By Randall Osborne
West Coast Editor
A double-whammy of bad news for Nabi - early data from a Phase III trial of its product against blood infections, which failed to meet the study's primary endpoint, and problems with a supplier, which are expected to put a dent of $4 million to $5 million in third-quarter earnings - sent the company's stock (NASDAQ:NABI) tumbling more than 40 percent, closing Tuesday at $5.56, down $3.81.
Preliminary data from the double-blinded, placebo-controlled Phase III trial of Nabi's Staphylococcus aureus conjugate vaccine, StaphVAX, in 1,804 end-stage renal disease patients on hemodialysis showed a 57 percent reduction of bloodstream infection for the first 10 months.
But the primary endpoint was one year, and StaphVAX failed to achieve statistical significance at that duration.
"It's a very positive outcome for this trial," said Gary Horwith, vice president of clinical research and medical affairs for Nabi. "What we need to address at this point is ways to boost the vaccine, and make it more durable [in the patient population studied]. We planned to do that anyway in Phase IV."
Jonathan Gal, analyst and president of Biocoverage Inc. in Cambridge, Mass., said positive data even at 10 months for this indication constitute "a milestone in medical history. I think there's still a good chance the FDA will give them a green light and let them file for a [biologics license application] because of the environment around the disease. It's serious."
Gal called the stock "an excellent buying opportunity" for longer-haul investors.
Robert Wasserman, analyst with Sterling Financial Investment Group, of Boca Raton, Fla., where Nabi is located, said the company "has tried to paint a very positive picture of the data, but clearly it didn't meet the endpoint they were looking for. All the fast money's out of the stock, that's for certain."
StaphVAX is made of capsular polysaccharides from the two most common serotypes of S. aureus, each conjugated to a carrier protein. Data were disclosed at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy in Toronto.
Horwith told BioWorld Today testing the vaccine in patients with fully competent immune systems would have been preferable, but finding such patients suitable for a full clinical trial was nearly impossible.
"We knew we had an uphill battle going into it, using this patient population," he said, noting that many of those for whom StaphVAX might be used, if approved, would be patients undergoing surgery, who find themselves at high risk for a much shorter period.
Evaluating StaphVAX's efficacy for a shorter period, and building in the likelihood of boosters, was an option, Horwith added, but the 12-month endpoint is "kind of an arbitrary, but convenient and conventional time frame. There's nothing magic about it, and you know there's going to be a drop in antibodies over a period of time. It was the luck of the draw we saw [efficacy] at 10 months and not at 12 months."
The company will consult with the FDA about its next step.
Another question, Wasserman said, is whether Nabi can find a marketing partner to keep the work going.
"I'd say they have a pretty good chance," he said. "It's kind of a hot area, and they've certainly gotten plenty of money from the [National Institutes of Health]."
Meanwhile, Nabi said changes in production materials by Cangene Corp., of Winnipeg, Manitoba, and resulting demands by the FDA for a regulatory submission, have slowed the supply of the WinRho SDF human immune globulin product, which is marketed by Nabi with Cangene in the U.S. under a profit-sharing agreement. The drug is used to treat idiopathic thrombocytopenia purpura. Cangene, which owns and manufactures WinRho SDF, also manufactures Nabi-HB, a treatment for hepatitis B, under contract.
FDA requirements having been satisfied, shipment of Nabi-HB was resumed earlier this month, and the supply of WinRho SDF is expected to start again in a few weeks, Nabi said. Profits are expected to drop by $4 million to $5 million because of the delays.
Horwith said Tuesday's news of the trial data and the product delays together caused an exponential market impact. "They had a domino effect," he said.
In other news from ICAAC:
¿ AnorMED Inc., of Vancouver, British Columbia, presented data on AMD-8664, an orally administered drug candidate with the potential to block HIV from entering and infecting healthy T cells. AMD-8664 has exhibited inhibition of HIV infection and good oral absorption properties in preclinical studies.
¿ Aronex Pharmaceuticals Inc., of The Woodlands, Texas, presented clinical, preclinical and pharmacokinetic data for Nyotran, its product for systemic fungal infections. Results were positive in a Phase II clinical trial in refractory or intolerant patients with invasive Aspergillus, in a comparative urinary pharmacokinetics and drug disposition study, in efficacy trials in the treatment of disseminated candidiasis in guinea pigs and in a differential in-vitro antifungal activity study. Aronex anticipates submission of an NDA in 2001.
¿ Cubist Pharmaceuticals Inc., of Cambridge, Mass., reported positive safety and efficacy data on Cidecin (daptomycin for injection) in a completed Phase I dose-escalation study. Also, data from Cubist's two ongoing Phase II studies showed daptomycin had an overall clinical success rate of 93 percent in the intent-to-treat population and 100 percent on the clinically evaluable patients. Cidecin is an antibiotic that has demonstrated rapid bactericidal activity against Gram-positive bacteria, including strains resistant to current therapies.
¿ Gilead Sciences Inc., of Foster City, Calif., said it received positive results from a study in India examining the use of a single dose of AmBisome for injection as a treatment for visceral leishmaniasis (VL). The study explored AmBisome's efficacy and safety through a single dose in 203 immunocompetent patients with confirmed VL. At 30 days post-treatment, 196 patients were parasite free and at six months 183 were parasite free. VL is caused by the parasite Leishmania and is spread through the bite of a female sandfly.
¿ Laboratory Corp. Of America, of Burlington, N.C., gave its latest findings on HIV viral load trends in the U.S., stating that patients who were more frequently monitored had greater suppression of viral load. LabCorp used its proprietary database to examine more than 600,000 test results based on patient age, sex, race, geography and frequency of monitoring using its proprietary database.
¿ Tibotec, of Mechelen, Belgium, presented results on R165335-TMC125, one of its lead anti-HIV non-nucleoside reverse transcriptase inhibitors (NNRTI). NNRTIs are standard components of HIV combination therapy but cross-resistance HIV strains have limited the effectiveness of current NNRTIs. R165335-TMC125 inhibited 98 percent of all clinical isolates tested and 97 percent of the NNRTI resistant strains.
¿ Visible Genetics Inc., of Toronto, reported that the six-month Havana study in Europe showed that patients who received genotyping had a 50 percent greater reduction in their viral load than those patients who received standard-of-care treatment. Also, 15 percent more patients than in standard-of-care studies achieved viral loads of less than 400 copies/ml in the genotyping arms of the study. Both results were statistically significant and all viral resistance tests were performed using Visible Genetics' Trugene HIV-1 Genotyping Kit.