Astellas Pharma and Pfizer announced results from the Phase III PROSPER trial in patients with non-metastatic (M0) Castration-Resistant Prostate Cancer (CRPC). The Phase III randomized, double-blind, placebo-controlled, multi-national trial enrolled approximately 1,400 patients with M0 CRPC. The primary endpoint of the PROSPER trial, metastasis-free survival (MFS), is a measure of the amount of time that passes until a cancer can be radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation. Secondary endpoints included time to PSA progression, time to first use of antineoplastic therapy and overall survival. The results show that the use of XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) significantly reduced the risk of developing metastases or death by 71 percent compared to ADT alone. The median for the primary endpoint MFS, was 36.6 months for men who received XTANDI compared to 14.7 months with ADT alone (n=1401; HR=0.29 [95 percent CI: 0.24-0.35]; p<0.0001). XTANDI plus ADT prolonged the median time to first use of new antineoplastic therapy by 21.9 months versus ADT alone (39.6 months [95 percent CI: 37.7-NR] vs. 17.7 months [95 percent CI: 16.2-19.7]), a 79 percent relative risk reduction (HR=0.21 [95 percent CI: 0.17-0.26]; p<0.0001). Marketing applications based on the results of the PROSPER study have been submitted to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Allergan announced positive results from ACHIEVE I (UBR-MD-01), the first of two pivotal phase III clinical trials evaluating the efficacy, safety and tolerability of orally administered ubrogepant 50 mg and ubrogepant 100 mg compared to placebo in a single migraine attack in adults. The ACHIEVE I study included 1327 U.S. adult patients randomized (1:1:1) to placebo, ubrogepant 50 mg and 100 mg respectively, who were treated for a single migraine attack of moderate to severe headache intensity. The ACHIEVE I trial is a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The co-primary efficacy parameters were pain freedom (PF) at two hours after the initial dose and absence of the most bothersome migraine-associated symptom (photophobia, phonophobia or nausea) at two hours after the initial dose. Both doses showed a statistically significant greater percentage of ubrogepant patients achieving pain freedom at two hours after the initial dose as compared to placebo patients (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0003) and a statistically significant greater percentage of ubrogepant patients achieving absence of the most bothersome migraine-associated symptom at two hours after the initial dose as compared to placebo patients (50 mg vs placebo, p=0.0023, 100 mg vs placebo, p=0.0023). Ubrogepant was well tolerated with an adverse event profile similar to placebo. The most common adverse events were nausea, somnolence, and dry mouth, none of which were reported with a frequency of ≥5 percent.
Genentech announced results from the positive Phase III IMmotion151 study of TECENTRIQ and Avastin (bevacizumab) as a first-line treatment for advanced or metastatic renal cell carcinoma (mRCC). IMmotion151 is a Phase III multicenter, randomized, open-label study to evaluate the efficacy and safety of TECENTRIQ and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. The study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: expression ≥ 1 percent) protein. Those who received TECENTRIQ plus Avastin had a 26-percent reduced risk of disease worsening or death (PFS) compared to people treated with sunitinib (median PFS [mPFS]: 11.2 vs. 7.7 months; HR=0.74; 95 percent CI 0.57, 0.96; p=0.02). Safety for the TECENTRIQ and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination. The rate of treatment-related Grade 3-4 adverse events was lower with the TECENTRIQ and Avastin combination (40 percent) than with sunitinib alone (54 percent) in all treated patients.