Clovis Oncology will partner on a companion diagnostic for its approved drug Rubraca® (rucaparib) with Myriad Genetics to fulfill a post-approval regulatory commitment related to the ovarian cancer treatment, the companies said today.
Myriad will apply its BRACAnalysis CDx® test under the collaboration, whose value and other financial terms were not disclosed.
Rubraca is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy to treat patients with deleterious BRCA mutation- (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.
Clovis has acknowledged that continued approval of Rubraca under that indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
On December 19, 2016, Rubraca became the second PARP inhibitor to win FDA approval. Also approved by the FDA that day was a companion diagnostic for Rubraca—Foundation Medicine’s FoundationFocus™ CDxBRCA test, the first next-generation sequencing (NGS)-based companion diagnostic approved by the agency. The NGS test is designed to detect the presence of deleterious BRCA gene mutations in the tumor tissue of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for treatment with Rubraca.
Myriad and Clovis noted in a statement that the FoundationFocus CDxBRCA test does not discriminate between germline and somatic mutations. Foundation Medicine acknowledges that the tumor BRCA1 and BRCA2 mutations detectable through its tissue-based genomic assay “may include both germline (inherited) and somatic (acquired)” mutations.
“This partnership with Myriad Genetics not only enables us to fulfill our post-marketing commitment to the FDA, but will enhance the companion diagnostic information already available to physicians and patients, providing a robust toolkit for personalizing treatment of patients with BRCA1/2 mutations,” stated Patrick J. Mahaffy, president and CEO, Clovis Oncology.
Rubraca was approved under the FDA’s accelerated approval program based on results from two multicenter, single-arm, open-label clinical trials involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with two or more chemotherapy regimens.
The trials measured the percentage of participants who experienced complete or partial shrinkage of their tumors (overall response rate). Fifty-four percent of the participants who received Rubraca in the trials experienced complete or partial shrinkage of their tumors lasting a median of 9.2 months. BRCA gene mutations were confirmed in 96% of tested trial participants with available tumor tissue using the FoundationFocus CDxBRCA test.
Since 2014, BRACAnalysis CDx has been an approved companion diagnostic for the first PARP inhibitor to win FDA approval, AstraZeneca’s Lynparza® (olaparib). Myriad has agreed to submit a supplementary premarket approval (sPMA) application under its existing PMA for BRACAnalysis CDx to include Rubraca.
BRACAnalysis CDx is intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. According to Myriad, results of the test are used in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants, who are or may become eligible for treatment with Lynparza.
“BRACAnalysis CDx is the only germline companion diagnostic test approved by the FDA to identify patients with BRCA1/2 mutations, and we are excited to support Clovis’ clinical development program and help identify patients who are most likely to benefit from rucaparib,” Myriad president and CEO Mark C. Capone said in a statement.