Curis, Inc. (NASDAQ: CRIS), a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced that its collaborator Genentech, a member of the Roche Group, has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking sales and marketing approval for vismodegib (GDC-0449, RG3616) to treat people with advanced basal cell carcinoma (BCC), which includes metastatic and locally advanced BCC for whom surgery is inappropriate. Vismodegib is a first-in-class investigational, oral medicine designed to selectively inhibit signaling in the Hedgehog pathway, which is implicated in more than 90 percent of BCC cases. Curis is eligible to receive an $8 million milestone payment from Genentech upon FDA acceptance of this submission. If the drug receives FDA approval, then Curis will also be entitled to receive an additional milestone payment as well as royalties on any future sales. “We continue to be impressed by Genentech’s development efforts with respect to this molecule and are pleased that, following its successful completion of a pivotal study in advanced BCC, the vismodegib program has advanced to a U.S. NDA submission,” said Dan Passeri, Curis President and Chief Executive Officer. “We believe that vismodegib is an excellent example of a targeted cancer drug that has been developed based on an understanding of the underlying molecular biology that drives the disease. We believe that this molecule has the potential to provide an important treatment option for patients with advanced BCC.” Curis expects that the FDA will notify Genentech whether its NDA submission has been accepted for filing within 60 days of submission. Assuming the FDA accepts the NDA submission, the agency will communicate a PDUFA date to Genentech. Roche has also indicated that the timing of a European regulatory submission is subject to its ongoing discussions with the European Medicines Agency (EMA). Curis is entitled to receive an additional milestone payment should such submission be made by Roche and subsequently accepted by EMA, as well a milestone payment and royalties on future sales should vismodegib be approved by EMA.
About the Pivotal Phase II Trial (ERIVANCE BCC/SHH4476g)ERIVANCE BCC is an international, single-arm, multicenter, two-cohort, open-label Phase II study that enrolled 104 patients with advanced BCC, including locally advanced BCC (71) and metastatic BCC (33). Locally advanced BCC includes patients whose BCC lesions are deemed inoperable or for whom surgery is deemed inappropriate. Metastatic BCC is defined as BCC that had spread to other parts of the body, including the lymph nodes, lung, bones and/or internal organs. The study was conducted at 31 sites in the United States, Australia and Europe. Study participants received 150 mg vismodegib orally, once daily until disease progression or intolerable toxicity. Tumor responses for metastatic BCC were measured by RECIST criteria and for locally advanced BCC by a novel composite endpoint which included reduction of size of lesions of at least 30% in longest dimension and/or complete resolution of locally advanced BCC ulceration. The primary endpoint of the study is overall response rate as assessed by an independent review facility, with secondary endpoints including investigator-assessed overall response rate, progression-free survival (PFS), overall survival (OS), and duration of response in all evaluable patients, including locally advanced BCC or metastatic BCC patients. In addition, absence of residual BCC in patients was assessed by sampling biopsies in patients with locally advanced BCC. The overall response rate in the pivotal Phase II trial as assessed by an independent review facility showed vismodegib substantially shrank tumors or healed visible lesions in 43 percent of patients in the locally advanced cohort and 30 percent of patients in the metastatic BCC cohort. The median duration of progression-free survival (PFS) by independent review for both metastatic BCC and locally advanced BCC patients was 9.5 months. The median duration of response by independent review was 7.6 months for both metastatic BCC and locally advanced BCC patients. The median duration of response as assessed by study investigators was 12.9 and 7.6 months for metastatic BCC and locally advanced BCC patients, respectively.
