Altus Pharmaceuticals Inc announced that its phase-3 efficacy trial of Trizytek (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 programme 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<40 group, there was an improvement in the mean CFA of 20.2 (80 per cent change from baseline). In the placebo CFA<40 group, there was an increase in mean CFA of 5.1 (24 per cent change from baseline). The mean difference between groups for the change in CFA was 15.1 (p=0.001).

"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 US, 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 US and outside of the US. Although we have not yet analyzed individual patient data, on aggregate, patients from 3 out of 6 non-US 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 US 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."

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."

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.

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 non-profit drug development affiliate of the CF Foundation that operates drug discovery, development and evaluation efforts.

Altus Pharmaceuticals, headquartered in Cambridge, is a biopharmaceutical company focused on the development and commercialization of oral and injectable protein therapeutics for patients with gastrointestinal and metabolic disorders.