EMA’s human medicines committee (CHMP) has recommended a conditional marketing authorisation in the European Union (EU) for Elrexfio (elranatamab) as a monotherapy (used on its own) for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies and whose cancer has worsened since they received their last treatment.
Multiple myeloma is a rare cancer of the plasma cells, a type of white blood cell that produces antibodies and is found in the bone marrow. In multiple myeloma, the proliferation of plasma cells is out of control, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. 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 patient survival. However, new medicines are needed for patients who have already been treated with the three main classes of medicines (immunomodulatory agents, proteasome inhibitors and monoclonal antibodies) and who no longer respond to them.
Elranatamab, the active substance in Elrexfio, is a monoclonal antibody that targets two proteins simultaneously. By attaching at the same time to a protein called B-cell maturation antigen (BCMA), which is present on the surface of the multiple myeloma cells, and to CD3, a protein that is present on the T cells (cells in the immune system), the medicine activates the T cells to kill the multiple myeloma cells.
Elrexfio was supported through EMA’s PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients’ unmet medical needs.
The CHMP based its recommendation for a conditional marketing authorisation on an open-label, single arm, multicentre, phase 2 clinical trial. The part of trial that was considered as pivotal investigated the efficacy of Elrexfio monotherapy in 123 participants with refractory multiple myeloma who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, but who had not received prior BCMA-directed therapy. 61% of patients enrolled in the trial responded to the treatment with Elrexfio and more than 70% of the responding patients have a probability to live without their disease getting worse for an average of 15 months.
The overall safety profile of elranatamab was established by analysing data from 265 participants. The most common side effects are a decrease in blood cells, infections and cytokine release syndrome (CRS) (i.e. a condition causing fever, vomiting, shortness of breath, headache and low blood pressure). One of the main risks associated with elranatamab use is neurological toxicity including immune effector cell-associated neurotoxicity (ICANS), as these events have the potential to be life-threatening or fatal if not properly managed. Monitoring and mitigation strategies for CRS and ICANS are described in the product information and in the risk management plan that is an integral part of the authorisation.
Elrexfio 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 confirm the results obtained from the pivotal trial, the company will have to submit data from a randomised phase 3 trial comparing the efficacy and safety of elranatamab monotherapy and elranatamab used in combination with daratumumab versus the treatment regimen daratumumab, pomalidomide, and dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, but not more than three, including lenalidomide and a proteasome inhibitor. The company is also required to submit the final results of the pivotal phase 2 clinical trial.
The opinion adopted by the CHMP is an intermediary step on Elrexfio’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 or use of this medicine in the context of the national health system of that country.
Notes
- The applicant for Elrexfio is Pfizer Europe MA EEIG.
- Elrexfio was designated as an orphan medicinal product on 19 July 2021.
- Elrexfio was accepted into the PRIME scheme on 26 March 2021.
- Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.
Source/Attributions: This news post was originally posted at www.ema.europa.eu