Acacia Pharma Group, the supportive care company developing products for US and international markets, announces positive results from a Phase III study investigating BAREMSIS (amisulpride injection, formerly APD421) in combination with standard antiemetics for the prevention of post-operative nausea and vomiting (PONV) in high-risk patients.
Dr Julian Gilbert, Acacia Pharma’s CEO, commented: “There is a compelling medical and commercial need for a safe and effective dopamine antagonist antiemetic that can be used in combination with current standard-of-care to manage PONV. The results from this study show that BAREMSIS could be used in the prevention of PONV in high-risk patients. Very pleasingly, the magnitude of BAREMSIS’ effect, a relative risk reduction of 22%, was consistent with the results seen in our monotherapy prophylaxis trials and, most importantly, with that routinely seen with the current standard-of-care drugs such as ondansetron.”
He added: “We have now completed the prophylaxis efficacy studies for BAREMSIS and the first of two treatment studies is well under way. Our aim is to receive an approval for the use of BAREMSIS in both the treatment and prophylaxis of PONV, alone and in combination. We anticipate submitting our NDA to the FDA in the second half of 2016.”
The Phase III combination trial compared the prophylactic use of BAREMSIS plus a standard antiemetic (for example ondansetron or dexamethasone) against a placebo plus a standard antiemetic. The primary endpoint was complete response, defined as no vomiting or retching and no requirement for antiemetic rescue medication in the first 24 hours after surgery.
The study was one of the largest PONV studies ever undertaken and was conducted at multiple sites in Europe and the US. It recruited a total of 1204 surgical patients with 3 or 4 risk factors for PONV (the Apfel risk factors), of whom 1147 were evaluable.
BAREMSIS significantly improved the complete response rate when added on top of a standard antiemetic compared to placebo and a standard antiemetic (57.7% vs 46.6%, p=0.0002). In addition, all secondary efficacy endpoints, including the rate of vomiting, nausea and use of rescue medication, were also met. The safety profile of BAREMSIS was excellent. No toxicities of note were seen and the profile of adverse events and laboratory abnormalities was as good as placebo. Detailed data will be presented in due course at relevant scientific meetings and submitted for publication in a peer-reviewed journal.
International consensus guidelines recommend the use of combinations of antiemetics from different mechanistic classes for the prevention of PONV in high-risk patients acknowledging the multiple biological pathways that are implicated in PONV. Currently two classes of antiemetics are predominantly used to prevent PONV in these patients, 5HT3 antagonists (usually ondansetron) and corticosteroids (usually dexamethasone). However, a safe and effective third mechanism antiemetic is required and BAREMSIS, as a dopamine antagonist, could fulfil this need.