Date: 2017-10-31
Type of information: Granting of a Market Authorisation in the US
Product name: Calquence®
Compound: acalabrutinib - (S)-4-(8-amino-3-(1-but-2-ynoylpyrrolidin-2-yl)-imidazo[1,5-a]pyrazine-1-yl)-N-(pyridine-2-yl)-benzamide
Therapeutic area: Cancer - Oncology - Rare diseases
Action mechanism:
- kinase inhibitor/Bruton's tyrosine kinase inhibitor. Acalabrutinib (ACP-196) is a potential best-in-class irreversible oral Bruton's tyrosine kinase (BTK) inhibitor, currently in Phase III development for B-cell blood cancers and in Phase I/II clinical trials in multiple solid tumours.
Company: Acerta Pharma (USA - CA, The Netherlands), now AstraZeneca (UK)
Disease: mantle cell lymphoma
Latest news:
- • On October 31, 2017, the FDA has granted accelerated approval to Calquence® (acalabrutinib) for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy. Calquence® was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Calquence® and the sponsor is currently conducting this trial.
- The approval was based on data from a single-arm trial that included 124 patients with mantle cell lymphoma who had received at least one prior treatment. The trial measured how many patients experienced complete or partial shrinkage of their tumors after treatment (overall response rate). In the trial, 81 percent of patients had a complete or partial response (40 percent complete response, 41 percent partial response).
Common side effects of Calquence® include headache; diarrhea; bruising; fatigue and muscle pain (myalgia); and reduced levels of red blood cells (anemia), platelets (thrombocytopenia) and neutrophils (neutropenia) in the blood. Serious side effects include bleeding (hemorrhage), infections and irregular heartbeat (atrial fibrillation). Additional cancers, known as second primary malignancies, have occurred in some patients taking Calquence®. Women who are breastfeeding should not take Calquence® because it may cause harm to a newborn baby.
The FDA granted this application Priority Review and Breakthrough Therapy designations.
- • On August 2, 2017, AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, announced that the FDA has accepted and granted Priority Review for the New Drug Application (NDA) for acalabrutinib. The Prescription Drug User Fee Act (PDUFA) date is during the first quarter of 2018.
- The NDA is based on results from the Phase II ACE-LY-004 clinical trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory mantle cell lymphoma who have received at least one prior therapy. Results from this trial will be submitted for presentation at a forthcoming medical meeting. The acalabrutinib development programme includes both monotherapy and combination therapy strategies in a broad range of blood cancers and solid tumours. The programme includes the Phase III ACE-LY-308 clinical trial evaluating acalabrutinib as a 1st-line treatment for patients with mantle cell lymphoma.
• On August 1st, 2017, AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, announced that the FDA has granted Breakthrough Therapy Designation for acalabrutinib for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. The FDA granted Breakthrough Therapy Designation based on the totality of clinical data from the acalabrutinib development programme, including data from the Phase II ACE-LY-004 clinical trial in patients with relapsed or refractory MCL.
- This is the fifth Breakthrough Therapy Designation that AstraZeneca has received from the FDA for an oncology medicine since 2014 and the first for the company in haematology.
- • On February 25, 2016, the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for acalabrutinib for treatment of mantle cell lymphoma.
- • On September 21, 2015, the FDA has granted orphan drug designation for (S)-4-(8-amino-3-(1-but-2-ynoylpyrrolidin-2-yl)-imidazo[1,5-a]pyrazine-1-yl)-N-(pyridine-2-yl)-benzamide for the treatment of mantle cell lymphoma.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-10-31
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2015-09-21
Orphan status UE: 2016-03-21
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
