Curis, Inc. (CRIS-OUTPERFORM): Erivedge ERIVANCE 24-month Update - Upside in New Indications for Erivedge - '427 Clinical Hold Lifting Soon - Reiterate OUTPERFORM
Price: $2.82 Price Target: $6.00
At the American Academy of Dermatology annual meeting (March 21-25, Denver, CO) Curis and partner Roche presented data from two studies of Erivedge in Basal Cell Carcinoma (BCC), one in operable BCC and a 24-month update from the pivotal trial, ERIVANCE, in metastatic and locally advanced Basal Cell Carcinoma (BCC).
ERIVANCE Data Update: 24-months follow-up data after the primary analysis at 9-months (Sekulic 2012) revealed that one further patient in the ERIVANCE metastatic Basal Cell Carcinoma (mBCC) arm responded to treatment, increasing the investigator-assessed ORR to 48.5% from 45.5% (pages 3-4). ERIVANCE enrolled 104 pts with locally adv. BCC (laBCC, n=63) or metastatic BCC (mBCC, n=33) in two cohorts to investigate the safety and efficacy of Erivedge.
Operable BCC Data from Cohorts 2 & 3: In a Phase II trial of Erivedge in operable BCC, treatment resulted in complete histological clearance (CHC) in 42% of patients in cohort 1 (Gross 2012), 44% of patients in cohort 3 and durable CHC in 16% of patients in cohort 2 (pages 5-6). Results presented at AAD did not meet the predefined criteria of 50% CHC in cohorts 1 and 3 and 30% CHC in cohort 2. This Phase II trial enrolled 74 patients with nodular, operable, BCC to test three different dosing schedules of Erivedge. Patients received in cohort 1: 150 mg/day for 12 weeks, cohort 2: 150 mg/day 24 weeks and cohort 3: 150 mg/day for 8 weeks followed by a 4 week holiday and another 8 weeks of treatment, for a 20 week treatment cycle.
Erivedge revenues continue to track towards our 2014 estimates of $110M. We believe their remains potentially significant upside to Erivedge sales in BCC as the U.S. market is more deeply penetrated and as EU sales begin to materialize. Even in light of recently presented data we note that the current on-label opportunity for Erivedge in the U.S. and pending EU launch is large, representing 12,000 patients in the top-5 jurisdictions, we believe there is upside to Erivedge sales in 2014 and 2015.
We reiterate our belief that Erivedge will find broad use in oncology as the only available hedgehog pathway inhibitor. We see the future of chemotherapy moving toward combination therapy to increase efficacy and ameliorate the poor safety profile of many effective anti-cancer drugs. Erivedge is currently being test in combination with Avastin, Erbitux, Notch inhibitors (RO4929097) and multiple chemotherapy regimes including FOLFOX, FOLFIRI, gemcitabine and cisplatin.
Aberrant reactivation of hedgehog signaling has been described in a wide variety of human cancers, including cancer stem cells, and is differentiated from the genetic mutations in the hedgehog pathway that drive basal cell carcinomas. Most notably, recent studies have suggested that ligand-dependent abnormal signaling in the hedgehog pathway may be associated with the proliferation of AML and MDS cells.
We anticipate that the next significant catalyst for CRIS is lifting of partial clinical hold on CUDC-427 in Q1:14. Our checks suggest that CRIS has submitted a compressive data package to the FDA and included new dosing schedule details (more like the Roche Phase I) and risk-mitigation strategies for future trials of '427 in combination with capecitabine.
Curis will be presenting preclinical data for CUDC-907 (Abs #1879) and CUDC-427 (Abs #917) at the American Association for Cancer Research -- AACR, April 5-9, 2014 (San Diego, CA).
We reiterate our OUTPERFORM rating and 12-month price target of $6/share.
Deeper AAD Data Review and Erivedge Trial Summary Pages 3-8 of Note