Curis Announces Presentation of Positive Vismodegib Pivotal Clinical Data in Advanced Basal Cell Carcinoma

Update: Erivedge (vismodegib) Now FDA Approved - January 30, 2012

-- Collaborator Genentech presenting data demonstrating vismodegib helped shrink tumors or heal lesions in advanced basal cell carcinoma patients --

LEXINGTON, Mass.--(BUSINESS WIRE)--Jun 20, 2011 - Curis, Inc. (NASDAQ: CRIS), a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, today announced that positive data are being presented by its collaborator Genentech, a member of the Roche Group, from a pivotal Phase II clinical trial conducted by Roche and Genentech of vismodegib (GDC-0449, RG3616) in patients with advanced basal cell carcinoma (BCC), an often life-threatening form of skin cancer that can have disfiguring and debilitating effects. The results will be presented on June 21st at the Seventh European Association of Dermato-Oncology (EADO) Congress taking place in Nantes, France.

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. Genentech has indicated that it anticipates submitting a new drug application to the U.S. Food and Drug Administration (FDA) in 2011 to seek approval to commercialize vismodegib based on the positive outcome of this study. Roche has indicated that the timing of a European regulatory submission is subject to planned discussions with the European Medicines Agency (EMA).

"We believe that the strength of the data generated in this clinical study, including the overall response rates observed, demonstrate the potential for vismodegib to have a compelling clinical benefit in treating advanced BCC patients,” said Dan Passeri, Curis President and Chief Executive Officer. “Vismodegib has the potential to be an important new treatment for cancer patients with this debilitating condition and we are pleased to see the molecule reach this critical stage of development. We continue to look forward to Genentech and Roche's upcoming regulatory submissions for vismodegib in this patient population.”

Vismodegib Pivotal Phase II Results

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 (IaBCC) or metastatic BCC (mBCC) patients. In addition, absence of residual BCC in patients was assessed by sampling biopsies in patients with laBCC.

Genentech had previously reported Phase I clinical trial results in the New England Journal of Medicine in which an investigator-assessed response rate of 55 percent was observed in 33 patients with advanced BCC treated with vismodegib, including those with IaBCC or mBCC. In the pivotal Phase II trial, study investigators assessed the overall response rate to be 55 percent, with 60 percent in the laBCC cohort, and 46 percent in mBCC cohort.

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, with observed response rates of 43 percent of patients in the laBCC cohort and 30 percent of patients in the mBCC cohort.

The clinical benefit rate (defined as patients who experienced response as well as those who experienced prolonged stable disease for more than 24 weeks) showed vismodegib shrank tumors or healed visible lesions, or prevented them from growing any further in 75 percent of patients with laBCC and 76 percent of patients with mBCC, as assessed by independent review.

The median duration of progression-free survival (PFS) by independent review for both mBCC and laBCC patients was 9.5 months. The median duration of response by independent review was 7.6 months for both mBCC and laBCC patients. The median duration of response as assessed by study investigators was 12.9 and 7.6 months for mBCC and laBCC patients, respectively.

There was no residual BCC in sampling biopsies of 54% of laBCC patients.

As of the November 26, 2010, data cutoff date, there were 19 (57.6%) mBCC and 32 (45.1%) laBCC patients remaining on treatment. The median duration on treatment as of this date was 10 and 9.7 months for mBCC and laBCC patients, respectively.

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 laBCC (71) and mBCC (33). laBCC patients had lesions that were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) and for which radiotherapy was unsuccessful or contraindicated. mBCC was 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 150mg vismodegib orally, once daily until disease progression or intolerable toxicity. Tumor responses for mBCC were measured by RECIST criteria and for laBCC by a novel composite endpoint which included reduction of size of lesions of at least 30% in longest dimension and/or complete resolution of laBCC ulceration.

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:

 

  • Genentech and Roche may be delayed in making planned regulatory submissions to seek marketing approval of vismodegib for advanced BCC.
  • Genentech and Roche may not demonstrate to the satisfaction of the FDA or any comparable foreign regulatory agency the safety and efficacy of vismodegib in the treatment of advanced BCC or any other 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 March 31, 2011 and other filings that it periodically makes with the Securities and Exchange Commission.

In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis' views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise.

 

Contact: Curis, Inc.
Michael P. Gray, 617-503-6632
Chief Financial and Chief Operating Officer
mgray@curis.com

 

Posted: June 2011

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