On October 22, 2012, Pozen (NASDAQ:POZN) presented a full analysis of the integrated results of the two Phase 3 studies comparing PA-325/40 (EC-ASA 325 mg + IR omeprazole 40 mg) to enteric-coated aspirin (EC-ASA) 325 mg in patients requiring aspirin (ASA) for secondary cardiovascular prophylaxis who were at risk for ASA-associated gastric ulceration. In the two Phase 3 trials, subjects were randomized to either PA-325/40 or EC-ASA 325 mg, taken once daily in the morning on an empty stomach, approximately 1 hour before breakfast. At baseline, subjects were required to be H. pylori stool-antigen negative and have no endoscopic ulcers. Subsequent endoscopies were performed at months 1, 3, and 6. Both trials were run under a special protocol assessment (SPA) with the U.S. Food and Drug Administration (FDA).
The primary endpoint of the study was cumulative proportion of subjects with endoscopically-confirmed gastric ulceration (defined as a mucosal break of at least 3 mm in diameter with depth) at any time throughout 6 months. Results below show an impressive separation for PA-325/40 vs. EC-ASA:
The data equate to an impressive 63% reduction in gastric ulcers. We expected the ASA cohort to offer a gastric ulcer rate around 10% and PA-325/40 to be low-single digits. These results are consistent with our expectations and show the powerful efficacy of Pozen’s drug. When duodenal ulcers were included in the analysis, the reduction increased to 71%. Data on new or worsening erosive esophagitis showed an astonishing 87% reduction in favor of Pozen’s PA-325/40 versus EC-ASA 325 mg. Discontinuation rates and treatment success at six months also showed strong statistical significance in favor of Pozen’s PA-325/40 versus EC-ASA 325 mg. At six months, the observed incidence of discontinuations due to pre-specified upper-gastrointestinal events was significantly lower with PA-325/40 vs. EC-ASA 325 mg, 1.5% vs. 8.2%, p<0.001. Treatment success at six months was 95.2% for PA-325/40 vs. 83.2% for EC-ASA 325 mg, a 14% improvement in outcome based on intent to treat (p<0.001).
Secondary analysis also show statistically significant reductions in the presence of heartburn as reported on a standardized questionnaire at month 1, 3, and 6. A post-hoc esophageal mucosal assessment showed a meaningful and statistically significant reduction in new esophageal erythema (2.7% vs. 7.6%, p<0.001) and new esophageal erythema or new or worsening erosive esophagitis (4.8% vs. 22.5%, p<0.001). Treatment-emergent adverse events, included GERD, esophagitis, erosive esophagitis, or reflex esophagitis was 6.1% for PA-325/40 versus 23.9% for EC-ASA 325 mg (p<0.001).
The data above was presented in poster form (Poster 608: "PA32540 [Enteric-coated Aspirin 325 mg + Immediate-release Omeprazole 40 mg] Is Associated with Significantly Fewer Gastric Ulcers and Significantly Less Endoscopic Erosive Esophagitis than Enteric-coated Aspirin [EC-ASA] Alone: Results of Two Phase 3 Studies.") at the American College of Gastroenterology (ACG) meeting on October 22, 2012 in Las Vegas, NV. Pozen received two awards for its poster. The first award was the ACG Auxiliary Award for $1,000 to the primary authors of the two best papers presented at ACG2012. The $1,000 is hardly anything to get excited about, but over 1,600 posters were presented at ACG this year. The fact that Pozen's poster was considered one of the two best posters certainly says something about the quality of the data and the excitement it generated from the attendees.The second award was the prestigious Presidential Poster Award. According to the ACG's website: "The ACG Educational Affairs Committee will identify the most highly ranked abstracts selected for the poster sessions in each category and acknowledge their achievement with the ACG Presidential Poster Award. These recipients will receive a special commendation on their poster in the Poster Hall, a certificate of achievement, and recognition in the meeting program book." All posters are eligible for this award. Similar to the Auxiliary Award, the fact that Pozen's poster of the phase 3 data was selected to win the Presidential Poster Award certainly validates the quality of the data and the efficacy of the drug. We think this type of data and recognition by the ACG could help drive meaningful market share for PA-325/40 post approval.
Pozen's PA-325/40 is a combination pill containing enteric-coated aspirin 325 mg surrounded by a pH-sensitive film surrounded by an immediate-release omeprazole 40 mg.
Pozen designed the drug for patients requiring daily aspirin for secondary cardiovascular prophylaxis who are at risk for aspirin-associated gastric ulceration. Low-dose aspirin (ASA) is recommended for the secondary prevention of cardiovascular (source
) and cerebrovascular (source
) events. However, daily aspirin therapy is associated with adverse gastrointestinal events, including gastric ulceration and bleeding, as well as dyspepsia and GERD-like symptoms (source
) which may limit the patient compliance and continued use (source
). Proton-pump inhibitors, like omeprazole, are recommended to reduce the risk of upper gastrointestinal injury in patients at risk for potentially harmful events associated with chronic daily aspirin use (source
), including dyspepsia and GERD (source
The Phase 3 trial above was designed to evaluate whether PA-325/40 is associated with fewer gastric ulcers and fewer upper gastrointestinal (UGI) symptoms compared with EC-ASA 325 mg alone. A full presentation of the data can be found HERE
We expect Pozen to be in position to file the new drug application (NDA) for PA-325/40 during the first half of 2013. We still believe that Pozen will be able to secure a U.S. commercialization partner for the drug in the near future. An upfront payment for PA could be in the area of $15 to $20 million, along with over $150 million in back-end milestones and royalties on sales. A deal that includes countries outside the U.S. presents upside (perhaps a doubling) to these figures. As a point of reference, the Vimovo transaction with AstraZeneca
(NYSE:AZN) provided $40 million upfront, $45 million in approval milestones, and $290 million in sales milestones plus roughly 10% royalties on sales. Pulling in a deal of this magnitude has the potential to double the stock.