Acacia Pharma Announces Excellent Phase II Results for APD421 in Post-Operative Nausea & Vomiting (PONV)

CAMBRIDGE, England, May 28, 2012 /PRNewswire/ --

Acacia Pharma announces positive results from its Phase II study of APD421, in the prevention of post-operative nausea & vomiting (PONV). The study showed that APD421 significantly reduced the incidence of nausea and vomiting compared to placebo in adult surgical patients at moderate-to-high risk of suffering PONV. Vomiting and especially nausea remain a major problem for patients after surgical operations, despite the availability of a number of approved anti-emetics.

APD421 comprises a completely new, patent-protected use of a currently marketed dopamine D₂/D₃ antagonist for the prevention and treatment of PONV.

The double-blind, Phase II study, comparing three doses of APD421 with placebo, was conducted in ten major centres in France, Germany and the USA, and recruited 223 surgical patients with two or more of the four established "Apfel" risk factors for PONV. The primary endpoint was protection against PONV, defined as no vomiting or retching and no requirement for anti-emetic rescue medication in the first 24 hours after surgery. APD421 was highly significantly superior to placebo at preventing PONV, the optimal dose approximately halving the PONV rate, from 67% in the placebo group to 36% (p=0.004). The incidence and severity of nausea were also significantly reduced.

APD421 was very well tolerated at all three dose levels, with no significant difference in the frequency of any adverse event for any dose of APD421 compared to placebo, and no serious adverse reactions. No prolongation of the QT interval was seen with APD421 nor was there any evidence of sedation, psychological symptoms, extrapyramidal toxicity or gastrointestinal disturbance, a clear advantage over many other anti-emetics.

Acacia Pharma's CEO, Dr Julian Gilbert, commented: "We are delighted with these excellent results. Anaesthetists seek a safe dopamine antagonist for the prevention and treatment of PONV and APD421 appears to meet this profile. We therefore believe that it has the potential to become a mainstay of anti-emetic therapy and contribute greatly to the well-being of patients undergoing surgery."

Dr Gabriel Fox, Acacia Pharma's Chief Medical Officer, added: "This was a robust, well-conducted trial in leading European and US centres and has shown an unequivocal benefit for APD421 in patients who are the hardest to protect from post-operative sickness, those with multiple Apfel risk factors."

About Acacia Pharma

Acacia Pharma (http://www.acaciapharma.com) is a pharmaceutical company focused on cancer supportive care, a rapidly developing commercial opportunity. The growth in the cancer supportive care market has been driven by the increasing incidence of cancer, the expansion of effective cancer therapies and the desire to improve both the effectiveness of treatment and the quality of life of cancer patients.

Acacia Pharma has generated a pipeline of product opportunities addressing a range of supportive care indications such as nausea & vomiting, xerostomia (dry mouth) and cachexia (muscle wasting) using a commercially driven approach to product discovery based on known drugs. This strategy leads to product opportunities with a higher probability of success and enables rapid clinical proof-of concept. In addition, Acacia Pharma's products are expected to reach the market quickly given that they are based on the novel use of well-characterised pharmaceuticals.

Acacia Pharma is led by an experienced management team who have already successfully built and exited a number of life sciences companies. Management, Gilde Healthcare and Lundbeckfond Ventures are the Company's key shareholders. Acacia Pharma is based in Cambridge, UK.

About post-operative nausea & vomiting (PONV)

PONV offers Acacia Pharma a rapid, low risk, high value development opportunity for APD421 due to the acute nature of the condition, the large number of surgical procedures and the well-documented, benign, safety profile of the active ingredient. More than 130 million surgical procedures are performed worldwide each year, with PONV occurring in approximately 35% of all patients and in 70% of those classed as high risk.

The four established "Apfel" risk factors for PONV are female sex, non-smoking status, prior history of PONV or motion sickness and use of opioid analgesia in the post-operative period. A patient with all four risk factors is estimated to have an 80% risk of suffering PONV in the absence of effective prophylaxis. The nature and length of surgery and use of volatile anaesthetics may also add to an individual's risk. PONV most commonly starts in the first three hours after the end of anaesthesia, with a decreasing trend over 24 hours.

PONV is a significant issue for patients and healthcare providers. It is rated second only to pain as the complication most feared by patients and contributes significantly to anxiety and patient distress. PONV can also delay discharge or result in readmission after in-patient procedures; and can require admission for day-case patients. This has a significant economic and social impact.

PONV is typically managed using a multimodal prophylactic approach, including the frequent use of combination drug therapy, especially in high-risk patients. Most surgical units have a standard protocol for prophylaxis of moderate and high-risk patients, usually involving intravenous (IV) administration of one or more anti-emetics before or during the anaesthetic procedure.

There are a number of approved agents in use, and commonly prescribed drugs include 5HT₃-antagonists such as ondansetron and granisetron, mixed activity agents such as metoclopramide and the corticosteroid dexamethasone. Until recently the preferred agent of anaesthetists was the dopamine antagonist droperidol. It has, however, fallen into disuse in many key markets due to cardiovascular and psychological safety concerns; the drug has a black box warning in the USA. There is therefore a significant unmet need for new agents with different mechanisms of action and in particular for the provision of a safe dopamine antagonist.

Despite the anti-emetics in common use, many patients still suffer post-operatively with vomiting and especially nausea. About a third of those given prophylaxis for PONV require rescue therapy in the first six hours after surgery, representing a substantial commercial opportunity.

About APD421

APD421 contains a potent dopamine D₂ and D₃-receptor antagonist, currently marketed for the treatment of certain psychiatric disorders, which Acacia Pharma has repurposed for the completely new use of prevention and treatment of post-operative nausea & vomiting (PONV). The active ingredient in APD421 has been approved for more than 25 years and has established a highly favourable safety profile, even with chronic use at high doses. It is available as an oral tablet, oral solution and intramuscular injection. APD421 has been formulated in an intravenous injection, which is the preferred route of administration for the management of PONV. APD421 is given acutely at very low doses.

The same active ingredient is also being developed by Acacia Pharma as APD403 for the prevention of chemotherapy-induced nausea & vomiting (CINV). The drug is at present under investigation in cancer patients receiving the highly emetogenic chemotherapy agent cisplatin. The results from this study are anticipated at the end of June 2012.