West Coast Editor

Despite a somewhat ambivalent vote by its advisory panel, the FDA approved a label expansion for Cubist Pharmaceuticals Inc.'s antibiotic Cubicin (daptomycin), which now can be used against infections in the bloodstream and heart valves, as well as skin.

The company's stock (NASDAQ:CBST) closed Friday at $25.55, up $4.30, or 20.2 percent.

Launched in late 2003 to target the skin indication, injected Cubicin now is cleared for a much broader indication - Staphylococcus aureus bloodstream infections (also known as bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus, and methicillin-resistant S. aureus.

Cubist estimated that the infections account for 30,000 deaths in the U.S. each year. Given once per day at 6 mg/kg, Cubicin is the only intravenous antibiotic approved for the disorders.

The company based its supplemental new drug application on positive data from a Phase III trial, disclosed last summer. (See BioWorld Today, June 29, 2005.)

Rodman & Renshaw in New York initiated coverage on Friday of Cubist, rating the stock "market outperform" and setting a price target of $34, but Lazard Capital Markets, also in New York, was more circumspect.

Lazard's Joel Sendek, who has a "hold" rating on Cubist, maintained in a research report last month his 2006 Cubicin sales estimate of $191 million - the low end of the company's guidance, reiterated Friday: $190 million to $205 million.

"Our outer-year estimates are below management's peak sales projection of $500 million," Sendek added, predicting that "Cubicin will be used primarily as a second-line therapy or in high-risk patients."

Getting the drug beyond that segment "may be more challenging given its premium price and other unresolved issues" discussed during the FDA advisory panel meeting earlier this year.

Some of those issues had to do with labeling, and with left-sided endocarditis. The success rate in the presentation offered by Cubist at the panel meeting showed Cubicin was effective in 11 percent of left-sided patients.

"I don't think anyone would say that is effective therapy," said panel member and pediatrician John Bradley during the meeting. "However, there is not much that we have that is better. If you lump it in with all the other cases of infective endocarditis, [Cubicin] was not inferior," he added.

Patients with uncomplicated bacteremia "can't be extrapolated to [have] left-sided endocarditis," Bradley added, "but I think people with right-sided endocarditis are pretty much the same as complicated bacteremias."

As a reason to recommend approval, he cited Cubist's claim that 25 percent of off-label use of daptomycin was against bacteremia.

Eileen McIntyre, director of corporate communications for Lexington, Mass.-based Cubist, confirmed Friday that 50 percent of the drug's use was off-label, half of it for bacteremia, "but having said that, we had a very tiny share of that market."

The panel ended up voting unanimously to recommend Cubicin for bacteremia, but split 5-4 in favor of the endocarditis indication.

Some panel members were "a little uncomfortable" with the endocarditis indication, especially left-sided, McIntyre acknowledged.

"In the label, it does indicate there were too few patients to conclusively show efficacy in left-sided cases," she told BioWorld Today.

The expanded label is posted on the company's website.

Ilya Kravets, analyst with Rodman & Renshaw, noted in a research report that the new indications "closely reflect" the FDA panel talks, and estimated that the expanded label could mean as much as $235 million in Cubicin sales in the U.S. by 2009.

The drug, which Kravets believes has "potential to be the next standard therapy for bacteremia," is partnered in Europe with Basel, Switzerland-based Novartis AG.

Cubicin is being evaluated in several trials for the treatment of other complicated infections, and the firm is expected to meet with the FDA in the second half of this year to discuss Phase III plans for a new indication, probably osteomyelitis, he wrote.

Meanwhile, deaths from endocarditis, even with antibiotic treatment, are 25 percent to 40 percent - and 100 percent without therapy, McIntyre said.

"Left-sided tends to be more severe because that's the side that's doing most of the pumping, but I haven't seen fatalities broken out for left and right," she said. "There's an incredible unmet need out there that led us to do a very difficult, long trial."

The cost of Cubicin therapy varies.

"Patients can be treated between two and six weeks, and of course, it depends on the weight of the patient," McIntyre said.

Before April, when Cubist raised the price 6.5 percent, the approximate cost for treating skin infections (dosed at 4 mg/kg) was $100 per day, and $150 per day for other indications, she said.

No Comments