Acacia Pharma Announces Positive Results From Phase 2 Study With APD403 in Chemotherapy Induced Nausea & Vomiting (CINV)

CAMBRIDGE, England, May 6, 2015 /PRNewswire/ --

- Primary Endpoint of Preventing Delayed CINV Met With High Significance 

Acacia Pharma Ltd ("Acacia Pharma" or "the Company"), a specialty pharmaceutical company developing supportive care products for post-surgical and cancer patients in the US and international markets, announces positive results from its Phase 2 study of APD403 in the prevention of chemotherapy-induced nausea & vomiting (CINV).

CINV occurs in approximately 70% of all cancer patients receiving chemotherapy and in 90% of those receiving highly emetogenic chemotherapy (HEC). It is one of the most significant and feared side effects of cancer therapy and a major concern for patients and caregivers. CINV occurs in two phases: the acute phase occurring in the first 24 hours after chemotherapy; and the delayed phase, lasting for a further four days. Despite significant improvements in managing the condition and the availability of a range of anti-emetics, there remains a clear unmet need to reduce the incidence of CINV, in particular the occurrence of nausea in the delayed phase.

The randomised, double blind, Phase 2 study was conducted in 342 cancer patients receiving HEC (either high-dose cisplatin, or cyclophosphamide and an anthracycline for breast cancer). The trial compared 3 doses of APD403 against placebo in the delayed phase of CINV. All patients received the same acute-phase anti-emetic prophylaxis.

The primary endpoint was complete response (no vomiting or retching and no requirement for anti-emetic rescue medication) in the period 24-120 hours after the administration of chemotherapy. APD403 was significantly superior to placebo at preventing delayed CINV, with the optimal dose improving the complete response rate by 26% (p=0.002) and significantly (p<0.05) reducing the incidence of both nausea and vomiting, compared to placebo. Complete response in the overall phase (0-120 hours) was also significantly improved (p=0.015). The safety profile was excellent, with fewer adverse events reported in each of the APD403 arms than in the placebo arm. Detailed data from this study will be presented at an upcoming scientific meeting and submitted for publication in a peer-reviewed journal.

Acacia Pharma's CEO, Dr Julian Gilbert, commented: "We are delighted with these results. Oncologists seek a product with an alternative mechanism of action that can be added to current anti-emetic regimens to better manage CINV and, in particular, improve the delayed phase response. Based on these impressive data, APD403 appears to meet this profile. We believe that APD403 has the potential to become a mainstay of CINV management and to contribute greatly to the well-being of cancer patients. We look forward to confirming these results in Phase 3 trials and providing physicians and patients with a new and effective mechanism for managing CINV."

APD403 is a novel and proprietary product containing the dopamine antagonist amisulpride, which Acacia Pharma is also developing as APD421 for the prevention and treatment of post-operative nausea & vomiting (PONV).

About Acacia Pharma 

Acacia Pharma is developing supportive care product opportunities for post-operative and cancer patients. Patients and healthcare professionals urgently need new and improved interventions in these rapidly expanding, yet poorly served, areas of supportive care, to improve treatment outcomes and patients' quality of life.

Acacia Pharma has generated its pipeline of product opportunities using a commercially driven approach to product discovery identifying completely new uses for marketed drugs, a process termed repurposing. This strategy leads to opportunities with a higher probability of success and enables more rapid development. All of Acacia Pharma's repurposed programmes are optimised for their new use using a new route of delivery and dose that are appropriate for the new indication identified, thereby differentiating them from the original marketed product.

The company's lead project, APD421 for post-operative nausea & vomiting (PONV), has generated positive results in Phase 3 clinical studies. Its sister project, APD403 for chemotherapy induced nausea & vomiting (CINV) has successfully completed a Phase 2 dose-ranging study. In addition, the company has completed a Phase 2 study with APD515 for xerostomia (dry mouth) in advanced cancer patients and a Phase 2a study with APD209 for cancer cachexia (muscle wasting).

Acacia Pharma is led by an experienced management team, members of which have successfully built and exited life sciences companies. Management, Gilde Healthcare, Lundbeckfond Ventures, Novo A/S and Fidelity Biosciences are the Company's key shareholders. Acacia Pharma is based in Cambridge, UK. http://www.acaciapharma.com 

About CINV 

Chemotherapy-induced nausea & vomiting (CINV) is common side effect of cancer chemotherapy. The incidence of CINV varies with the type of chemotherapy, dose, the route of administration and patient-specific factors. The incidence of CINV in patients receiving highly emetogenic chemotherapy (HEC) is over 90% while in those receiving moderately emetogenic chemotherapy (MEC) it is between 30 and 90%. Nausea and vomiting can occur on the day of chemotherapy administration (acute CINV) and can persist for two to five days after the administration of chemotherapy (delayed CINV). CINV has a significant effect on quality of life and can compromise patient health. Severe CINV may necessitate a delay or reduction in chemotherapy and can ultimately lead to treatment withdrawal. The goal of CINV management is the prevention, rather than treatment, of symptoms.

The worldwide therapeutic guidelines for the management of CINV, recommend the use of "triple therapy" comprising a 5HT₃ antagonist (e.g. ondansetron), a corticosteroid (e.g. dexamethasone) and an NK-1 antagonist (e.g. aprepitant) in patients receiving HEC. The guidelines recommend the use of a 5HT₃ antagonist and a corticosteroid in combination for patients receiving MEC (Roila et al 2010). The use of triple therapy prophylaxis can produce a complete response rate (no vomiting and no rescue medication) in acute CINV of up to 85% of patients receiving HEC. However, this complete response rate reduces down to as low as 50% in the delayed CINV (Warr et al 2005), with failures being driven primarily by nausea. The management of nausea in the delayed phase of CINV is considered to be the major unmet medical need.

About APD403 

APD403 comprises the dopamine antagonist amisulpride, which Acacia Pharma has repurposed for the completely new, patent-protected use of management of CINV. Amisulpride is currently indicated for the management of psychoses. Amisulpride is not available in any form, for any use, in the US.

Data generated by Acacia Pharma suggest that APD403 is an effective, safe, dopamine antagonist antiemetic. The company believes that a drug with the characteristics described in this release could be added to current CINV regimens to improved delayed CINV response rates.

Amisulpride is also being developed by Acacia Pharma as APD421 for the prevention of post-operative nausea & vomiting (PONV).