Merck obtains exclusive global rights to CYP11A1 inhibitor in mCRPC

Orion Corporation and Merck have mutually agreed to exercise an option that would grant Merck an exclusive global license to develop and commercialize therapeutic candidates targeting CYP11A1, including the investigational CYP11A1 inhibitor MK-5684/ODM-208 (opevesostat) for patients with metastatic castration-resistant prostate cancer (mCRPC).

"We will continue to advance the clinical development program for opevesostat with speed and rigor to help address the needs of patients living with prostate cancer," says Dean Y. Li, MD, PhD.

Prior to this announcement, the 2 companies were involved in a collaboration agreement for the co-development and co-commercialization of the CYP11A1 inhibitor in mCRPC.

“The conversion of this collaboration into a license agreement allows Orion to focus our resources to progress our other promising development candidates while both remaining well positioned to benefit from the development and potential commercialization of opevesostat and meeting our financial objectives,” said Lisa Hurme, president and chief executive officer of Orion Corporation, in a news release.¹ “We believe Merck provides the best choice to maximize the potential of opevesostat, a compound discovered by Orion’s scientists, for the treatment of patients with certain types of prostate cancer.”

According to the news release,¹ “The exclusive global license is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions, and is expected to become effective in the third quarter of 2024.”

MK-5684/ODM-208 is an oral, non-steroidal, and selective CYP11A1 inhibitor currently under investigation in the phase 3 OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650) trials, which were initiated in 2023.

The OMAHA1 trial is exploring the therapy as a later-line treatment option for patients with mCRPC who have failed 1 prior next-generation hormonal agent (NHA) and 1 or 2 prior taxane-based chemotherapies. For the study, approximately 1200 patients enrolled across international clinical trial sites will be randomly assigned to receive MK-5684/ODM-208 in combination with hormone replacement therapy (HRT) or to an alternative NHA, consisting of abiraterone acetate (Zytiga) or enzalutamide (Xtandi).

The primary end points for the trial are overall survival OS) and radiographic progression-free survival (rPFS) per RECIST v1.1 in androgen receptor ligand-binding domain (AR LBD) mutation-positive and -negative patients. Secondary outcome measures of interest include the time to subsequent therapy (TFST), the objective response rate (ORR), and the duration of response (DOR).

Final results from the trial are expected in 2028.²

The open-label OMAHA2a study plans to enroll approximately 1500 patients with mCRPC who have failed 1 prior NHA. Those included in the study will be randomly assigned to receive front-line MK-5684/ODM-208 in combination with HRT or to a physician’s choice of NHA with abiraterone acetate or enzalutamide. The primary end points for the trial are OS and rPFS in AR LBD mutation-positive and -negative patients. The trial’s secondary end points are TFST, ORR, and DOR.

The investigators anticipate having final results from the study in 2030.³

In addition to the OMAHA studies, the therapy is also being assessed in the phase 1/2a CYPIDES trial (NCT03436485), which published results from the first part of the study earlier this year. Overall, data showed that MK-5684/ODM-208 potently inhibits steroid-hormone biosynthesis with demonstrated evidence of antitumor activity in heavily pretreated patients with mCRPC.⁴ Completion of the study is expected at the end of this year.⁵

Dean Y. Li, MD, PhD, president of Merck Research Laboratories, added in the news release,¹ “We are pleased with the progress made to date in our collaboration with Orion, including the initiation of 2 pivotal phase 3 trials evaluating opevesostat in certain patients with metastatic castration-resistant prostate cancer. We will continue to advance the clinical development program for opevesostat with speed and rigor to help address the needs of patients living with prostate cancer.”

References

1. Merck and Orion announce mutual exercise of option providing Merck global exclusive rights to opevesostat, an investigational CYP11A1 inhibitor, for the treatment of metastatic castration-resistant prostate cancer. News release. Merck. July 1, 2024. Accessed July 3, 2024. https://www.merck.com/news/merck-and-orion-announce-mutual-exercise-of-option-providing-merck-global-exclusive-rights-to-opevesostat-an-investigational-cyp11a1-inhibitor-for-the-treatment-of-metastatic-castration-resistant-pr/

2. Study of opevesostat (MK-5684) versus alternative NHA in mCRPC (MK-5684-003). ClinicalTrials.gov. Last updated June 27, 2024. Accessed July 3, 2024. https://clinicaltrials.gov/study/NCT06136624

3. A study of opevesostat (MK-5684) versus alternative next-generation hormonal agent (NHA) in metastatic castration-resistant prostate cancer (mCRPC) post one NHA (MK-5684-004). ClinicalTrials.gov. Last updated June 27, 2024. Accessed July 3, 2024. https://clinicaltrials.gov/study/NCT06136650

4. Fizazi K, Bernard-Tessier A, Roubaud G, et al. Targeted inhibition of CYP11A1 in castration-resistant prostate cancer. NEJM Evid. 2024;3(1). doi:10.1056/EVIDoa2300171

5. Safety and pharmacokinetics of ODM-208 in patients with metastatic castration-resistant prostate cancer (CYPIDES). ClinicalTrials.gov. Last updated January 29, 2024. Accessed July 3, 2024. https://clinicaltrials.gov/study/NCT03436485