CAMBRIDGE, England, February 13, 2017 /PRNewswire/ --
Extensive Phase 3 programme demonstrates clinical potential of BAREMSIS in rescue treatment and prophylaxis of PONV - NDA to be submitted to the US FDA 1H 2017
Acacia Pharma Group Ltd ("Acacia Pharma"), the supportive care company developing products for US and international markets, announces positive results from its fourth and final pivotal Phase 3 study investigating BAREMSIS™ (amisulpride injection, formerly APD421) for the rescue treatment of patients who develop post-operative nausea & vomiting (PONV), despite having received prior antiemetic prophylaxis.
Dr Julian Gilbert, Acacia Pharma's CEO commented: "We are delighted with these results demonstrating that BAREMSIS is safe and effective at rescuing patients who suffer PONV despite having received prior prophylaxis with standard anti-emetics. No other anti-emetic has a specific label for treating this significant unmet need and we intend to position BAREMSIS as the drug of choice for treating the 30-40% of surgical patients who suffer PONV despite prior prophylaxis, as well as for combination prophylaxis in high-risk patients."
Acacia Pharma has now completed four pivotal Phase 3 studies of BAREMSIS successfully, all meeting their primary endpoint, and these will form the basis of the efficacy and safety package which the Company aims to submit to the US FDA as part of its New Drug Application (NDA) in 1H 2017. The Company will seek a broad and unique approval for BAREMSIS for the rescue treatment and prophylaxis of PONV, alone and in combination.
PONV is distressing, can have a detrimental impact on surgical outcomes and significantly impede the post-operative recovery process. It can delay hospital discharge, lead to unanticipated readmissions increasing healthcare costs and give the patient a poor surgical experience. Better management of PONV can therefore decrease hospital costs and improve patient outcomes and satisfaction scores.
Surgical patients at moderate or high risk of PONV are given prophylactic antiemetics prior to surgery, with standard-of-care based upon 5HT3 antagonists and corticosteroids. However, up to 40% of these patients develop PONV and must be treated with an antiemetic from a different mechanistic class. BAREMSIS is a dopamine antagonist antiemetic and offers anaesthetists a drug that is able to fulfil this important unmet medical need and better manage PONV.
The Phase 3 rescue treatment trial compared two doses of BAREMSIS, a novel dopamine D2/D3 antagonist antiemetic, against placebo in patients with established nausea and/or vomiting after surgery, who had previously received prophylactic antiemetics. The double-blind study, the first ever major study to investigate rescue with a different class of antiemetic, took place in leading institutions in the USA, Canada, France and Germany and recruited 2,285 patients, of whom 705 (31%) went on to experience PONV and were randomised into the trial. The primary endpoint was the successful resolution of the episode of PONV (no recurrence of vomiting or requirement for further antiemetic rescue) in the 24-hour period after rescue treatment, termed a complete response. The optimum dose of BAREMSIS significantly improved the complete response rate when compared to placebo (p=0.003); the magnitude of effect was consistent with the Company's previous Phase 3 trial results. Detailed data will be presented in due course at relevant scientific meetings and submitted for publication in a peer-reviewed journal.
NOTES TO EDITORS
About Acacia Pharma
Acacia Pharma is developing supportive care product opportunities for post-surgical 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, by 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 lead project, BAREMSIS for post-operative nausea & vomiting (PONV), has generated positive results in Phase 3 clinical studies and it is aimed to submit regulatory submissions from 1H 2017. Its sister project, APD403 for chemotherapy induced nausea & vomiting (CINV) has successfully completed one Phase 2 dose-ranging study in patients receiving highly emetogenic chemotherapy. 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. Management, Gilde Healthcare, Lundbeckfonden Ventures, Novo A/S and F-Prime Capital are the Company's key shareholders. Acacia Pharma is based in Cambridge, UK and has US operations in Indianapolis, IN. www.acaciapharma.com
BAREMSIS (formerly APD421) comprises a low dose intravenous formulation of the marketed dopamine antagonist amisulpride, which Acacia Pharma has repurposed for the completely new, patent-protected use of management of PONV. Amisulpride is currently indicated for the management of psychoses, and is given at high doses in oral form. Amisulpride is not available for any use in the US.
