Veru Reports Clinical Data from the Discontinued ARTEST Study of Enobosarm, Novel Selective Androgen Receptor Targeting Agonist, in AR+ ER+ HER2- Metastatic Breast Cancer
--Overall response rates of 12.5% are observed in the enobosarm group in a heavily pretreated population versus no responses in the standard of care active control arm. On average, enobosarm or active control was given in the 4(th) line treatment in the metastatic setting which included a prior CDK 4/6 inhibitor combination--
--Overall response rate was 20% for enobosarm monotherapy versus 0% for standard of care active control in patients who had =3 lines of prior endocrine therapy in the metastatic setting--
--Enobosarm was generally well tolerated with no masculinizing adverse events or hematocrit increases--
--Company believes ARTEST clinical data further validates the evaluation of enobosarm in the Phase 3 ENABLAR-2 study which is given earlier in the treatment sequence as a 2(nd) line therapy in the metastatic setting targeting a larger patient population--
MIAMI, Sept. 11, 2023 (GLOBE NEWSWIRE) -- Veru Inc. (NASDAQ: VERU), a late clinical stage biopharmaceutical company focused on developing novel medicines for metastatic breast cancer and for viral induced acute respiratory distress syndrome (ARDS), today announced clinical data from the discontinued Phase 3 ARTEST clinical trial of enobosarm monotherapy for the 3(rd) line or greater in the metastatic setting of AR+ER+HER2- breast cancer. Enrollment was discontinued in order to prioritize and focus the clinical development of enobosarm therapy earlier in the treatment sequence, the 2(nd) line metastatic setting, for AR+ER+HER2- metastatic breast cancer in the Phase 3 ENABLAR-2 (enobosarm +/- abemaciclib CDK 4/6 inhibitor) study. Data reported from the discontinued trial, which is based on an analysis of available data, may not be predictive of the results of larger, later-stage controlled clinical trials.
Highlights of clinical data from discontinued Phase 3 ARTEST clinical study
At the time enrollment was stopped, there were 34 evaluable patients randomized to either 9mg enobosarm monotherapy (n=16) or a standard of care active control (n=18) in the Phase 3 open label, randomized (1:1) clinical trial for the treatment of AR+ER+HER2- metastatic breast cancer with sufficient AR expression in their breast cancer tissue who had previously received at least a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor.
Active control treatment group received an average of 2.6 (range 1-5) and enobosarm 9mg monotherapy an average of 2.9 (range 1-5) prior lines of treatment. On average, enobosarm or the active control was given in the 4(th) line treatment for AR+ER+HER2- metastatic breast cancer.
Summary of Overall Response Rate Data*:
Enobosarm monotherapy Estrogen blocking agent active control ------------------------------ --------------------- ----------------------- Evaluable patients 2 PR /16 (12.5%) 0 PR/18 (0%) ------------------------------ --------------------- ----------------------- Evaluable patients - including 3 PR /16 (18.8%) 0 PR/18 (0%) an unconfirmed response ------------------------------ --------------------- ----------------------- Patients with =3 lines of 2 PR /10 (20%) 0 PR/15 (0%) prior endocrine therapy ------------------------------ --------------------- ----------------------- Patients with =3 lines of 2 PR /6 (33.3%) 0 PR/10 (0%) prior endocrine therapy with =1 prior treatment with CDK 4/6 inhibitor ------------------------------ --------------------- -----------------------
*unaudited data, overall response rate = partial response (PR) + complete response (CR)
Safety: Enobosarm monotherapy was generally well tolerated without masculinizing adverse events or increases in hematocrit.
"Enobosarm is a new and different hormone agent that targets the androgen receptor to suppress metastatic breast cancer with potential improvements in quality of life without the unwanted masculinizing side effects and increase in hematocrit typically associated with androgens," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru.
