APPA's chemotherapy-induced nausea drug FDA decision is days away |
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| By Chris Fields, Special Report Correspondent |
| Tuesday, 02 March 2010 09:21 |
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Let's look at the facts: In May 2009 APPA submitted their new drug application (“NDA”) for approval of APF530 to the U.S. Food and Drug Administration (“FDA”). The NDA was accepted for review by the FDA in July 2009 and based on the Prescription Drug User Fee Act (“PDUFA”), the FDA has issued an action date of March 18, 2010. I feel approval for granisetron looks very likely on March 18th. The question is whether they get approval for both acute & delayed onset for the prevention of chemotherapy-induced nausea and vomiting (CINV)-- only being the second therapy other than palonosetron to claim those multiple indications A.P. Pharma is a specialy pharmaceutical company developing products using its proprietary biochronomer polymer-based drug delivery technology. The company’s primary focus is on its lead product candidate, APF530, which has completed a pivotal Phase 3 clinical trial for the prevention of CINV. The company has additional clinical and preclinical stage programs in the area of pain management , all of which utilize its bioerodible injectable and implantable delivery systems. The company has two other products in clinical development currently. Those products are APF112 for Post-surgical pain relief (Mepivacaine) which is currently in Phase II and APF580 for pain relief (Undisclosed Opiate) which just filed an IND. The Company’s lead product, APF530, is being developed for the prevention of Chemotherapy-Induced Nausea And Vomiting (CINV) in patients receiving either moderately or highly emetogenic chemotherapy. APF530 is delivered by a single subcutaneous injection and in it has 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. Granisetron was selected by A.P. Pharma because it is a potent drug and the applicable granisetron patent expired in the United States on December 29, 2007. There are high percentages of patients on chemotherapy who experience delayed nausea and emesis, currently Palonosetron is the only 5-HT3 antagonist approved for dealing with this delayed onset CINV. A.P. Pharma believes that if APF530 is approved, that it could become the second long-acting product given in a single administration with the capacity to deal with this medical condition. The most utilized antiemetic agents used in chemotherapy are Granisetron and other 5-HT3 antagonists. The opportunity for A.P. Pharma is that there is currently no approved therapy for the prevention of both acute and delated onset CINV for both moderately and highly emetogenic therapy. The Phase III trial by A.P. Pharma demonstrated that it could deliver therapeutic levels of granisetron to prevent acute onset CINV in for both moderately and highly emetogenic chemotherapy, and to prevent delayed onset CINV in moderately emetogenic chemotherapy. The efficacy data that involved delayed onset CINV 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 that was needed to claim in this class of drugs. If A.P. Pharma does obtain product approval for all of the uses except for delayed onset highly emetogenic one, the Company should have a product comparable to palonosetron, which despite the limitation of delayed onset CINV has been widely and commercially successful. The company conducted a Phase 3 study of Sustained Released Granisetron (AP530) Compared to Palonosetron For The Prevention Of Chemotherapy-Induced Nausea And Vomiting (CINV) : http://phx.corporate-ir.net/External.File?item=UGFyZW50SUQ9NzM2NXxDaGlsZElEPS0xfFR5cGU9Mw==&t=1 Phase 3 results for APF-530 (complete response rates) - Acute Onset CINV with Moderately Emetogenic Chemo - APF-530 -- 76.9 % Aloxi ------- 75.0 % Acute Onset CINV with Highly Emetogenic Chemo - APF-530 -- 59.0 % Aloxi ------- 57.7 % Delayed Onset CINV with Moderately Emetogenic Chemo - APF-530 -- 81.3 % Aloxi ------- 80.7 % Delayed Onset CINV with Highly Emetogenic Chemo - APF-530 -- 68.3 % Aloxi ------- 66.4 % Based on A.P. Pharma’s discussions with the FDA, the Company filed its NDA in May 2009 under Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FDCA). Section 505(B)(2) of the FDCA permits the FDA, in its review of a NDA, to rely on previous FDA findings of safety and efficacy of the active ingredient in APF530, granisetron. The 505(b)(2) approval pathway is distinguished from the Abbreviated New Drug Application, or generics route, by the requirement that drug