Data generated by Acacia Pharma indicate that BAREMSIS is an effective, safe, dopamine antagonist that can prevent and treat PONV alone and in combination. The company believes that a drug with these characteristics can be particularly useful
- rescuing patients who develop PONV despite having received prior PONV prophylaxis with standard of care (5HT3 antagonist and corticosteroids, alone or in combination), and
- prophylactically to prevent PONV in combination with standard of care (5HT3 antagonists and/or corticosteroids) in the highest risk patients.
Post-operative nausea & vomiting (PONV) is a common complication of surgery which is distressing to patients and increases healthcare costs. In untreated patients, the incidence of vomiting is ~30%, the incidence of nausea is ~50% and the PONV rate in high-risk surgical patients is up to 80%. PONV is reported by patients as one of the most troublesome of all post-operative complications.
PONV can lead to prolonged discharge times and unanticipated hospital admissions (increasing healthcare costs) and to the possibility of reduced healthcare provider income as a consequence of Medicare's Hospital Readmissions Reduction Program and the pay-for- performance payment system in the Hospital Value-Based Purchasing (VBP) Program, in the US. The objective of PONV management, therefore, is to decrease the incidence of PONV, reducing patients' length of stay in the hospital, particularly the post-anaesthesia care unit (PACU), and avoiding hospital readmission, thereby reducing healthcare costs; and reducing patient distress, improving overall satisfaction, thereby optimising provider income through improved patient outcomes.
PONV risk factors
A simplified risk scoring system has been developed by Apfel et al to assess the risk of PONV in surgical patients. The four "Apfel risk factors" are:
- Being female
- Being a non-smoker
- Having a prior history of PONV or motion sickness
- An expected use of post-operative opioid analgesia.
Each of these four risk factors independently contributes around 20% risk of PONV. Patients with two "Apfel risk factors" are considered at moderate risk of PONV, while those with three or four are considered at high risk. A patient with all four risk factors has up to an 80% chance of PONV in the absence of effective prophylaxis.
Guidelines for the management of PONV
It is recommended that surgical patients are prescribed prophylactic antiemetics alone or in combination, according to their risk of PONV. Those considered at moderate risk of PONV should be given at least one prophylactic antiemetic and those at high risk of PONV, should be given multiple antiemetics of different mechanisms of action to optimise efficacy.
It is recommended that when a patient who has received antiemetic prophylaxis suffers PONV, an antiemetic from a different mechanism of action to that given prophylactically, is used to provide rescue treatment. Repeating the mechanism given prophylactically confers no additional benefit.
Current management of PONV
Two classes of drugs are predominantly used for the management of PONV: 5HT3 antagonists (eg ondansetron); and corticosteroids (eg dexamethasone). Ondansetron and dexamethasone have been investigated in many clinical studies and generally deliver a relative risk reduction (RRR) in the incidence of PONV of 15-30%,,.
The majority of surgical patients receiving prophylaxis are given a 5HT3 antagonist alone or in combination with a corticosteroid. However, Acacia Pharma believes that drug choices are limited in the highest risk patients where a third antiemetic of a different mechanism is required.
Up to 40% of patients experience PONV, requiring rescue medication, despite the routine use of prophylactic antiemetics. The majority of surgical patients have been given a prophylactic 5HT3 antagonist therefore precluding their use for rescue. Dexamethasone (a corticosteroid) has a slow onset of action and is not recommended for rescue. Therefore Acacia Pharma believes antiemetic choices for rescue are extremely limited.
Unmet need for a dopamine antagonist for PONV
Droperidol (a dopamine antagonist) was previously considered the drug of choice for PONV management until it received a boxed warning for QT-interval prolongation. A boxed warning is the most serious form of warning issued by the U.S. Food and Drug Administration for prescription drug products. The boxed warning and concerns about its side effect profile (particularly extra pyramidal movement disorders and sedation) have severely limited the use of droperidol as an antiemetic.
Therefore there is currently no safe, effective, dopamine antagonist antiemetic available for anaesthetists to:
- Rescue patients having previously been given prophylaxis with a 5HT3 antagonist (alone or in combination).
- Add to the most prevalent prophylactic regimen of a 5HT3 antagonist plus a corticosteroid, in the highest risk patients.
Dr Julian Gilbert
Citigate Dewe Rogerson
Dr Mark Swallow
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SOURCE Acacia Pharma