August 11, 2008
Altus Pharmaceuticals Announces Achievement of Primary Endpoint in Phase 3 Efficacy Trial of Trizytek for Cystic Fibrosis Patients With Pancreatic Insufficiency
Altus Pharmaceuticals Inc. (NASDAQ: ALTU) announced today that its Phase 3 efficacy trial of Trizytek(TM) (porcine-free enzymes) in patients with cystic fibrosis (CF) successfully met its primary endpoint of improvement in fat absorption. The Company released top-line results from its 163 patient, double-blind, placebo-controlled trial of Trizytek, an enzyme replacement therapy for patients with pancreatic insufficiency. Trizytek is a stable and pure combination of three active enzymes in a fixed-ratio that is designed to improve fat, protein and carbohydrate absorption in pancreatic insufficient individuals. Altus' Trizytek Phase 3 clinical program is the largest ever conducted to evaluate the efficacy and safety of pancreatic enzyme replacement therapy in cystic fibrosis patients. Detailed trial results will be presented at the North American Cystic Fibrosis Conference in October 2008.
The trial met its primary efficacy endpoint with statistical significance. In cystic fibrosis patients with exocrine pancreatic insufficiency, Trizytek demonstrated a statistically significant improvement of fat absorption over placebo through the measurement of the coefficient of fat absorption (CFA). The primary efficacy analysis was an intent to treat (ITT) analysis in the sub-group of patients with severe malabsorption (baseline CFA below 40). In addition, data were analyzed for the overall group, which included all patients with baseline CFA below 80.
Patients treated with Trizytek had a statistically significant improvement in CFA compared to placebo. In the Trizytek CFA below 40 group, there was an improvement in the mean CFA of 20.2 (80% change from baseline). In the placebo CFA below 40 group, there was an increase in mean CFA of 5.1 (24% change from baseline). The mean difference between groups for the change in CFA was 15.1 (p=0.001).
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In the overall group that received Trizytek, there was an improvement in the mean CFA of 11.3 (36% change from baseline). Patients on placebo, in the overall group, remained relatively unchanged with a mean CFA of 0.2 (4% change from baseline). The mean difference between groups for the change in CFA was 10.6 (p=
Primary Endpoint - CFA Results
Trizytek Placebo Mean p-value difference between groups Baseline Baseline Improvement Baseline Improvement CFA from from Group baseline baseline --------- -------- ----------- -------- ----------- below 40 20.2 points 5.1 points or or 79.6 24.4 30.0 percent 28.1 percent 15.1 0.001 Overall 11.3 points 0.2 points below or or 0.001 35.8 4.3 percent 46.9 percent 49.5 10.6
"We are pleased to have met our primary endpoint for improvement in CFA with Trizytek and this achievement is a major milestone for our company. The outcomes were driven by the strong positive data from the 26 centers in the U.S., where we will be initially seeking approval upon completion of our long-term safety studies," stated Dr. Georges Gemayel, President and Chief Executive Officer of Altus Pharmaceuticals. "Our overall top-line results were affected by a marked difference between patients within the U.S. and outside of the U.S. Although we have not yet analyzed individual patient data, on aggregate, patients from 3 out of 6 non-U.S. countries did not appear to show a difference between Trizytek and placebo groups."
Dr. Gemayel continued, "We are currently investigating possible factors that may have affected the results outside the U.S. and upon completion of the investigation, we will report the findings. Moving forward, we have requested a pre-NDA meeting with FDA to discuss these results and we remain committed to driving Trizytek toward commercialization."
Of the 138 patients in the ITT analysis, 68 patients were at CF centers within the United States and 70 patients were at sites outside of the United States. A strong country effect was seen that impacted the overall outcome. For U.S. patients in the Trizytek CFA below 40 group, there was an improvement in the mean CFA of 28.4 (115% change from baseline). In the placebo CFA below 40 group, there was an increase in mean CFA of 3.4 (23% change from baseline). The mean difference between groups for the change in CFA was 25.1 (p =0.001). In contrast, the mean difference in the CFA below 40 group in countries outside of the U.S. was 5.0.
