AstraZeneca and Acerta Pharma BV, a company in which AstraZeneca has a majority equity investment, announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) adopted three positive opinions recommending acalabrutinib (ACP-196) for designation as an orphan medicinal product. The three positive opinions are for the treatment of chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (Waldenström’s macroglobulinaemia, MG).

Sean Bohen, executive vice-president of global medicines development and chief medical officer at AstraZeneca, said, “Today’s three positive opinions recommending acalabrutinib for designation as an orphan medicinal product are important milestones. They reinforce the strategic rationale for our investment in Acerta, demonstrating clear progress in developing a potential best-in-class medicine that could transform treatment for patients across a range of blood cancers. The positive opinions underscore the continued need for the development of new therapies in these serious and life-threatening conditions and support our commitment to bring new medicines to patients as quickly as possible.”

CLL is a slow-growing blood and bone marrow cancer that accounts for approximately one in four cases of leukaemia. Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment. SLL is a clinically similar disease localized to the lymph nodes.

MCL is an aggressive non-Hodgkin’s lymphoma (NHL) typically associated with very poor outcomes.v MCL represents around 5 per cent of all NHLs. The name comes from the fact that the tumour cells originate in the mantle zone of the lymph node.

WM is a rare, slow-growing cancer predominantly affecting older individuals, with a mean age of 60 at diagnosis.and median survival from five to nearly eleven years.

The COMP adopts an opinion on Orphan Drug Designation, after which the opinion is submitted to the European Commission (EC) for endorsement. Orphan Drug Designation is a status assigned to a medicine intended for use in rare diseases.ix To be granted orphan status by the EC, a medicine must be intended for the treatment, prevention or diagnosis of a disease that is life threatening and has a prevalence of up to five in 10,000 in the European Union. Additionally, the intended medicine must aim to provide significant benefit to those affected by the condition. Orphan status provides companies with development and market exclusivity incentives for designated compounds and medicines.

In addition to ongoing phase II/III trials in CLL, MCL and WM, acalabrutinib is currently being tested in phase I/II trials in monotherapy as well as in combination with immunotherapy or chemotherapies in a range of other blood cancers and solid tumours.

Acalabrutinib is a highly selective, irreversible, second generation BTK inhibitor, with approximately 1,000 patients treated to date in clinical studies across the entire development programme. More than 600 patients have been treated with acalabrutinib monotherapy. Phase I/II data showing a favourable safety profile and efficacy in relapsed/refractory chronic lymphocytic leukaemia patients was presented at the American Society of Haematology Annual Meeting & Exposition in December 2015, with simultaneous publication in the New England Journal of Medicine.

Potentially registrational studies in haematological malignancies are ongoing. In addition, a head-to-head study versus ibrutinib in high risk chronic lymphocytic leukaemia patients is currently ongoing.

Acalabrutinib is also currently being tested in multiple phase I/II studies in solid tumours, as monotherapy or in combination with immune checkpoint inhibitors or other standard of care regimens.