By Brady Huggett

Guilford Pharmaceuticals Inc. and partner Amgen Inc. completed a Phase II trial of NIL-A in patients with Parkinson¿s disease with less-than-pleasing results, not reaching statistical significance in any of its endpoints, but the analysis is not yet complete, Guilford said.

Guilford¿s stock (NASDAQ:GLFD) slid to a close of $16.15 Thursday, down $5.85, or more than 26 percent. Amgen (NASDAQ:AMGN) dropped $1.46, ending the day at $57.72.

¿This was an unprecedented study,¿ said Stacey Jurchison, director of corporate communications at Guilford. ¿This is a new class of compounds and it¿s a new biologic target and Parkinson¿s is a challenging indication to pursue. I think it¿s encouraging that we saw a positive trend and we are looking forward to completing the analysis of the data.

¿The purpose was to explore a high and low dose,¿ she added.

The randomized, double-blind, placebo-controlled trial involved 300 patients with mild to moderate Parkinson¿s disease ¿ split into three nearly equal arms¿ and took place at 42 medical centers. A third of the patients received placebo, a third a low dose and a third a high dose. The primary endpoint was at least a four-point improvement when compared with placebo in the UPDRS Motor Subscale measured before patients took their first daily dose of anti-Parkinson¿s medication. Secondary endpoints were SPECT brain scans, total UPDRS score, bilateral finger tapping, dyskinesia rating scale, Hoehn & Yahr rating scale and quality-of-life measures obtained from a questionnaire.

In mean UPDRS motor scores, in which increased scores indicate worsening disease, the change in placebo patients was -1.05, the low dose was .25 and the high dose -.35 (p=0.2). The SPECT measurements also failed to show statistical significance at 12 and 24 weeks (p=0.4 and 0.7, respectively). Hoehn & Yahr scores improved the most in high-dose patients and the least in placebo patients, and the difference between high-dose patients and placebo was statistically significant (p=0.028), but only after adjusting for age, duration of Parkinson¿s disease symptoms, and Hoehn & Yahr score at baseline. Changes in dyskinesia scores and finger-tapping tests were not statistically significant, either.

But there are bright spots, Jurchison said.

¿Some of the data suggest there may be a trend indicating a dose-response effect,¿ she said, adding that the drug had no safety issues all the way up to 1,000-mg doses taken orally four times a day.

Neuroimmunophilin ligands are small-molecule drugs designed to cross the blood-brain barrier and induce nerve growth.

Guilford, of Baltimore, and Amgen, of Thousand Oaks, Calif., began the Phase II study of neuroimmunophilin ligands for Parkinson¿s disease about a year ago. (See BioWorld Today, Aug. 8, 2000.)

The companies began their collaboration on neuroimmunophilins in 1997, through a deal that still has eye-popping potential nearly four years later ¿ $465.5 million to Guilford, best case scenario, with $392 million of that attached to development milestones. Amgen would have to get drug approval for all 10 indications mapped out in the deal in order for Guilford to pull in all the booty. At the time, the deal was considered to be one of the most lucrative deals in biotechnology. (See BioWorld Today, Aug. 22, 1997.)

Jurchison said Guilford and Amgen are working together to evaluate the data, and it is too premature to determine the next step either will take. The other nine indications in their deal are in preclinical work, Jurchison said.

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