Curis Inc., a drug development company seeking to develop next generation targeted small molecule drug candidates for cancer treatment, said that its collaborator Roche has submitted a Marketing Authorization Application (MAA) for vismodegib (GDC-0449, RG3616) to the European Medicines Agency (EMA).

The MAA is currently under review for the treatment of adults with advanced basal cell carcinoma (BCC) for whom surgery is considered inappropriate. Vismodegib is a first-in-class, investigational, oral medicine designed to selectively inhibit signalling in the Hedgehog pathway and is being developed by Roche and Genentech, under a collaboration agreement between Curis and Genentech, a member of the Roche Group.

Curis earned a $6 million milestone payment from Genentech as a result of the MAA submission to the EMA. If vismodegib receives Marketing Authorization by the EMA, Curis will also be entitled to receive an additional milestone payment as well as royalties on any future sales.

“We continue to be extremely pleased with Roche and Genentech's efforts in progressing vismodegib towards commercialization. Vismodegib is now under review for approval in both the United States and Europe, with an FDA PDUFA action date of March 8, 2012, in the US,” said Dan Passeri, Curis president and CEO. “Vismodegib represents a potential advance for patients suffering from this serious and debilitating form of BCC, for whom no current therapeutic alternatives are available. We continue to remain hopeful that this important treatment for advanced BCC will be approved in these territories.”

The application is based on clinical data from ERIVANCE BCC/SHH4476g, a pivotal phase II study of vismodegib in patients with advanced BCC. The results were presented at the Seventh European Association of Dermato-Oncology (EADO) Congress in July 2011 as well as at the European Multidisciplinary Cancer Congress (EMCC) in September 2011.

BCC is the most common cancer in Europe and the United States. 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. There are no approved therapies to treat advanced basal cell carcinoma.

Vismodegib is designed to selectively inhibit signalling in the Hedgehog pathway by targeting a protein called Smoothened. The Hedgehog signalling 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 signalling are seen in several different types of cancer. Abnormal signalling in the Hedgehog pathway is implicated in the more than 90 per cent of BCC cases.

Genentech is also evaluating vismodegib in a phase II trial in patients with operable forms of BCC, which opened for patient enrollment in October 2010. Furthermore, 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.

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 global clinical development, and Genentech (US), Roche (Ex-US excluding Japan and Korea) and Chugai Pharmaceuticals (Japan and Korea) 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.

Curis is committed to leveraging its innovative signalling pathway drug technologies to seek to create new targeted small molecule drug candidates for cancer.