On February 25, 2016 AstraZeneca and Acerta Pharma BV, a company in which AstraZeneca has a majority equity investment, reported 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 (Filing, 6-K, AstraZeneca, FEB 25, 2016, View Source [SID:1234509193]). 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.i,ii Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment. iii SLL is a clinically similar disease localized to the lymph nodes.iv
MCL is an aggressive non-Hodgkin’s lymphoma (NHL) typically associated with very poor outcomes.v MCL represents around 5% of all NHLs.vi The name comes from the fact that the tumour cells originate in the mantle zone of the lymph node. vi
WG is a rare, slow-growing cancer predominantly affecting older individuals, with a mean age of 60 at diagnosis.vii, viii and median survival from five to nearly eleven years. vii, viii
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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 WG, 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.
i Chronic Lymphocytic Leukemia. Leukemia & Lymphoma Society Website. View Source Accessed February 19, 2016.
ii What are the key statistics for chronic lymphocytic leukemia? American Cancer Society Website. View Source . Accessed February 19, 2015.
iii Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic lymphocytic leukemia. Cancer Control. 2012; 19(1):37-53.
iv Chronic lymphocytic leukemia/Small lymphocytic lymphoma, National Cancer Institute Website. View Source Accessed February 19, 2016.
v Campo E and Rule S. Mantle cell lymphoma: evolving management strategies. Blood. 2015 Jan 1;125(1):48-55.
vi Mantle Cell Lymphoma, Lymphoma.org Website. View Source;b=6300157 Accessed February 19, 2016.
vi Lymphoplasmacytic lymphoma. National Cancer Institute. Surveillance, Epidemiology, and End Results program. View Source Accessed February 19, 2016.
vii Dimopoulos MA, Kastritis E, Ghobrial IM. Waldenström’s macroglobulinemia: a clinical perspective in the era of novel therapeutics. Ann Oncol. 2016 Feb;27(2):233-40.
viii Oza and Rajkumar. Waldenstrom macroglobulinemia: prognosis and management. Blood Cancer Journal (2015) 5, e394; doi:10.1038/bcj.2015.28
ix European Medicines Agency web site. "Orphan Designation." View Source;mid=WC0b01ac05800240ce. Accessed February 17, 2016.
About Acalabrutinib
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.