West Coast Editor
The troubled development path of Alteon Inc.'s lead candidate alagebrium came to a temporary stop in two indications, after an interim look at Phase IIb data showed the drug failed to work against systolic hypertension, and the FDA put on clinical hold a Phase IIa trial with the same compound as a therapy for erectile dysfunction in diabetics.
A disheartened Wall Street sheared off more than half the company's stock value, causing Parsippany, N.J.-based Alteon's shares (AMEX:ALT) to close Friday at 31 cents, down 36 cents, or 53.7 percent.
Kenneth Moch, president and CEO of Alteon, said during a conference call that he would not try to "sugar-coat the disappointment we share in these two announcements," but remained certain of "a solid scientific foundation for alagebrium, including areas such as heart failure, endothelial dysfunction and renal disease."
The company has about $12 million in cash, he said, adding that "we run a very lean organization, under 50 people," and the firm is still figuring out what the burn rate will be in the near term.
Although alagebrium (formerly ALT-711), which targets the Advanced Glycation End-Product (AGE) pathway, has been observed to be safe and well tolerated in all trials so far, the independent efficacy review committee said an interim analysis found the SPECTRA study in uncontrolled systolic hypertension was yielding no effect and probably would miss its endpoints.
"I think it is important to note that we have spoken with a number of our advisers who were involved in the SPECTRA trial [and] the key comment was a continued belief in the activity of this compound," Moch said. "But the evidence, including SPECTRA, suggests that the effect is a central effect on the large arteries, and the peripheral effect is clearly more difficult to prove."
In the erectile dysfunction study for diabetics getting limited results with PDE5 inhibitors such as sildenafil citrate, the Division of Reproductive & Urologic Drug Products of the FDA's Center for Drug Evaluation and Research (CDER) decreed that the Phase IIa study be placed on clinical hold pending submission of more data. Early last month, Alteon said interim results from preclinical toxicity tests showed the liver alterations previously seen in rats, which had led to the voluntary suspension of trial enrollment, were not caused by genotoxicity pathways and might be a result of male rat metabolism - but CDER apparently was not convinced. (See BioWorld Today, Feb. 28, 2005.)
Judith Hedstrom, chief operating officer of Alteon, noted "there is a documented regulatory process by which they have to tell us in advance, in writing, what it is we would need to do to get off clinical hold, so [we are] not working in a vacuum. We expect to get that letter in a couple of days."
She said the company believes the "core answers are already available," although she allowed that "there are different levels of convincing, if you will, depending on who your audience is. We recognize that different people can look at the same data and need varying amounts of comfort to believe the conclusions."
The data likely will be submitted in the next few months, Moch said. Meanwhile, the company sticks to its knitting, Hedstrom said.
A Phase IIa heart failure trial is under way called PEDESTAL, which stands for "Patients with Impaired Ejection Fraction and Diastolic Dysfunction: Efficacy and Safety Trial of Alagebrium," which began in April 2004.
AGEs, protein-carbohydrate complexes that crosslink and lead to a loss of flexibility and function in body tissues and organs, "are everywhere," Hedstrom said. "In the past year and a half we have substantially kicked up our preclinical activities, specifically looking for areas where there is a rapid bridge from animal findings into Phase IIa proof-of-concept studies such as erectile dysfunction."
Next-generation molecules are being screened "as potential candidates in some other vascular diseases where the specific properties of the molecule need to be tailored to, say, a delivery system, for example," she said.