"The clinical results from the ARTEST study provide promising scientific support and validation for the potential of enobosarm therapy in the ongoing Phase 3 ENABLAR-2 study. The AR+ER+HER2- metastatic breast cancer patients enrolled in the Phase 3 ARTEST study were heavily pretreated. On average, either enobosarm or the standard of care active control in ARTEST was given as 4(th) line treatment. Although sicker patients and smaller sample size, the antitumor activity and safety of enobosarm are promising. Tumor response rates of 20% for enobosarm monotherapy versus 0% for active control in patients with =3 lines of prior therapy are highly encouraging because they represent a patient population that is similar to that being tested in ENABLAR-2. Additionally, this is consistent with what we observed in the Phase 2 (G200802) study where enobosarm treatment resulted in a tumor response rate of 3/10 (30%) in a subgroup of heavily pretreated ER+HER2- metastatic breast cancer patients who also had a prior CDK 4/6 inhibitor. To put these tumor response rates into context, it has been reported that treatment with either elacestrant (selective estrogen receptor degrader) or standard of care treatment in the 2(nd) line metastatic setting in ER+HER2- metastatic patients who had tumor progression following CDK 4/6 inhibitor treatment resulted in tumor response rates of about 4.5%."
"Based on the ARTEST study, our expectation for the ENABLAR-2 study is that enobosarm could have greater activity either as monotherapy or in combination with abemaciclib compared to an estrogen blocking agent active control earlier in the treatment sequence, 2(nd) line treatment, for AR+ER+HER2- metastatic breast cancer after receiving a prior CDK 4/6 inhibitor + estrogen blocking agent. In fact, in stage 1 of the ENABLAR-2 study, we have already observed 2 partial responses in the first 3 patients enrolled who were treated with enobosarm 9mg plus abemaciclib combination in the 2(nd) line metastatic setting after having tumor progression while receiving CDK 4/6 inhibitor plus an estrogen blocking agent. We are encouraged by these early results, and it appears to be the right decision to move and focus enobosarm's clinical development earlier to the 2(nd) line metastatic setting for ER+HER2- metastatic breast cancer patients in the Phase 3 ENABLAR-2 study."
About Enobosarm
Estrogen receptor (ER) is present in 85% of all breast cancers, and more than 90% of ER+ positive breast cancers also contain the AR which has been demonstrated to be an important therapeutic target in ER+ breast cancer. Enobosarm is an oral drug that selectively targets the AR in breast cancer without having the unwanted virilizing androgen adverse side effects including facial hair, acne, increase in hematocrit, or liver toxicity, while having potential clinical benefits including increasing muscle and physical function as well addressing cancer treatment induced bone loss and fractures. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies with approximately 1450 dosed patients, including three Phase 2 clinical studies in advanced breast cancer.
About Phase 3 ENABLAR-2 clinical study:
Phase 3 clinical ENABLAR-2 study -- Enobosarm +/- abemaciclib (CDK 4/6 inhibitor) combination versus estrogen blocking agent (active control) as a 2nd line treatment for AR+ ER+ HER2- metastatic breast cancer
In March 2023, the Company announced that it was prioritizing the clinical development of enobosarm in the Phase 3 ENABLAR-2 (enobosarm +/- abemaciclib CDK 4/6 inhibitor) in the 2(nd) line metastatic setting in AR+ER+HER2- breast cancer and discontinuing the Phase 3 ARTEST (enobosarm monotherapy) clinical study in the 3(rd) line metastatic setting in AR+ER+HER2- breast cancer. Reasons the company prioritized the development of enobosarm in the Phase 3 ENABLAR-2 study included:
-- The desire to focus enobosarm treatment earlier in a potentially more responsive, 2nd line metastatic setting in the sequence of therapies for patients with ER+HER2- breast cancer -- 2nd line treatment is a larger patient population than 3rd line or greater in the metastatic setting for ER+HER2- breast cancer -- The Phase 3 ENABLAR-2 and the Phase 3 ARTEST studies had an overlapping target patient population based on current and evolving standards of care, therefore closing the ARTEST study would decrease competition for the recruitment of similar patients -- Veru has a clinical collaboration and supply agreement for abemaciclib with Eli Lilly for the Phase 3 ENABLAR-2 study
On March 30, 2023, the Company met with the FDA to gain further agreement on Phase 3 clinical trial design and program. The Phase 3 study has been amended to accommodate the FDA's latest recommendations to support registration as a second line treatment for patients with AR+ ER+ HER2- metastatic breast cancer who have tumor progression while receiving a CDK 4/6 inhibitor plus an estrogen blocking agent (nonsteroidal aromatase inhibitor or selective estrogen receptor degrader). The Phase 3 ENABLAR-2 study has 2 distinct study stages: |
