CHMP issues positive recommendation for six medicines including HSCT drug Zalmoxis

The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) published recommendations for the approval of six new medicines on 24 June 2016. In addition, the CHMP posted seven recommendations for the extension of therapeutic indications.

The full set of CHMP decisions are available to view here.

The recommendations include conditional marketing authorisation for the orphan-designated advanced therapy medicinal product (ATMP) Zalmoxis (MolMed, Italy), a cell-based therapy for the treatment of adult patients receiving a haploidentical haematopoietic stem cell transplant (HSCT). The cell-based therapy consists of donor lymphocytes designed to express a human herpes simplex thymidine kinase "suicide gene". The ATMP therapy has shown promising results in reducing the risk of graft-versus-host disease in which newly transplanted donor cells attack the transplant recipient's body. The CHMP issued the positive recommendation for Zalmoxis in conjunction with the EMA's Committee for Advanced Therapies (CAT), which assessed Zalmoxis as the first immune-gene therapy as a patient-specific adjunctive treatment in treating HSCT with high haematological malignancies. MolMed is targeting a patient population of about 1,300 high-risk haematological malignancies patients per year in the EU with haploidentical HSCT. In a statement the Italian firm noted the size of the patient population was increasing at a rate of about 30% annually. MolMed has also indicated that Zalmoxis could potentially offer a viable therapeutic solution to an estimated 11,000 EU patients with high-risk haematological malignancies who are candidates for allogeneic transplant and lack a fully compatible donor. On that basis, MolMed is confident of addressing a significant unmet clinical need for the life-threatening condition and potentially generating significant revenues for the in-house-developed gene therapy.

The CHMP approval of Zalmoxis was based on Phase I/II (TK007) and Phase III (TK008) clinical trials. Phase III trials investigating disease-free survival rates are ongoing. The study, involving 45 patients, showed Zalmoxis had a survival rate of 49% after one year of treatment. This compared with an inferred survival rate of 37% for 140 patients treated without the cell therapy. The market authorisation is conditional. Pending the publication of full clinical trial data, the EMA has said that it will "review the benefits and risks of Zalmoxis annually". Nevertheless, the recommendation is a positive development for the company and marks a turnaround from a 2014 decision by the US FDA to reject on the grounds that there was insufficient clinical trial data at the time. The Italian company is now likely to press ahead with the re-submission of a market authorisation application in the US, once the confirmatory clinical trial data is published (probably in late 2016 or 2017). The receipt of orphan medicine status will mean that the cell-based therapy benefits from a 10-year period of patent protection in the EU (subject to final clearance by the European Commission).

The CHMP also recommended granting market authorisation for Cinqaero (reslizumab; Teva, Israel) as an add-on maintenance therapy for the treatment of adult patients with severe eosinophilic asthma. The humanised interleukin 5 antagonist monoclonal antibody is indicated for patients inadequately controlled by high-dose inhaled corticosteroids plus another maintenance therapy.

Outlook and implications

The positive opinions published at the EMA's CHMP June meeting are likely to be formally adopted and approved by the European Commission within a two-month period. The upcoming European Commission decision will grant commercialisation throughout all 28 EU countries (as well as Iceland, Liechtenstein, and Norway). The highlight of the most recent set of CHMP recommendations is certainly the HSCT therapy Zalmoxis. MolMed is well placed to command a high price for the cell-based therapy, which has to be tailored to treat each patient. There is a reasonable likelihood that the innovative therapy will receive favourable reimbursement decisions following applications for approval at national level starting in the second half of 2016. MolMed has given no public nor clear indication of the price tag for Zalmoxis at this stage. A 2016 study published by the medical journal Bone Marrow Transportation recently reported that a record number of 40,?829 HSCTs in 36,469 patients across 47 countries were recorded in 2014, suggesting significant growth in transplant activity in East European countries. The main indications for HSCT were reported as being leukaemias (11,853 or 33%), lymphoid neoplasias (20,802 or 57%), solid tumours (1458 or 4%), and non-malignant disorders (2,203 or 6%).