GW Pharmaceuticals plc announces the initiation of the Phase III clinical trials programme of Sativex in the treatment of pain in patients with advanced cancer, who experience inadequate analgesia during optimized chronic opioid therapy. This indication represents the initial target indication for Sativex in the United States.
The Phase III programme is being performed in conjunction with GW’s licensing partner for Sativex in the US, Otsuka Pharmaceutical Co. Ltd. The programme, which is fully funded by Otsuka, includes two Phase III randomised placebo-controlled multi-centre multinational trials as well as a long term extension study. Each Phase III trial will include approximately 370 patients and will evaluate the efficacy and safety of Sativex versus placebo over a 5 week treatment period.
The primary efficacy measure of the Phase III trials is a patient assessment of pain using a 0-10 Numeric Rating Scale (NRS), and the primary analysis is the “continuous response analysis of percent improvement from baseline” (an analysis of percent improvement in pain across the spectrum of response levels). This analysis has yielded statistically0 significant results in both the Phase II a and II b trials and has been the key efficacy parameter discussed in the product labelling of several recently approved medicines in the US for pain. The dose range employed in the studies is 3 – 10 sprays per day.
The Phase III programme follows the announcement earlier this year of positive data from a Phase II b trial. Since this time, GW and Otsuka have met with the Food & Drug Administration (FDA) at an “end of Phase II” clinical meeting to review the Phase II clinical data and the Phase III trial design. GW and Otsuka are also currently engaged in discussions with the FDA regarding other aspects of the development plan.
Each of the Phase III trials is expected to recruit patients in Europe, North America, Latin America and Asia. The first Phase III trial site has now been initiated in Europe and the first patient is expected to be recruited during December 2010. The principal investigator of the first study is Dr. Russell K. Portenoy, Chairman of the Department of Pain Medicine and Palliative Care at Beth Israel Medical Centre in New York City. The second Phase III study is expected to commence in mid 2011.
The Phase II b trial evaluated three dose ranges of Sativex – a low dose (1-4 sprays per day), mid dose (6-10 sprays per day), and high dose (11-16 sprays per day) over a 5 week treatment period. In this study, the continuous response analysis showed statistically significant results in favour of Sativex for both the Sativex low and mid dose groups versus placebo (p=0.008 and p=0.038, respectively). The low and mid dose Sativex groups, when combined, were also significantly superior to placebo for the primary outcome measure (p=0.006) and for the important secondary efficacy measure of reduction in sleep disruption (p=0.016).
The results of this Phase II b dose ranging study were consistent with a previous Phase II a, 3-week clinical trial in 177 patients. In this prior study, Sativex showed a statistically significant improvement versus placebo in the continuous response analysis of improvement in average daily pain (p=0.044).
Dr. Stephen Wright, GW’s R&D Director, said, “We are pleased to have arrived at this important milestone in the development of Sativex for cancer pain. It aims to address the needs of the many patients with advanced cancer who do not attain adequate pain relief from an opioid regimen. We have completed two large Phase II trials with positive results and look forward to working with Otsuka on this comprehensive Phase III programme for Sativex in this important indication.”
Sativex is approved in the UK, Spain, Canada and New Zealand as a treatment for Multiple Sclerosis (MS) spasticity and GW aims to seek approval for Sativex in this MS indication across Europe and other selected markets. Cancer pain represents the initial target indication for Sativex in the US. It is intended that the Phase III cancer pain data will also be used by GW for future regulatory applications in this indication in Europe and around the world.