Regeneron Pharmaceuticals Inc. is a step closer to cashing in on its serendipitous discovery that Axokine modified ciliary neurotrophic factor induces weight loss, as Phase II results announced last week showed the protein's ability to cause weight loss in severely obese patients. The next hurdle for Axokine will be to show that results can be sustained at one year with minimal side effects.

CNTF is a distant relative of leptin. It activates leptin-like pathways in the hypothalamus but works in forms of obesity resistant to leptin treatment. REGN created a truncated and modified version of the protein to reduce its immunogenicity and increase its potency.

Axokine originally was tested as a treatment for amyotrophic lateral sclerosis, where it failed to show efficacy at doses of 15 mg/kg to 30 mg/kg (see BioCentury, Jan. 13, 1997). But weight loss also was seen as a side effect. A dose ranging Phase I trial for obesity showed unacceptable adverse effects including nausea, vomiting and herpes cold sores at high doses.