EMA’s human medicines committee (CHMP) has recommended granting a conditional marketing authorisation in the European Union for Blenrep (belantamab mafodotin) to treat adult patients with relapsed and refractory multiple myeloma who no longer respond to treatment with an immunomodulatory agent, a proteasome inhibitor and a CD-38 monoclonal antibody.
Multiple myeloma is a cancer of a type of white blood cell called plasma cells that is responsible for about 2% of all cancer deaths. Normal plasma cells are found in the bone marrow and are an important part of the immune system. Plasma cells make the antibodies that enable the body to recognise and attack germs such as viruses or bacteria. They originate from B-cell lymphocytes and form when B-cells respond to an infection. When plasma cells become cancerous, they no longer protect the body from infections and produce abnormal proteins that can cause problems affecting the kidneys, bones or blood.
A range of new medicines for the treatment of multiple myeloma have been developed and approved in recent years, leading to a steady overall improvement in survival of patients. However, for patients who have already been treated with three major classes of drugs (immunomodulatory agents, proteasome inhibitors and monoclonal antibodies) and no longer respond to these drugs, the outlook is still bleak. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed three months or less.
Blenrep was accepted in EMA’s PRIME scheme and has benefited from the extra support offered by the Agency to medicines that have a particular potential to address patients’ unmet medical needs. Blenrep has a new mechanism of action that targets B-cell maturation antigen (BCMA), a protein that is present on the surface of virtually all multiple myeloma cells. BCMA is absent from normal B-cells, making it an ideal drug target.
Structurally, Blenrep is an antibody-drug conjugate that combines a monoclonal antibody with maleimidocaproyl monomethyl auristatin F (mcMMAF), which is a cytotoxic agent. The medicine binds to BCMA on myeloma cell surfaces and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the ‘programmed’ death of the cancerous plasma cells.
The main study on which the CHMP’s recommendation for a conditional marketing authorisation is based was a phase 2, open label, randomised, two-arm study. The study investigated the efficacy and safety of two doses of belantamab mafodotin in multiple myeloma patients whose disease was still active after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs and proteasome inhibitors and who didn’t respond to treatment with an anti-CD38 monoclonal antibody. The most common side effects found in participants in clinical trials with Blenrep were keratopathy (a disease affecting the cornea, the transparent layer in front of the eye that covers the pupil and iris) and thrombocytopenia (a condition that causes low blood platelet counts, which can lead to bleeding and bruising). With regard to the corneal risks associated with belantamab mafodotin, patients would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed.
Blenrep is recommended for a conditional marketing authorisation, one of the EU regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.
In order to better characterise the effectiveness and safety of the medicine, the company will have to submit the results of a randomised confirmatory (phase 3) trial comparing Blenrep with pomalidomide plus low-dose dexamethasone, which is a standard treatment option for relapsed and refractory multiple myeloma. The company is also required to submit the final results of the pivotal phase 2 study.
As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorised across the EU. Further efficacy and safety data will be collected through on-going studies and post-marketing reports and will be regularly reviewed by the CHMP and EMA’s safety committee (PRAC).
The opinion adopted by the CHMP is an intermediary step on Blenrep’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.