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For U.S. patients in the overall group who received Trizytek, there was an improvement in the mean CFA of 15.7 (48% change from baseline). For U.S. patients on placebo in the overall group, there was a decrease in the mean CFA of -2.1 (1% change from baseline). The mean difference between groups for the change in CFA was 17.5 (p=
Primary Endpoint - CFA Results - US Sites
Trizytek Placebo Mean p-value difference between groups Baseline Baseline Improvement Baseline Improvement CFA from from Group baseline baseline -------- -------- ----------- -------- ----------- below 28.4 points 3.4 points 40 or or 115.4 22.6 27.0 percent 23.6 percent 25.1 0.001 Overall 15.7 points -2.1 points below or or 0.001 48.3 0.7 percent 46.3 percent 43.7 17.5
The trial also evaluated secondary efficacy endpoints. Patients treated with Trizytek had a statistically significant improvement in coefficient of nitrogen absorption (CNA, which measures protein absorption) compared to placebo (p =
Trizytek was well-tolerated and had a favorable safety profile in the trial. There were no serious adverse events attributed to the Trizytek treatment.
Drucy Borowitz, M.D., Professor of Clinical Pediatrics, State University of New York, Director, Cystic Fibrosis Center, Women and Children's Hospital of Buffalo, and principal investigator of the DIGEST trials commented, "The data are very compelling and the results from the CF centers in the U.S. confirm the Phase 2 study, which was conducted solely in the U.S. During my 20 years of treating CF patients, I have seen significant advancements in patient care and Trizytek is a good example of an innovative drug that has the potential to enhance nutritional outcomes, which are strongly correlated with pulmonary status."
Dr. Borowitz added, "Trizytek has the potential of being formulated for young children and other patients who cannot swallow capsules."
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"We are very encouraged by the Trizytek efficacy data because this treatment will offer important new benefits to CF patients who need enzyme replacement therapy," said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. "Currently, the dosing regimens for enzymes can be a challenge for patients. The one capsule per-meal dosing for Trizytek will help drive better compliance and therefore enhance long-term patient health outcomes. Since 2000, the Foundation and Altus have worked together toward a goal of bringing this new treatment to the market. The data reported today reinforces our business model of supporting highly innovative therapies for CF patients."
Dr. Gemayel concluded, "The Trizytek clinical program demonstrates our commitment to advancing novel enzyme replacement therapy options for both cystic fibrosis patients and others who suffer from pancreatic insufficiency. Due to the uncertainties with therapeutics that contain animal-derived ingredients, we believe there is a need for new products that are derived from recombinant technology such as Trizytek. I would like to thank all of the investigators, study coordinators, dieticians, patients and patient families who participated in this trial. In addition, I would like to acknowledge the Cystic Fibrosis Foundation for its continuing support. Reaching this milestone was a great group effort by all parties involved."
The Company will host a conference call to discuss the results at 4:30 p.m. ET on August 11. The call may be joined via telephone by dialing (877) 440-5803 or (719) 325-4879 (for international participants) at least 5 minutes prior to the start of the call. The conference confirmation code is: 8326549. For 72 hours following the call, an audio replay can be accessed by dialing (719) 457-0820 or (888) 203-1112 and using the conference confirmation code 8326549.
A live audio webcast of the call will also be available on the "Investor Relations" section of the Company's website, www.altus.com. An archived audio webcast will be available on the Altus website approximately two hours after the event and will be archived for 30 days.
Cystic fibrosis is a life-threatening genetic disease that affects approximately 30,000 children and adults in the United States. It causes serious lung infections and digestive complications, including poor absorption and digestion of food. Most people with CF need to take pancreatic enzyme supplements with meals and maintain a high-calorie diet to help their bodies absorb the proper level of nutrients.
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The DIGEST Trials
The DIGEST trials (Determining the efficacy and safety of an Innovative GastrointESTinal enzyme complex) are Altus' Phase 3 Trizytek clinical program, which consists of an efficacy trial and two safety trials. Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the drug discovery and development affiliate of the Cystic Fibrosis Foundation, have supported the CF studies. The DIGEST efficacy trial, which tested a one capsule per-meal dosing regimen, was designed to study fat absorption in cystic fibrosis patients with exocrine pancreatic insufficiency through the measurement of the coefficient of fat absorption (CFA). In addition to the efficacy trial, the DIGEST trials include two studies to evaluate the long-term safety of Trizytek over one year of open-label treatment in cystic fibrosis and chronic pancreatitis patients with exocrine pancreatic insufficiency.
