment. This is narrower than the recent European Union approval, which allows for combinations with both Velcade and Pomalyst as early as second-line treatment. The FDA’s decision was informed by data from 217 patients receiving the Blenrep-Velcade combination as a third-line treatment. This cohort experienced a median progression-free survival of 31.3 months,a considerable advancement over the 10.4 months observed in the comparator group.Overall survival data also showed a benefit, with the Blenrep arm not yet reaching median survival compared to the comparator’s 35.7 months.

Ocular Toxicity Remains a Key Concern

A known side effect associated with ADCs, including Blenrep, is ocular toxicity. Eye-related adverse events, including blurred vision and vision loss, were prominent in the clinical trials, with 92% of patients experiencing some form of ocular toxicity. Grade 3 or 4 severity cases were observed in 83% of patients, requiring dose modifications in many instances. This risk has led to a black box warning on the drug’s label. In May, an FDA advisory committee even voted against the drug’s benefit/risk profile in the context of second-line treatment, partially due to the potential for eye-related complications and limited U.S. patient representation in the trials.

enhanced REMS Program for Patient Safety

To mitigate the risk of ocular toxicity, the FDA requires a Risk Evaluation and mitigation Strategy (REMS) for Blenrep. GSK’s new REMS program incorporates optometrists and ophthalmologists, establishing a streamlined and digitized process for clinicians to report and manage potential eye complications. The digitized system will allow for data input via mobile devices, reducing administrative burdens.

Multiple Myeloma Treatment Landscape and Market Potential

Multiple myeloma, impacting approximately 34,250 Americans in 2024 according to the American cancer Society, remains a significant health challenge. The market for multiple myeloma therapies is projected to reach $45 billion by 2032, driven by the frequent relapse observed in patients and the need for alternative treatment options. Existing therapies like Abecma (Bristol myers Squibb) and Carvykti (Johnson & Johnson/Legend Biotech) – BCMA-targeting CAR T-cell therapies – and Tecvayli (Johnson & Johnson) have already altered the treatment paradigm. blenrep’s unique administration method – a 30-minute infusion every three weeks in a community hospital setting – offers a practical advantage, as over 70% of U.S. patients are treated in community hospitals.

Therapy	Target	Approval Line
Blenrep (belantamab mafodotin-blmf)	BCMA	3rd-line (with Velcade)
Carvykti (ciltacabtagene autoleucel)	BCMA	2nd-line
Abecma (idecabtagene vicleucel)	BCMA	3rd-line
Tecvayli (teclistamab-cqyv)	BCMA	5th-line

GSK anticipates peak sales of approximately £3 billion ($3.8 billion) for Blenrep, although these projections were initially based on a second-line approval. Ongoing clinical trials are aimed at expanding Blenrep’s indications, including evaluation in earlier treatment settings, with the plan to include greater U.S.patient representation.

“Working closely with the FDA, our clinical progress and evidence generation plans continue to explore the use of Blenrep in earlier and all stages of multiple myeloma globally, with additional data expected in 2028,” said GSK Chief Scientific Officer Tony Wood.

Understanding Multiple Myeloma: Multiple myeloma occurs when plasma cells, a type of white blood cell responsible for producing antibodies, become cancerous.These cancerous cells accumulate in the bone marrow, interfering with the production of healthy blood cells. Common symptoms include bone pain, fatigue, and frequent infections.

The Role of BCMA: BCMA (B-cell maturation antigen) is a protein highly expressed on multiple myeloma cells.Targeting BCMA has emerged as a promising therapeutic strategy,with several approved therapies utilizing this target.

Antibody-Drug Conjugates (adcs): ADCs consist of an antibody linked to a potent cytotoxic drug. The antibody selectively binds to cancer cells, delivering the drug directly to the tumor, minimizing damage to healthy tissues.

What questions do you have about the re-approval of Blenrep and its impact on multiple myeloma treatment? How will this approval shape future research and development in the field of blood cancer therapies?

Image courtesy of GSK

What are the implications of the FDA’s conditional approval of Blenrep for patients who have not received four or more prior lines of therapy?

