exelixis inc (EXEL) Snapshot

Exelixis, Inc. Presents at William Blair & Company 33(rd) Annual Growth Stock Conference, Jun-12-2013 02:00 PM. Venue: Four Seasons Hotel, Chicago, Illinois, United States. Speakers: Michael M. Morrissey, Chief Executive Officer, President and Director.

Exelixis, Inc. announced the presentation of additional data from clinical trials of COMETRIQ (cabozantinib) in patients with progressive, metastatic medullary thyroid cancer (MTC). The data were presented this weekend at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO). Long-term follow-up of a phase 1 trial shows that 30% of progressive, metastatic MTC patients treated with COMETRIQ experienced disease control (DC) and have remained progression-free for more than 2 years. A separate presentation reports data from the prospective analysis of RET mutational status and retrospective ad hoc analysis of RAS mutational status of patients in EXAM, Exelixis' phase 3 pivotal trial of COMETRIQ in progressive, metastatic MTC. These data show improvement in progression-free survival (PFS) with COMETRIQ treatment compared to placebo in all genetically defined subgroups, with a greater effect on PFS seen in the RET mutation positive and RET mutation unknown subgroups. The U.S. Food & Drug Administration approved COMETRIQ for the treatment of progressive, metastatic MTC in November 2012. The label allows for use of COMETRIQ in progressive, metastatic MTC without regard to mutation status. Ezra Cohen, M.D., Associate Professor of Medicine at the University of Chicago, Department of Medicine, Associate Director for Education at the University of Chicago Comprehensive Cancer Center, and a principal investigator on the COMETRIQ phase 1 study, presented long-term follow-up data for the cohort of MTC patients included in the study in a poster session on June 1. Of 85 patients enrolled in the phase 1 study, 37 had metastatic or locally advanced MTC. After a minimum follow-up of 52 months, 11 of the 37 patients (30%) experienced long term disease control (DC), defined as confirmed partial response (cPR) or progression free >= 24 months. Time from diagnosis and time since development of metastatic disease was similar between patients with or without long-term DC. The most frequent adverse events associated with COMETRIQ were diarrhea, fatigue, nausea, and decreased appetite. The adverse event profile observed after 1 year of treatment was generally consistent with that seen during any time of treatment with COMETRIQ. The median final COMETRIQ dose for patients with long-term DC was 60 mg (range: 20-140 mg), and the median number of dose reductions was 2 (range: 0-4). Dr. Steven I. Sherman, M.D., Naguib Samaan Distinguished Professor in Endocrinology at M.D. Anderson Cancer Center and Chairman of the International Thyroid Oncology Group, presented the phase 3 mutational analysis data in an oral session on Sunday, June 2. RET and RAS mutations were assessed in patients enrolled in EXAM, a double blind, placebo-controlled, phase 3 trial of COMETRIQ in patients with progressive, metastatic MTC. The median PFS on the COMETRIQ arm was 11.2 months, compared with 4 months for the placebo arm, HR 0.28, 95% CI 0.19, 0.40, p < 0.0001. RET status was determined in 65% (215/330) of the patients enrolled in the phase 3 trial. Of these 215 patients, 79% had activating RET mutations and 21% had no RET mutations detected. Of 85 evaluated patients with either no RET mutations or unknown RET status, 16 were found to have a RAS gene mutation. COMETRIQ had activity across all RET and RAS mutational subgroups, and demonstrated response rates of 22-32%, consistent with the response rate of patients in the study overall (28% COMETRIQ vs. 0% placebo). Patients with RET mutations had significantly longer median PFS (60 weeks) than patients who were RET mutation-negative (25 weeks). Patients with RAS mutations had a median PFS of 47 weeks, indicating that clinical activity measured in the RET mutation-negative subgroup can be attributed partially to patients with RAS mutations. COMETRIQ's safety and efficacy was assessed in an international, multi-center, randomized double-blinded controlled trial called EXAM of 330 patients with progressive, metastatic medullary thyroid carcinoma (MTC). Patients were required to have evidence of actively progressive disease within 14 months prior to study entry confirmed by an Independent Radiology Review Committee (IRRC) masked to treatment assignment (89%) or the treating physician (11%). Patients were randomized (2:1) to receive COMETRIQ 140 mg (n = 219) or placebo (n = 111) orally, once daily until disease progression determined by the treating physician or until intolerable toxicity. Randomization was stratified by age (<=65 years vs. > 65 years) and prior use of a tyrosine kinase inhibitor (TKI). No crossover was allowed at the time of progression. The main efficacy outcome measures of PFS, objective response and response duration were based on IRRC-confirmed events using the modified RECIST criteria. A statistically significant prolongation in PFS was demonstrated among COMETRIQ-treated patients compared to those receiving placebo [HR 0.28 (95% CI: 0.19, 0.40); p<0.0001], with median PFS times of 11.2 months and 4.0 months in the COMETRIQ and placebo arms, respectively. Partial responses were observed only among patients in the COMETRIQ arm (27% vs 0; p<0.0001). The median duration of objective responses was 14.7 months (95% CI: 11.1, 19.3) for patients treated with COMETRIQ. There was no statistically significant difference in overall survival between the treatment arms at the planned interim analysis.

Exelixis, Inc. announced the presentation of updated interim data from 144 docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases treated with cabozantinib in an ongoing non-randomized expansion (NRE) cohort of its phase 2 randomized discontinuation trial. Median overall survival was 10.8 months in a patient population in which 73% of patients had received two or more prior therapies including docetaxel and abiraterone, enzalutamide, and/or cabazitaxel. Furthermore, a retrospective analysis of the interim data shows that early responses in bone scan, circulating tumor cell (CTC) levels, and pain are associated with longer median overall survival (OS) as compared to non-responders. These post hoc findings, particularly the bone scan response results, support the rationale for potential future prospective validation of the association of bone scan response with OS in the company's ongoing phase 3 COMET trials in mCRPC. The interim results presented was comprise data from 144 men with mCRPC in the NRE cohort of an ongoing phase 2 randomized discontinuation trial. All patients had disease progression in either bone or soft tissue disease within 6 months of completion of docetaxel treatment, and the protocol differed from typical CRPC studies in that it excluded patients who progressed by PSA criteria alone, who generally have a better overall prognosis. All patients also had bone metastases on bone scan and 31% had measurable soft tissue disease. 73% of patients had received at least two prior lines of therapy for mCRPC, including docetaxel in all patients. In 36% of patients, disease progression was very rapid, occurring less than one month following the last dose of taxane therapy. Clinically significant pain, defined as baseline pain score by Brief Pain Inventory (BPI) >= 4, was present in 47% of patients. 80% of patients had a CTC count >= 5/7.5 mL of blood. Patients received a 100 mg or 40 mg daily dose of cabozantinib. The median OS in the 144 patients was 10.8 months (95% confidence interval 9.1-13.0). Bone scan response (>= 30% decrease from baseline in the Technetium-99m methylene diphosphonate bone scan lesion area determined by computer assisted detection) was observed in 65% of evaluable patients, CTC response (conversion from >= 5 CTC/7.5 mL of blood to < 5 CTC/7.5 mL of blood) in 32% of evaluable patients, and pain response (>= 30% decrease from baseline in worst pain observed at 2 consecutive assessments >= 6 weeks apart) in 43% of evaluable patients. In univariate analyses, longer OS was associated with bone scan response at week 6, CTC response at week 6, and pain response. These findings were further examined and confirmed in sensitivity analyses after adjusting for significant baseline covariates, such as LDH, presence or absence of visceral metastasis, and bone scan lesion area (bone disease burden), which were selected from a stepwise Cox regression model.