First BRCA Targeted Drug Shows Early Promise, BioMarin Jumping to Phase III Trials
BRCA genes have been a hot topic, from patent hearings before the Supreme Court to Angelina Jolie's recent double mastectomy. The detection of mutations in the BRCA1 and BRCA2 genes can give patients and their doctors a means of deciphering the chance of developing breast or ovarian cancer. Close to 60 percent of women with a certain BRCA1 mutation will develop breast cancer and around 50 percent will develop ovarian cancer. Yet, there are currently no pharmaceutical treatments that target these well-documented mutations and the cascades into cancer they initiate.
BioMarin, a pharmaceutical company that focuses on drugs for rare diseases, has developed a drug, BMN673, that has shown promise in early-stage Phase I/II clinical trials for targeting the BRCA pathway of cancer development. The study took place in 70 patients with advanced or reoccurring solid tumors. The data from the study showed that 11 out of 25 patients with ovarian cancer saw tumor shrinkage by at least 30 percent. In 18 breast cancer patients, seven saw their tumors shrink and 12 showed signs of clinical benefit. One patient's breast cancer even completely disappeared.
"Patients with germline BRCA-associated tumors have no targeted treatment options. There is a need for therapies that target specific molecular defects in tumors, and PARP inhibitors offer that potential in BRCA-related cancers. We have seen excellent anti-tumor activity in some of our patients treated with BMN 673. Continued study of this molecule will be meaningful for advancing the care for patients suffering from these cancers," said Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London.
Although the aim of the Phase I/II trial was to evaluate the maximum tolerated dose (MTD) and the secondary aim was to evaluate safety and preliminary effects of the drug, the positive clinical results are pushing the company to pursue Phase III clinical trials. "We are encouraged by this early stage data on BMN 673, including the safety profile, and substantial anti-tumor activity. We look forward to initiating a Phase 3 trial in metastatic gBRCA breast cancer patients to pursue a safe and effective therapy in a once-daily, oral dose that meets an unmet medical need in this aggressive form of cancer," said Dr. Hank Fuchs, M.D., Chief Medical Officer of BioMarin.
BRCA1 and BRCA2 genes are DNA repair genes that work to fix issues with DNA. When the repair genes themselves are damaged, they cannot help fix DNA damage, increasing risks of developing cancer. The new drug, BMN 673, targets poly ADP ribose polymerase (PARP), an enzyme that also helps repair DNA and is used by cancer cells to survive and repair their DNA. By blocking this other DNA repair enzyme, researchers hope that cancers cells would be less able to repair their DNA after damage and would ultimately self-destruct.
The drug is currently under investigation for BRCA-related cancers such as ovarian cancer, Ewing's sarcoma, small cell lung carcinoma, prostate cancer, and pancreatic cancer.
The presentation of the BioMarin ASCO presentation can be found here.