Acacia Pharma Announces Positive Results From Phase Iia Nausea & Vomiting Study in Cancer Patients
Cambridge, UK – 1st October 2012: Acacia Pharma, a pharmaceutical company specialising in the development of drugs for cancer supportive care, announces 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).
Dr Julian Gilbert
Telephone: +44 (0)1223 875130
Citigate Dewe Rogerson
Dr Mark Swallow
Telephone: +44 (0) 20 7638 9571
About Acacia Pharma
Acacia Pharma (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 chemotherapy induced nausea & vomiting (CINV)
Chemotherapy induced nausea & vomiting (CINV) occurs in approximately 70% of all cancer patients receiving chemotherapy; in 90% of those receiving highly emetogenic chemotherapy and in 30-90% of those receiving moderately emetogenic chemotherapy. It is a considerable concern for patients and is one of the major side effects of cancer therapy. The effects of CINV can be more distressing to a patient than future concerns of life expectancy, sometimes resulting in the patient choosing to discontinue potentially curative therapy.
There are two major types of nausea & vomiting associated with chemotherapy: acute CINV, which occurs on the day of treatment and lasts up to 24 hours and delayed CINV which occurs up to five days following chemotherapy.
The most important risk factor for CINV is the emetogenic potential of the particular chemotherapy being used. Treatment is classified into mildly emetogenic (eg fluorouracil, etoposide, low dose methotrexate, vinca alkaloids), moderately emetogenic (eg doxorubicin, low dose cyclophosphamide, mitoxantrone, high dose methotrexate) and highly emetogenic (eg cisplatin, dacarbazine, high dose cyclophosphamide).
There are a number of approved agents in use, and commonly prescribed drugs include 5HT3-antagonists such as ondansetron, granisetron and palonosetron. These are usually used in combination with the steroid dexamethasone. In addition, the NK-1 inhibitor aprepitant can be added to this regimen to improve outcomes further. Doses of anti-emetics for CINV are often higher than those used in PONV due to the severity of the emetogenic stimulus.
Despite the improvements in treating CINV there remain a number of clear unmet needs. In particular, there is a significant requirement to reduce the incidence of nausea. The regimens described above are relatively effective at stopping a patient being sick (vomiting) but much less so at stopping the patient feeling sick (nausea), which is often the most distressing symptom they face.
APD403 contains a potent dopamine D2/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 chemotherapy induced nausea & vomiting (CINV). The active ingredient in APD403 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. APD403 will be available as an intravenous injection to treat acute CINV and a low dose tablet for delayed CINV.
The same active ingredient is also being developed by Acacia Pharma as APD421 for the prevention of post-operative nausea & vomiting (PONV). APD421 has just completed a 223 Phase II dose ranging study in which it was shown to be extremely effective in preventing PONV. Click here for more information.
Mark Swallow, Ph.D.
Citigate Dewe Rogerson
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Posted: October 2012