European Medicines Agency Recommends Granting a Marketing Authorisation for Dinutiximab

It is considered for the treatment of high-risk neuroblastoma in children

On 21 May 2015, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product dinutiximab (Unituxin) for the treatment of high-risk neuroblastoma in children. Unituxin was designated an orphan medicinal product on 21 June 2011.

The applicant for this medicinal product is United Therapeutics Europe Ltd.

Unituxin will be available as 3.5 mg/ml concentrate for solution for infusion. The active substance of Unituxin is dinutuximab, a monoclonal chimeric antibody (ATC code: L01XC16) which reacts specifically with the ganglioside GD2. GD2 is highly expressed on the surface of neuroblastoma cells but only minimally expressed on the surface of normal human neurons, peripheral pain fibres, and skin melanocytes.

The safety and efficacy of Unituxin were evaluated in a clinical trial in children with high-risk neuroblastoma who had already responded to chemotherapy (at least a partial response) and were further treated with myeloablative therapy and autologous stem-cell transplantation.

The study randomly assigned 230 patients to receive Unituxin combined with other immunotherapy (GM-CSF and IL-2) and an oral retinoid medicine (isotretinoin) or isotretinoin alone. The benefits with Unituxin are an improvement in the 2-year estimates of event free survival and the 3-year estimates of overall survival. After two years, 66% of patients receiving the Unituxin combination were alive and free from recurrence or tumour growth, while this was the case in only 48% of patients treated with isotretinoin alone during the same time period. 

The most common side effects are pain, allergic reactions and hypotension.

Because GD2 is also present on normal nerve cells, Unituxin causes irritation and severe pain of the nerve cells. It is therefore recommended that pain relief is given before and during treatment with Unituxin. Despite prophylaxis, two thirds of children experience pain and about 40% experience severe pain.

The CHMP recommended that the safety profile of Unituxin be further assessed post-authorisation and required the company to include this in their risk management plan for Unituxin.

The full indication is: "Unituxin is indicated for the treatment of high-risk neuroblastoma in patients aged 12 months to 17 years, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and autologous stem cell transplantation (ASCT). It is administered in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin."

Unituxin should be prescribed by physicians experienced in the treatment of cancer.

Because neuroblastoma is rare, Unituxin received an orphan designation from the Committee for Orphan Medicinal Products (COMP) in 2011. Orphan designation and the associated incentives such as fee reductions for scientific advice are among the European Medicines Agency’s most important instruments to encourage the development of medicines for patients with rare diseases.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

The opinion adopted by the CHMP at its May 2015 meeting is an intermediary step on Unituxin’s path to patient access. The CHMP 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, each Member State will take a decision on price and reimbursement based on the potential role/use of this medicine in the context of its national health system.