The company added an indication to Lynparza’s label for the treatment of adults with metastatic castration-resistant prostate cancer, while cutting an antibody for Crohn’s disease and ulcerative colitis.
Pictured: AstraZeneca sign on building/Courtesy of Jonathan Weiss/Shutterstock
Thursday, the FDA approved AstraZeneca and Merck’s Lynparza (olaparib) for the treatment of adults with metastatic castration-resistant prostate cancer when used in combination with abiraterone and prednisone or prednisolone.
AstraZeneca also announced it was terminating the inflammatory bowel disease (IBD) development program for brazikumab, an anti-IL-23 monoclonal antibody being trialed for Crohn’s disease (CD) and ulcerative colitis (UC).
Lynparza Wins Eighth Indication
Lynparza’s new indication covers metastatic castration-resistant prostate cancer (mCRPC) patients with known or suspected deleterious BRCA mutations. The approval is based on a subgroup analysis of the Phase III PROpel study, which showed that the Lynparza regimen induced “highly clinically meaningful improvements” in radiographic progression-free survival and overall survival, as compared with abiraterone alone.
As for safety, Lynparza’s adverse effects were in line with what had been reported in previous trials.
Thursday’s approval adds an eighth indication for Lynparza. The oral PARP inhibitor was first approved in December 2014 as a monotherapy for patients with germline BRCA-mutated advanced ovarian cancer who had undergone at least three prior lines of chemotherapy.
In September 2022, AstraZeneca pulled this indication following a subgroup analysis of the Phase III SOLO3 trial, which found that the drug could increase the risk of death by 33% relative to standard chemotherapy.
Lynparza remains on the market for the maintenance treatment of ovarian cancer, as well as for various indications in breast, pancreatic and prostate cancers.
IBD Hopeful Dropped
Also on Thursday, AstraZeneca announced the discontinuation of brazikumab’s clinical development program in Crohn’s disease and ulcerative colitis.
AstraZeneca cut the candidate after conducting a “recent review of brazikumab’s development timeline,” which had been “impacted by delays that could not be mitigated,” according to the company’s news release. The discontinuation was also in consideration of “a competitive landscape that has continued to evolve.”
There were no safety concerns that contributed to brazikumab’s discontinuation.
Brazikumab is an investigational antibody designed to target and bind to the IL-23 protein and block its interaction with its corresponding receptor. This mechanism of action allowed brazikumab to ease gut inflammation, a central pathological process in CD and UC.
Prior to Thursday’s pipeline cut, brazikumab was being assessed in the Phase IIb/III INTREPID trial, which had an enrollment target of 928 CD patients and was supposed to reach completion in June 2027. AstraZeneca was also running the Phase II EXPEDITION study in UC, which was set to enroll 256 participants and end in January 2025.
AstraZeneca was developing brazikumab with funding from AbbVie, as per a 2020 agreement. This funding will now cease following the candidate’s discontinuation.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
