Cancer may be passed down to the next generation through the genetic inheritance and those who firstly decipher the gene code are getting ahead in anticancer drug development. US FDA granted accelerated approval to Keytruda, a treatment for patients whose cancer have specific genetic feature (biomarker) in 23 May. This is the first time FDA has approved a cancer treatment based on common biomarker rather than the location in the body where the tumor originated. It opened a new page of drug development in cancer treatment and more and more drugs designed by targeting the common biomarker instead of single indication are highly likely to be approved following Keytruda’s approval pathway.
Both CX-5461 and Merck’s Keytruda have been selected as “Dream Team Drug” by SU2C (Stand Up to Cancer), an international renowned anticancer nonprofit organization and supported by their research funding. The core technology of research and development of these two drugs is based on specific genetic feature or biomarker of tumors. Keytruda is for solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). CX-5461 is designed for cancer patients with BRCA or HR deficiency or mutations. SU2C has so far selected 22 Dream Teams with a total research funding of more than US$ 300 million, and quite a few drugs have been granted breakthrough approval to the market.
CX-5461 is designed to stabilize DNA G-quadruplexes of cancer cell and lead to replication fork stalling. While acting in concert with HR pathway deficiency, such as BRCA1/2 mutations, which stalls replication forks undergo DNA breaks and causes cancer cell death. CX-5461 in combination with HRD tumors may be exploited through a synthetic lethality approach targeting DNA repair defects in HRD tumors. CX-5461 is first in class small molecule drug and also the first new drug applying G-quadruplexes mechanism in clinical stage. It has the potential to treat multiple indications including breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, etc.
To expedite the review of new drug to treat serious conditions and fill the unmet medical needs, FDA offers four approval mechanisms including Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review. Senhwa plans to file IND in US and hopes that CX-5461 will be granted accelerated approval for its novelty and potential to save lives across the globe.