Acacia Pharma has announced positive results from its Phase IIa proof-of-concept study investigating APD403 for the prevention of acute nausea & vomiting in cancer patients receiving the highly emetogenic chemotherapy drug cisplatin.
Although a number of anti-emetics are available on the market, these are generally much better at controlling vomiting than nausea.
Therefore, nausea remains the major unmet medical need for cancer patients receiving cisplatin, and many other kinds of chemotherapy.
The study, exploring the efficacy of APD403 alone and in combination with ondansetron, a 5-HT3-antagonist approved for prevention and treatment of CINV, took place in four hospitals in Denmark and the UK.
Fifty-one patients were enrolled into four cohorts, three treated with different doses of single-agent APD403 and the fourth treated with the combination of APD403 and a standard dose of intravenous ondansetron.
The primary endpoint was complete response, defined as no vomiting and no requirement for anti-emetic rescue medication during the first 24 hours after dosing with cisplatin. Secondary endpoints included incidence and severity of nausea as well as safety.
In the initial exploratory cohorts, single agent APD403 showed encouraging benefit, especially in controlling nausea. When APD403 was combined with a standard dose of intravenous ondansetron, a complete response in 19 out of 23 patients (83%) was achieved, substantially higher than the 50% rate which would be expected with ondansetron alone.
Most promisingly, the response rate of this two drug combination is comparable to the standard of care regimen of three anti-emetics currently recommended by international experts therefore offering potential safety and compliance advantages.
Nausea was rarely reported (measured on a 100 mm visual analogue scale (VAS), where 0 is no nausea and 100 is the worst nausea possible).
Only 2 of the 23 patients receiving the combination spontaneously reported significant nausea requiring rescue anti-emetic medication.
Nausea scores were also collected prospectively 4 times during the 24-hour observation period and only 2 out of 91 VAS measurements were above 5 mm. No clinically significant side effects were seen in the study.
Dr Julian Gilbert, Acacia Pharma’s CEO said, “APD403 appears to be a safe and powerful anti-sickness drug, capable of virtually wiping out nausea in cancer patients receiving cisplatin. This is extremely encouraging as controlling nausea is now the main priority in the management of CINV.”
Acacia Pharma’s CMO, Dr Gabriel Fox, added, “The efficacy seen with APD403 in combination with ondansetron is exceptional and appears to match the triple combination of ondansetron, aprepitant and dexamethasone recommended for preventing CINV induced by cisplatin. This could give physicians a chance to simplify the management of these patients and significantly reduce unwanted side effects.”
APD403 comprises a completely new, patent protected use of a currently marketed dopamine D2/D3 antagonist for the prevention and treatment of chemotherapy induced nausea & vomiting (CINV).
The same active ingredient is also being developed by Acacia Pharma as APD421 for the prevention of post-operative nausea & vomiting (PONV).