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Positive Results from Trial of Nasally Administered Apomorphine for Erectile Dysfunction

HAUPPAUGE, NY -- December 13, 2001 -- Nastech Pharmaceutical Company Inc. reported the results of a Phase II clinical trial in 184 men with erectile dysfunction (ED) that concluded its nasally administered apomorphine formulation demonstrated excellent efficacy, was well tolerated with minimal side effects, and has an onset of action, about 15 minutes after dosing, that uniquely matches normal human sexual response physiology. The study supports the final stages of the clinical development of the product and Nastech expects the pivotal Phase III trials to begin early next year.

"These results support our belief that nasally administered apomorphine may be an attractive alternative to the PDE-5 inhibitor class of therapies in the treatment of erectile dysfunction, and thus represents a significant commercial opportunity to address the multi-billion dollar worldwide ED market," said Steven C. Quay, M.D., Ph.D., Chairman, President and Chief Executive Officer of Nastech. "We are currently in negotiations to complete a worldwide development and marketing agreement for this product and we believe the results of this study strongly support these commercialization efforts."

Normal human sexual response begins with sensory input to the brain. The focus of this "central" input is the hypothalamus, a region of the brain that, among other functions, controls erectile function via nerves from the brain via the spinal cord to blood vessels in the penile tissue. Apomorphine is a potent dopamine agonist that promotes erectile function by stimulating receptors in the hypothalamus. The PDE-5 inhibitor class of ED therapies does not function in the brain but only on the final step in erectile function. In addition, unlike the class of PDE-5 inhibitors that produce hypotension, headaches, and other side effects due to non-specific interactions in the body, apomorphine acts specifically on the D1/D2 class of dopamine receptors that are responsible for the initiation of the erectile response in the brain. Nastech's nasally administered formulation is the subject of numerous patent applications in the U.S., European Union countries, Japan, and other major countries.

Prior pharmacokinetic trials indicated that nasally administered apomorphine has a maximum blood level about 15 minutes after dosing and also appears in the cerebral spinal fluid at high levels within 20 minutes after administration. Therefore, this trial was designed to obtain efficacy data 15 minutes after dosing. Research begun in the 1950s by Masters and Johnson and others demonstrate that this time of onset coincides with normal human sexual response physiology.

The study involved men up to 75 years of age with ED of all etiologies (50 percent psychogenic, 26 percent mixed organic, and 24 percent diabetic) and severities (64 percent were moderate or severe at baseline as judged by the IIEF domain score). There were no patient restrictions as to prior use of ED medications nor was pre-qualification with use of a RigiScan® (indicative of mild erectile dysfunction) needed for inclusion in the study. The men were randomly placed in four dosage groups: placebo, 0.25 mg, 0.50 mg, and 1.0 mg apomorphine with treatment consisting of up to 18 doses and efficacy recorded after every administration and after every eight doses using validated ED efficacy questionnaires. The treatment group demographics were not different with respect to age (mean of 56 to 60 years), ethnicity, ED etiology, or ED severity.

The ability to achieve some erection was found in 81 percent, 89 percent, and 91 percent of the men treated with 0.25 mg, 0.50 mg, and 1.0 mg nasally administered apomorphine, respectively. With respect to erections sufficient for vaginal penetration, 69 percent, 73 percent, and 82 percent of men reported success in the three-apomorphine dosage groups compared to 35 percent for the placebo group (1.0 mg vs. placebo, p < 0.0001). Nasally administered apomorphine compared to placebo also demonstrated statistically significant improvements in erectile function (including erection sufficient to complete sexual intercourse with ejaculation), confidence in erection, orgasmic function, and intercourse satisfaction.

No significant adverse events were reported among the 184 patients enrolled in the study. Side effects were infrequent, mild to moderate in intensity, of short duration, and resolved without intervention. Side effects above 1 percent were unusual taste (5 percent) and dizziness (3 percent). There were no reported instances of hypotension, syncope or pre-syncopal events, including vomiting, sweating, flushing or vasodilatation, hot flashes, or pallor.

SOURCE Nastech Pharmaceutical Company Inc.

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