Products

Lead Program- APF530

CINV Background

Prevention and control of nausea and vomiting, or emesis, are paramount in the treatment of cancer patients. The majority of patients receiving chemotherapy will experience some degree of emesis if not prevented with an antiemetic. Chemotherapy treatments can be moderately emetogenic, meaning that
30-90% of patients experience CINV, or highly emetogenic, meaning that over 90% of patients experience CINV, if left untreated. Acute onset CINV occurs within the first 24 hours following chemotherapy treatment, with the highest risk period occurring within the first four hours. Delayed onset CINV occurs more than 24 hours after treatment and may persist for several days. Prevention of CINV is significant because the distress caused by CINV can severely disrupt patient quality of life and can lead some patients to discontinue chemotherapy. The unmet need is greatest with patients receiving highly emetogenic chemotherapy, particularly delayed onset CINV.

Current Therapy

Vomiting is a protective reflex against ingestion of what the body perceives to be potentially harmful substances, including some chemotherapeutic agents. These chemotherapeutic agents activate or destroy cells in the lining of the gut, releasing a neurotransmitter called serotonin. When serotonin binds to the 5-hydroxytryptamine type 3 (5-HT3) receptors, the patient experiences nausea and vomiting. By blocking the 5-HT3 receptors, granisetron and the other 5-HT3 antagonists prevent serotonin from binding to the
5-HT3 receptors, thereby inhibiting the vomiting reflex. Physicians may combine these 5-HT3 antagonists with other agents, such as corticosteroids or neurokinin-1 (NK1) antagonists, to better prevent CINV.

Current treatment options for CINV include 5-HT3 antagonists such as palonosetron (Aloxi®), ondansetron (Zofran®), dolasetron (Anzemet®) and granisetron (Kytril®), as well as aprepitant (Emend®), an NK1 antagonist, which is always used in combination with a 5-HT3  antagonist. As shown in the table below, all of the 5-HT3 antagonists are approved for the prevention of acute onset CINV in patients receiving either moderately or highly emetogenic chemotherapy. Only palonosetron is approved for the prevention of delayed onset CINV in patients receiving moderately emetogenic chemotherapy. No 5-HT3 antagonist is approved for the prevention of delayed onset CINV in patients receiving highly emetogenic chemotherapy.

Despite evidence that delayed onset CINV affects as many as 50–70% of patients, and that more patients experience delayed onset CINV than acute onset CINV, oncology nurses and physicians are likely to underestimate the magnitude of these problems in the patients for whom they care. This may occur in part since patients often do not report side effects they experience at home following chemotherapy treatments. Even though high percentages of chemotherapy patients experience such delayed nausea and emesis, presently palonosetron is the only 5-HT3 antagonist approved for dealing with this delayed onset CINV. We believe that our APF530, if approved, could become the second long-acting product given in a single administration that is capable of dealing with this important medical need.

Our Solution - APF530

The Company’s lead product, APF530, is being developed for the prevention of CINV in patients receiving either moderately or highly emetogenic chemotherapy. APF530 is delivered by a single subcutaneous injection and contains the 5-HT3 antagonist, granisetron. Granisetron, for infusion and oral tablets, is approved for the prevention of acute onset CINV, but not delayed onset CINV. We selected granisetron because it is a potent drug and the applicable granisetron patent expired in the United States on December 29, 2007.

Granisetron and other 5-HT3 antagonists, as a class, have become the most common antiemetic agents used in chemotherapy. However, no 5-HT3 antagonist formulation is currently approved for the prevention of both acute and delayed onset CINV for both moderately and highly emetogenic chemotherapy. A.P. Pharma's APF530 Phase 3 clinical trial demonstrated that it can deliver therapeutic levels of granisetron to prevent acute onset CINV for both moderately and highly emetogenic chemotherapy, and to prevent delayed onset CINV in moderately emetogenic chemotherapy. The sector efficacy data involving delayed onset CINV in highly emetogenic chemotherapy showed results for the higher dose of APF530 that were numerically better than palonosetron and statistically non-inferior, but did not achieve the statistically significant level of superiority necessary to support a claim in this sector. If A.P. Pharma obtains product approval for all uses except the delayed onset highly emetogenic one, the Company should have a product comparable to palonosetron, which despite the limitation of its claim for prevention of delayed onset CINV to only moderately emetogenic treatments, has achieved considerable commercial success.

In May 2009, A.P. Pharma submitted an NDA for APF530 under section 505(b)(2) of the Federal Food, Drug and Cosmetic Act, whereby the Company can rely upon the FDA's prior safety and efficacy findings for APF530's active ingredient, granisetron.  The FDA has accepted for review the NDA and, based on the Prescription Drug User Fee Act (PDUFA), has issued an action date of March 18, 2010.   

Other Programs

In addition to the Company’s lead program, A.P. Pharma has a pipeline of other product candidates using our Biochronomer technology.

APF112

APF112 utilizes A.P. Pharma’s Biochronomer delivery technology to target post-surgical pain relief. The product is designed to provide up to 36 hours of localized pain relief by delivering mepivacaine directly to the surgical site. Mepivacaine is a well-known, short-acting local anesthetic with an excellent safety profile. APF112 is designed to prolong the anesthetic effect of mepivacaine and thus minimize or eliminate the use of opiates. Opiates are currently used in the majority of surgical procedures as a means of managing post-operative pain, and while they are powerful and useful drugs, they may have side effects such as addiction, nausea, disorientation, sedation, constipation, vomiting, urinary retention and, in some situations, life-threatening respiratory depression. If efficacy in treating post-surgical pain can be demonstrated, A.P. Pharma believes that there will be substantial potential for this product, as there are approximately 20 million surgical procedures performed annually in the United States for which the product could potentially be utilized.

APF580

APF580 incorporates an opiate into A.P. Pharma’s Biochronomer technology and is designed to provide analgesia lasting at least seven days from a single injection. It is targeted for situations where the intensity and duration of pain require use of an opiate rather than a local anesthetic. APF580 may find use in acute and chronic pain settings, improve patient compliance and reduce the risk of drug abuse. The Company’s initial animal pharmacokinetic studies, completed in 2006, present a promising profile, supporting future product development for post-surgical (inpatient) and chronic pain applications (cancer pain). In September 2008, A.P. Pharma filed an IND for APF580 with the FDA. In addition, the Company is working with Merial, a major animal health care company, that is developing a variant of APF580 for use in cats and dogs.