About Trizytek (porcine-free enzymes)
Trizytek has the potential to be the first porcine-free enzyme replacement therapy for patients with pancreatic insufficiency. Pancreatic insufficiency is a condition that affects most cystic fibrosis patients, as well as many patients with chronic pancreatitis. In these diseases, a deficiency of pancreatic enzymes causes poor absorption of essential nutrients, which often leads to malnutrition, impaired growth and reduced survival. Trizytek is intended to replace missing digestive enzymes with one capsule per-meal to promote and maintain proper digestion and growth in affected patients. Altus is developing Trizytek to enhance health outcomes by offering significant patient advantages such as improved and more consistent dosing that we expect will drive better long-term compliance. Utilizing recombinant technology, Trizytek is manufactured by blending three drug substance enzymes: lipase, protease and amylase. This consistent and pure enzyme combination is designed to improve fat, protein and carbohydrate absorption in pancreatic insufficient individuals.
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About The Current Pancreatic Enzyme Replacement Market
The enzyme products in use today for pancreatic insufficiency as well as those in development are all porcine-derived and require patients to take multiple capsules with every meal or snack. These pancreatic enzyme replacement products have been marketed since before the enactment of the Food, Drug and Cosmetic Act in 1938 and are not marketed under new drug applications, or NDAs, approved by the United States Food and Drug Administration, or FDA. In April 2004, the FDA issued a notice that manufacturers of existing pancreatic enzyme replacement products will be subject to regulatory action if they do not obtain approved NDAs for those products by April 28, 2008. In October 2007, the FDA issued an update to the 2004 notice and announced that it has extended the deadline for unapproved pancreatic enzyme drug products from April 28, 2008 to April 28, 2010, but only if the manufacturers have investigational new drug applications on active status on or before April 28, 2008 and have submitted NDAs on or before April 28, 2009. According to IMS Health, global prescription sales of existing pancreatic enzyme replacement products were approximately $858 million in 2007.
About the Cystic Fibrosis Foundation
The mission of the Cystic Fibrosis Foundation is to assure the development of the means to cure and control CF, and to improve the quality of life for those with the disease. CFFT is the nonprofit drug development affiliate of the CF Foundation that operates drug discovery, development and evaluation efforts. Total support for CFFT is provided by the CF Foundation. The CF Foundation has initiated a special gifts campaign, Milestones to a Cure, with a target goal of $175 million to support programs like the one with Altus. For more information, call (800) FIGHT CF or visit www.cff.org.
About Altus Pharmaceuticals Inc.
Altus Pharmaceuticals, headquartered in Cambridge, MA, is a biopharmaceutical company focused on the development and commercialization of oral and injectable protein therapeutics for patients with gastrointestinal and metabolic disorders. The company is listed on the Nasdaq Global Market under the symbol ALTU.
Safe Harbor Statement
The statements in this press release regarding the preliminary, top-line assessment of the Phase 3 data and its implications for remaining Phase 3 trials, the future development of Trizytek, and the timing of any filing of an NDA with the FDA for Trizytek are forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In particular, these statements are subject to the risk that further analyses of the Phase 3 data may lead to different (including less favorable) interpretations of the data than the preliminary analyses conducted to date and/or may identify important implications of the Phase 3 data that are not reflected in these statements. Clinical trial data are subject to differing interpretations, and regulatory agencies, medical and scientific experts and others may not share the Company's views of the Phase 3 data, or its implications for the remaining Phase 3 trials, the future development of Trizytek, and the timing of any filing of an NDA with the FDA for Trizytek. In addition, further analyses of the Phase 3 data and discussion with regulatory authorities may lead to important modifications to the development plan for Trizytek, including delays in commercialization. The FDA may not view the improvement in CFA as substantial enough to warrant approval and may be unwilling to consider the US-only data in its analysis. There can be no assurance that Trizytek will ever receive regulatory approval or be successfully commercialized. Other risks and uncertainties that could cause actual results to differ materially from those expressed or implied by these forward-looking statements include those detailed from time to time in the Company's periodic reports filed with the Securities and Exchange Commission, including the Company's current reports on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K, particularly the discussion under the caption "Item 1A, Risk Factors" in the Company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2008, which was filed with the Securities and Exchange Commission on August 5, 2008. The forward-looking statements in this press release are qualified by these risk factors. We assume no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.
Altus and the Altus logo are the registered trademarks of Altus Pharmaceuticals. Trizytek and DIGEST Trials are trademarks of Altus Pharmaceuticals.