New class of treatment in advanced breast cancer

Pharma News: Researchers at the University of Adelaide have found new evidence about the positive role of androgens in breast cancer treatment for women with estrogen receptor-driven metastatic disease.

“This work has immediate implications for women with metastatic estrogen receptor positive breast cancer, including those resistant to current forms of endocrine therapy,’’ said Associate Professor Theresa Hickey, Head of the Breast Cancer Group and one of the study leads.

Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories, said “We provide compelling new evidence that androgen receptor (AR) stimulating drugs can be more effective than Tamoxifen or new standard-of-care treatments such as Pfizer’s Ibrance (Palbociclib) and, in the case of the latter, can be combined to enhance growth inhibition.

Using cell-line and patient-derived models, a global team, including researchers at the University of Adelaide and the Garvan Institute, demonstrated that androgen receptor activation by natural androgen or a new androgenic drug had potent anti-tumour activity in all estrogen receptor positive breast cancers, even those resistant to current standard-of-care treatments.

Currently available selective androgen receptor activating agents lack the undesirable side effects of natural androgens, and can confer benefits in women including promotion of bone, muscle and mental health.

Associate Professor Elgene Lim, a breast oncologist and Head of the Connie Johnson Breast Cancer Research Lab at the Garvan Institute, said “Given the efficacy of this treatment strategy at multiple stages of disease in our study, we hope to translate these findings into clinical trials as a new class of endocrine therapy for breast cancer.”

An international Phase 3 registration clinical trial sponsored by Veru biopharma evaluating Enobosarm, an androgen receptor activating agent, in patients with androgen receptor and estrogen receptor positive metastatic breast cancer who failed endocrine therapy and a CDK 4/6 inhibitor, for example, Ibrance (palbociclib), will commence in the second quarter of 2021.

“Enobosarm represents the first new class of endocrine therapy for advanced breast cancer in decades. By targeting the AR in ER+ HER2- metastatic breast cancer, enobosarm introduces a novel endocrine therapy to patients with breast cancer that have exhausted endocrine therapies targeting ER, but prior to IV chemotherapy. We have successfully completed the exclusive in-license of full worldwide rights to enobosarm,” said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru.

“We are also pleased to have reached agreement with the FDA to initiate a single Phase 3 enobosarm ‘ARTEST’ registration clinical trial in ER+/HER2- metastatic breast cancer, which we expect to commence in the first half of calendar year 2021. Enobosarm has strong intellectual property protection with composition of matter patent expiry in 2029 and with possible 5-year patent extension to 2034 and method of use for breast cancer patents expiry 2034. The global annual market for an oral agent in an ER endocrine resistant setting is estimated to be $6 billion,” he added.

Dr Stephen Birrell, a breast cancer specialist and pioneer in androgens and women’s health who was part of the Adelaide based team, pointed out that this seminal finding has application beyond the treatment of breast cancer, including breast cancer prevention and treatment of other disorders also driven by estrogen.