Nastech reports positive obesity and sexual dysfunction data

Washington State-based Nastech Pharmaceutical has reported positive results from a Phase Ib study with PYY 3-36 (PYY) nasal spray for obesity and positive results from a Phase II Maximum Tolerated Dose (MTD) study with apomorphine nasal spray for sexual dysfunction.

In January 2004, Nastech initiated a Phase I-B dose-range finding study in healthy overweight men and women with a Body Mass Index of 27-40 kg/m². The study was a randomised five-way crossover, double-blind, placebo-controlled trial with assessment of appetite and food intake for the 24-hour period (from lunch one day to breakfast the next day) following a single administration of a PYY nasal spray or a placebo nasal spray before the lunch meal. Pharmacokinetics, vital signs, nasal tolerance and safety were also evaluated.

Eleven subjects completed the study; one dropped out due to problems of venous access for the blood draws. Results in 9 of 11 subjects indicate that a single dose of PYY nasal spray reduced average calorie intake for each meal, with the greatest reduction at the lunch meal, and overall for the 24-hour period. PYY also reduced appetite, as determined by Visual Analog Scale assessment, and was well tolerated; side effects were generally mild and all resolved without treatment. Two subjects did not respond. Nastech is developing intellectual property around the understanding of this difference.

'We are encouraged by the results of this Phase Ib PYY study since we are seeing appetite reduction, calorie reduction, even without dietary intervention or behavioral changes, and a well tolerated safety profile,' commented Dr Gordon Brandt, executive vice president, Clinical and Medical Affairs. 'Once the Phase Ib and Phase Ic studies are completed and the data is analysed we hope to be in a position to advance the program into Phase II weight loss studies.

Apomorphine MTD

The MTD study, initiated in June 2003, was designed to determine if typical apomorphine-related side effects, such as hypotension or low blood pressure, nausea, vomiting or syncope, the medical term for fainting, occur with the nasal dosage form and if they do, at what dose they occur. The multi-center, double blind, placebo-controlled study enrolled 102 men age 50 to 82 years approximately half of whom had erectile dysfunction. The study involved a single daily active- or placebo-dose administration for seven consecutive days. Doses began at 0.5 mg and escalated in increments of

0.25 mg. Vital signs were measured both supine and standing to observe orthostatic effects and ECG measurements were taken during the five hours after each dose.

  Based on the results of this study, doses up to 1.75 mg are safe and well tolerated and doses up to 2.0 mg are acceptable for further in-clinic safety studies. Results indicate that there is no clinically or statistically significant effect on the group means for systolic, diastolic, or mean arterial blood pressure, supine or standing, at doses up to 2.0 mg nor is there a trend across dosage groups.

'The substantial safety profile difference between our nasal dosage form of apomorphine and the sublingual dosage form in apomorphine in clinical trials to date, as well as its efficacy, is a demonstration of the value proposition for nasal delivery of apomorphine,' stated Dr Steven Quay, chairman, president and chief executive officer of Nastech. 'The next step for this program is to submit this data together with protocols for further studies to the FDA and to obtain regulatory guidance on a program intended to permit development, and if successful, approval and marketing of apomorphine nasal spray for sexual dysfunction.'