products approved under this section must have significant difference relative to the reference approved product. The additional information in the 505(b)(2) applications can be provided by literature or reference to past FDA findings of safety and efficacy for approved drugs, or it can be based upon studies conducted by or for the applicant to which it has obtained a right of reference. The majority of 505(b)(2) applications are filed for new formulations of currently approved drugs, so there is an existing understand-on the part of the FDA, as well as the medical community-of their safety and efficacy. We know that APPA met 3 of the 4 primary endpoints in their Phase III study. We also know that the only on that was not met was that for the superiority claim of APF530 in comparison to palonosetron for the prevention of delayed onset CINV following administration of highly emetogenic therapy. The FDA should grant FDA approval based on the clinical data in the acute setting. The question is why the FDA would require APF530 to prove clinical superiority to palonosetron in the delayed setting when the same is not required in the acute setting. Palonosetron (Aloxi) was approved in the delayed phase after showing superiority to granisetron in a large multi center randomized double-blind clinical trial (PROTECT Study) conducted in Japan. The company states on its website: “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. So basically, it does do what aloxi does currently---- 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.” The new formulation for APF530 lasts for 5 days vs. Aloxi’s 3 days. APF530 will be easier to administer than aloxi as it is administer subcutaneously (as a shot) vs intravenously . This is important for patients because of a preference for ease of administration and less frequently. This is important for insurance companies as well that have to pay more money as drugs are administered more frequently. Financially APPA has only 20m shares in the float and has 40 million shares outstanding. The inside ownership is very strong. APPA put into place a new management team in late 2008 and that management has been solid moving the company initiatives forward. Last October, one of APPA's directors, Kevin C. Tang, purchased 2,443,181 shares of his company (which put the total amount of shares he personally owns at 10,436,506). Other company insiders have also acquired additional shares of the company throughout last year. APPA has 44% of the float held by institutions and management. 20% of shares held by institutional and mutual fund owners. 53% of the shares are held by all insiders and 5% of owners. The top two institutional owners both have a low turnover rating. Here are some current ownership % of AP Pharma (shares and warrants of institutional ownership) - Tang Capital/Kevin Tang - 12.8 mil shares (31.3%) Baker Bros - 9.44 mil shares (22.53%) Boxer Capital - 2.92 mil shares (7.3%) Deerfield - 2.52 mil shares (6.39%) Orbimed - 1.84 mil shares (4.68%) APPA has about $2 million in cash. According to their own estimates, they should have enough cash to fund their operation through 2010. The company obtained 8.1 million dollars via a private placement deal last October. On January 11th of this year, A.P. Pharma received the last milestone payment of 2.5 million dollars from an affiliate of Paul Capital Healthcare. The payment became payable under the agreement that the company entered into on Oct. 1, 2005 to sell its royalty rights to Retin-A Micro and Carac to an affiliate of the Paul Royalty Fund. "We are delighted to receive this non-dilutive funding from Paul Capital Healthcare as we continue to pursue the approval of our first product, APF530, for the prevention of chemotherapy-induced nausea and vomiting in cancer patients," said Ronald Prentki, A.P. Pharma’s president and CEO. One would think the FDA would prefer that patients have a choice of more than one compound in both the acute and delayed settting but the FDA will make its decision on March 18th. Either way the company should see approval of Granisetron in either acute only or acute and delayed onset of CINV. No Positions BiomedReports is not paid or compensated to report news and developments about publicly traded companies. Full disclosure can be read in the About Us Section Add this page to your favorite Social Bookmarking websites            |
A closer look at March 18th's upcoming FDA decision for A.P. Pharma (Nasdaq: APPA), whose APF530 drug targets a $1 billion dollar market.
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