Blenrep’s Conditional return: Understanding the FDA’s Decision

GlaxoSmithKline (GSK) has seen its multiple myeloma drug, Blenrep (belantamab mafodotin-blmf), reintroduced to the U.S. market, but with a substantially narrowed FDA approval. This comes after a voluntary withdrawal in late 2022 following results from the DREAMM-3 trial which failed to meet pre-specified efficacy criteria. The re-approval, granted in October 2025, is specifically for patients who have received at least four prior lines of therapy. This limited scope reflects a cautious approach by the FDA, acknowledging the drug’s potential benefit in a heavily pre-treated population while addressing safety concerns.

This re-entry impacts multiple myeloma treatment, blood cancer therapies, and the broader oncology drug market. Patients and healthcare providers are carefully evaluating the implications of this conditional approval.

The DREAMM-3 Trial and Subsequent Withdrawal

The initial approval of blenrep in 2020 was based on promising results from the DREAMM-2 trial, demonstrating significant response rates in patients with relapsed or refractory multiple myeloma.However, the subsequent DREAMM-3 trial, designed to confirm these benefits, showed a lack of statistically significant improvement in progression-free survival compared to standard-of-care regimens.

Key findings from DREAMM-3 that led to the withdrawal included:

* Lack of PFS Improvement: The primary endpoint of progression-free survival was not met.

* Ocular Toxicity: A concerning rate of ocular toxicities,including corneal endothelial cell loss,continued to be observed.This side effect can lead to vision impairment.

* Safety Profile Concerns: the risk-benefit profile prompted GSK to voluntarily withdraw the drug from the U.S. market.

FDA’s Revised Approval: A Targeted Approach

The FDA’s decision to re-approve Blenrep, albeit with limitations, centers around data suggesting a benefit for patients with limited treatment options. The new approval specifically targets individuals who have already undergone four or more prior lines of therapy for multiple myeloma. This population often has exhausted standard treatments and may benefit from a drug like Blenrep, even with its associated risks.

Hear’s a breakdown of the revised approval criteria:

1. Prior Lines of Therapy: Patients must have received at least four prior lines of therapy.
2. Relapsed or Refractory Disease: The multiple myeloma must be relapsed or refractory to prior treatment.
3. Ophthalmological monitoring: Strict ophthalmological monitoring is required throughout treatment to manage potential ocular toxicities.
4. Risk Evaluation and Mitigation Strategy (REMS): The FDA has mandated a REMS program to ensure appropriate patient selection and monitoring.

Understanding Belantamab Mafodotin’s Mechanism of Action

Blenrep is a first-in-class antibody-drug conjugate (ADC). It targets BCMA (B-cell maturation antigen), a protein highly expressed on multiple myeloma cells. The antibody delivers a cytotoxic agent directly to the cancer cells, aiming to kill them while minimizing damage to healthy tissues.

* Targeted Therapy: BCMA is almost exclusively found on myeloma cells, making it an attractive target.

* ADC Technology: The drug combines the specificity of an antibody with the potency of a chemotherapy drug.

* Cytotoxic Payload: The drug delivers a potent toxin directly into the myeloma cells.

Managing Ocular Toxicity: A Critical Component of Treatment

Ocular toxicity remains a significant concern with Blenrep. The FDA’s re-approval is contingent on rigorous monitoring and management of this side effect.

Key strategies for managing ocular toxicity include:

* Baseline and Regular Eye Exams: Thorough ophthalmological examinations are required before starting treatment and regularly throughout the treatment course.

* Corneal Endothelial Cell (CEC) Monitoring: CEC counts are closely monitored, as a decrease in these cells is indicative of potential toxicity.

* Dose Modifications and Treatment Interruptions: Dose adjustments or temporary interruptions might potentially be necessary based on CEC counts and the growth of ocular symptoms.

* Patient Education: Patients must be educated about the signs and symptoms of ocular toxicity and instructed to report any vision changes immediately.

Impact on Multiple Myeloma treatment Landscape

The reintroduction of Blenrep, even with limited approval, adds another option to the treatment arsenal for multiple myeloma. however, its role will likely be reserved for later lines of therapy when other options have been exhausted.

Other treatment options for multiple myeloma include:

* Proteasome Inhibitors: Bortezomib, carfilzomib, ixazomib

* Immunomodulatory Drugs (IMiDs): Lenalidomide, pomalidomide

* Monoclonal antibodies: Daratumumab, isatuximab

* CAR-T Cell Therapy: Ide-cel, cilta-cel

* Stem Cell Transplant: Autologous and allogeneic transplant options.

Real-World Evidence and Future Research

Ongoing real-world evidence collection will be crucial to further define Blen