There was no residual BCC in sampling biopsies of 54% of locally advanced BCC patients.As of the November 26, 2010, data cutoff date, there were 19 (57.6%) metastatic BCC and 32 (45.1%) locally advanced BCC patients remaining on treatment. The median duration on treatment as of this date was 10 and 9.7 months for metastatic BCC and locally advanced BCC patients, respectively. The most common adverse events observed in the study (observed in greater than 20% of patients) included muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite, and diarrhea. Serious adverse events (SAEs) were observed in 26 patients (25 percent). Four of these patients (4 percent) had SAEs that were considered to be related to vismodegib, including one case each of: blocked bile flow from the liver (cholestasis), dehydration with loss of consciousness (syncope), pneumonia accompanied by an inability of the heart to pump enough blood (cardiac failure) and a sudden arterial blockage in the lung (pulmonary embolism). Fatal events were reported in seven patients (7 percent); none were considered by investigators to be related to vismodegib. In all fatalities, pre-existing risk factors and comorbid conditions were present. About Basal Cell Carcinoma BCC is the most common cancer in the United States and the most common type of skin cancer, accounting for approximately two million new cases annually. The disease is generally considered curable when the cancer is restricted to a small area of the skin. However, in a small group of people, if the disease is left untreated or does not respond to treatment, the cancer may advance further into the skin, bones or other tissues, or spread to other parts of the body. In such rare cases, the disease can become difficult to treat and life-threatening. About Vismodegib and the Hedgehog Pathway Vismodegib is designed to selectively inhibit signaling in the Hedgehog pathway by targeting a protein called Smoothened. The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and becomes less active in adults. However, mutations in the pathway that reactivate Hedgehog signaling are seen in several different types of cancer. Abnormal signaling in the Hedgehog pathway is implicated in the majority of BCC cases.
Genentech is also evaluating vismodegib in a Phase II trial in people with operable forms of BCC, which opened for patient enrollment in October 2010. Additionally, vismodegib is being evaluated by third-party investigators in a number of other cancers and in people with BCC who have Gorlin syndrome, a condition that affects many areas of the body and increases the risk of developing BCC. For more information, visit http://www.clinicaltrials.gov.About the Curis-Genentech Collaboration Under the ongoing collaboration agreement between Genentech, a wholly owned member of the Roche Group, and Curis, vismodegib (GDC-0449, RG3616) was discovered by Genentech and was jointly validated by the parties through a series of preclinical studies. Pursuant to this collaboration, Genentech and Roche are responsible for clinical development, and Genentech (U.S.), Roche (Ex-U.S. excluding Japan) and Chugai Pharmaceuticals (Japan) are responsible for commercialization of vismodegib. Curis is eligible to receive cash payments upon the successful achievement of specified clinical development and regulatory approval milestones, as well as royalties assuming successful commercialization of vismodegib by Genentech and its sublicensees, which include Roche and Chugai. About Curis, Inc. Curis is a drug development company that is committed to leveraging its innovative signaling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer. Curis is building upon its previous experiences in targeting signaling pathways, including the Hedgehog pathway, in its effort to develop proprietary targeted cancer programs. For more information, visit Curis' website at www.curis.com. Curis Cautionary Statement: This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding: Genentech and Roche’s planned regulatory submissions for vismodegib; the potential favorable safety and efficacy profile of vismodegib; and the potential for vismodegib to have a compelling clinical benefit in treating advanced BCC patients and to be an important new treatment for cancer. Forward-looking statements used in this press release may contain the words "believes", "expects", "anticipates", "plans", "seeks", "estimates", "assumes", "will", "may," “could” or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements including, among other things:
- The FDA may reject Genentech’s NDA submission for vismodegib if it determines that the submission has failed to meet the FDA’s filing requirements.
- Roche may not make a regulatory submission to the EMA, and, even if a submission is made, the EMA may not accept any such application if it fails to meet the EMA’s filing requirements.
- Genentech and Roche may not demonstrate to the satisfaction of the FDA or any comparable foreign regulatory agency the safety and efficacy profile of vismodegib in the treatment of advanced BCC, in which case vismodegib will not be approved for sales and marketing for the treatment of such indication.
- Genentech and Roche may not be able to replicate in later trials any favorable safety and efficacy data from earlier trials of vismodegib in other indications, or may otherwise fail to meet applicable regulatory standards for approval of vismodegib in other indications.
- Even if vismodegib receives marketing authorization, its benefit/risk profile may not be widely accepted by the medical community or third party payors for the treatment of advanced BCC.
- Curis or Genentech may not be able to obtain or maintain the intellectual property protection necessary for the development and commercialization of vismodegib.
- Genentech has significant discretion in determining the efforts and resources it will apply to its collaboration with Curis, and has the right to terminate the collaboration on short notice under specified circumstances. As such, the timing and amount of cash payments the Company could receive under the collaboration, and the successful commercialization of vismodegib, will depend solely on Genentech’s and its sublicensees’ efforts and allocation of resources to the development and commercialization of vismodegib.
- Curis also faces other important risks relating to the successful development and commercialization of vismodegib, and with respect to its business, operations, financial condition and future prospects generally, that are discussed in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2011 and other filings that it periodically makes with the Securities and Exchange Commission.