Drug Pipeline Series: Submissions---Oct16-Oct23, 2006

ROCHE FILES IN EUROPE FOR HERCEPTIN IN ADVANCED BREAST CANCER
Roche has submitted a marketing authorization application to the European Medicines Agency (EMEA) for Herceptin (trastuzumab) as treatment for advanced HER2-positive and hormone-receptor-positive breast cancer. The application is based on data from the international TAnDEM study, which showed that the addition of Herceptin to hormonal therapy doubles the median progression-free survival, from 2. 4 months to 4.8 months.
HER2-positive breast cancer is an aggressive form of the disease that requires special and immediate attention because the tumors are fast-growing and there is a higher likelihood of relapse. Up to a half of HER2-positive breast cancers are also hormone-receptor-positive, a form of the disease that has typically been considered lower risk, due to successful treatment with hormonal therapies. However, TAnDEM is the first randomized study to show that this specific subset of co-positive patients (both HER2- and hormone receptor positive) is actually higher-risk, making the positive results with Herceptin even more meaningful.
TAnDEM is Phase III trial that evaluated Herceptin in combination with the hormonal therapy anastrozole versus anastrozole alone as first-line therapy (or second-line hormonal therapy) in postmenopausal women with advanced (metastatic), HER2-positive and hormone-receptor-positive breast cancer. Enrolment to the trial began in 2001, and 208 HER2 and hormone-receptor co-positive patients were randomized at 77 centers in 22 countries.
Median progression-free survival, the primary endpoint of the trial, was 4.8 months for patients who received the combination compared with 2.4 months for patients who received hormonal therapy alone. Patients in the combination arm also responded significantly better to treatment (overall response rate was 20.3 percent versus 6.8 percent. There was also a positive trend in median overall survival (28.5 months versus 23.9 months), despite the fact that in the hormonal therapy alone arm, more than half of patients crossed over to receive Herceptin during the trial when their disease had progressed, and an additional 15 patients received Herceptin at a later time point.

GW Files Sativex Regulatory Submission In Canada For Cancer Pain
GW Pharmaceuticals plc and Bayer HealthCare, Pharmaceuticals Division - Canada ("Bayer") announce that GW has submitted a regulatory application in Canada for Sativex® to seek approval for a new indication for the treatment of pain in patients with advanced cancer that has not been adequately relieved by opioid medications.
This submission follows a formal pre-submission meeting recently held with Health Canada outlining the evidence of effectiveness of Sativex in this very seriously ill patient population. Following this meeting, Health Canada advised that, on the basis of the clinical data presented, that a submission for consideration under the Notice of Compliance with Conditions (NOC/c) policy could be made. Dr Geoffrey Guy, GW's Chairman, said: "This regulatory submission represents a further step in our broad-based regulatory strategy for Sativex, which is designed to secure approvals for this important new medicine across a range of separate therapeutic indications in countries across the world over the coming years." GW has completed a positive Phase III study in Europe in 177 patients with cancer pain. The trial was a multi-centre double-blind, randomized, placebo-controlled parallel group study. Patients in the study had advanced cancer and were experiencing pain that was not responding adequately to strong opioid medication (e.g. morphine). In addition to study medication, all patients remained on their existing opioid and other analgesic medication during the trial. In this study, Sativex achieved a statistically significant improvement in comparison with placebo in pain as measured on a numerical rating scale (p=0.014), a primary endpoint of the study. A responder analysis showed that 43 per cent of patients on Sativex showed a greater than 30 per cent improvement in their pain (p=0.024). Cancer-related pain can be defined as pain caused by cancer, by cancer treatment such as surgery, radiation therapy or chemotherapy, or by the side effects of treatment. Severe pain is experienced by at least two thirds of patients with advanced disease. It is estimated that between 14 per cent and 47 per cent of these patients will achieve inadequate pain relief from opioid based approaches and will continue to suffer pain.(1)