CD&D Washington Writer

Heart drugs aren’t all that controversial, but the approval of the heart failure drug BiDil raised some interesting questions. And its future is currently in doubt.

Conserving cash, NitroMed (Lexington, Massachusetts) in January halted sales and marketing activities for BiDil (isosorbide dinitrate and hydralazine hydrochloride), the first drug approved in the U.S. for a specific racial population, African-Americans. NitroMed receiving mountains of publicity in winning the approval — and critics generally questioning the gender-specific strategy.

CEO Kenneth Bate assured patients and health -care providers that while marketing activities will cease for the drug, BiDil will remain on the market. "We plan to keep BiDil available through all ordinary channels like many other drugs that are not actively promoted," Bate said during a conference call. "We will seek to assure that patients who are presently on BiDil continue to have access to the drug and will seek to continue to have the first status on health plans and hospital formularies."

While the firm "worked intensely" in 2007 on redirecting its sales and marketing efforts for BiDil, which resulted in an increase of new prescriptions by about 9% from the 3Q to 4Q, "the capital and the markets are not currently available to us on favorable terms" to sustain BiDil’s sales force and marketing activities, Bate said. The company also said it is eliminating 70 of its 90 jobs.

NitroMed had doubled its sales force last year to pump up profits for the drug, which had been sharply slower than predicted.

"We hired experienced, successful sales representatives," Bate said. He called early sales and prescription performance in 4Q07 "very encouraging and the result of the fourth quarter performance is that we are quite comfortable today in stating that BiDil is promotionally sensitive." But, he said, the firm was "forced to face economic reality."

"Ultimately, despite the best efforts of the entire organization, the results of our efforts have not been sufficient as to be sustainable," Bate lamented.

The firm has retained the investment banking firm Cowen and Co. "Nothing is off the table at this time and all strategic options are possible," Bate said

Analyst Robert Uhl, of Friedman, Billings, Ramsey and Co. (Arlington, Virginia), predicted that NitroMed’s hiring of Cowen could lead to the sale of the drug manufacturer, putting takeover valuation for the company of $1.78-$2.77 a share, or $82 million-$127 million.

Despite BiDil’s dreary sales, NitroMed is moving forward with its program to develop its once-daily, extended-release formulation of the drug, Bate told investors and analysts.

"To date, the program has gone well and we have not experienced any surprising obstacles," he said. "We are continuing our development of BiDil XR because it is our belief, and we have recent physician research to support this belief, that a once-daily formulation of BiDil will provide a level of convenience and compliance necessary to enhance the brand over the long term."

The FDA agreed at a Dec. 10 meeting that the firm’s proposed clinical development program was acceptable and, that if successful, the study results would be adequate for approval of the commercialization of BiDil XR, Bate maintained.

"We believe that we can finalize the formulation this year with the goal of initiating pivotal bioequivalence trials in 2009," he said. The company anticipates filing an approval application for BiDil XR in 2010, Bate added.

But analyst Liana Moussatos of Pacific Growth Equities (San Francisco) said "time-to-potential approval" for BiDil XR is "too long to benefit NitroMed."

Analyst Jennifer Chao of Deutsche Bank North American (New York) said the outlook for BiDil "remains very uncertain, at least in the near-to-medium term."

The pessimistic outlook for BiDil, NitroMed’s only marketed product and revenue source, puts shares of the firm "at significant risk," Chao added. However, she noted the upside risks for NitroMed include the "better-than-expected BiDil sales and positive clinical catalysts and news flow."

BioVascular gets ‘C’ $10.9M to boost vascular compounds

BioVascular (San Diego) has raised $10.87 million in Series C financing to support the clinical development of Saratin, a polypeptide derived from leech saliva, and BVI-007, a thrombopoietin antagonist that reduces platelet production.

The company has raised a total of $18.87 million. BB Biotech Ventures (Zurich, Switzerland) led the financing, with previous investors Merck (Germany) and Domain Associates (Princeton, New Jersey) joining the round. BB Biotech partner Martin Munchbach will join BioVascular’s board..

CEO John Parrish said Domain and Merck, two firms he previously had as investors in other companies he founded, both recommended BB Biotech as an investor.

"We had a number of meetings with them, and they did a lot of due diligence. This company has a bit of a European flavor," Parrish said, noting that Saratin was originally developed in Europe by Merck and is currently being tested in two Phase I/II clinical trials there for vascular graft failures due to intimal hyperplasia, the thickening of a blood vessel in response to an injury.

The first Phase I/II study, which involves patients undergoing hemodialysis vascular access graft surgery, has completed enrollment, Parrish said, adding that the company anticipates having three-month data in the near future and six-month data in late spring.

The second Phase I/II trial, which involves patients with peripheral arterial disease undergoing bypass graft surgery, has enrolled half of its planned 100 patient population, Parrish said.

BioVascular anticipates starting a Phase II study of Saratin in the U.S. later this year, he noted, adding that the firm expects to initiate pivotal Phase III trials of the compound in the U.S. and Europe in late 2009. BioVascular’s European Phase Ib dose-escalation study of BVI-007, a compound that acts to reduce platelet production without affecting platelet function, is expected to be completed in late spring, Parrish said.

Data from the Phase Ib study, which involves six cohorts of eight patients each, is expected in June, Parrish explained.

The $10.87 million is "enough money to last about a year," Parrish said, and "takes us to the point that we get some clinical data on Saratin and we get the [Phase] Ib efficacy data and understand the regulatory path on the BIV-007."

Nuvelo reports Phase 3 results for Alfimeprase

Nuvelo (San Carlos, California) reported results from the Phase 3 Novel Arterial Perfusion with Alfimeprase (NAPA) program evaluating alfimeprase in acute peripheral arterial occlusion (PAO).

Alfimeprase, the company’s lead product candidate, is a recombinant direct acting fibrinolytic (rDAF) shown to have the ability to dissolve blood clots by directly degrading fibrin.

In addition, Nuvelo says that alfimeprase’s thrombolytic activity appears to be localized to the site of delivery because it is rapidly inactivated by alpha-2 macroglobulin, a naturally occurring protein in the blood, as it moves away from the site of delivery and into the general blood circulation.

Alfimeprase is being studied in acute ischemic stroke and catheter occlusion (CO). The NAPA data were presented in a poster session by Fred Weaver, MD, professor of surgery and associate director of the University of Southern California Cardiovascular and Thoracic Institute, at the 2008 International Symposium on Endovascular Therapy in Hollywood, Florida.

In the NAPA-2 trial, the primary endpoint of 30-day open vascular surgery avoidance was achieved in 34.9% of patients receiving alfimeprase, 37.2% of patients receiving intra-thrombus (IT) placebo, and 18.4% of patients receiving peri-thrombus (PT) placebo. An interim analysis of the NAPA-3 study showed that 30-day open vascular surgery avoidance was achieved in 29.4% of patients receiving alfimeprase and 17.6% of patients receiving IT placebo.

Efficacy data from subjects with longer clots or smaller drops in alpha-2 macroglobulin, which rapidly and irreversibly inactivates alfimeprase, suggest improved retention of well as rates of hypotension and peripheral embolism, were numerically higher among patients receiving alfimeprase in both studies.

However, serious adverse events (SAE), major hemorrhage, cardiac events and infections were higher in subjects receiving alfimeprase in NAPA-2, but were higher in subject receiving IT placebo.

"We continue to believe that alfimeprase is an active thrombolytic agent when delivered in an optimized fashion, and we are focused on developing alfimeprase in stroke and catheter occlusion," said Michael Levy, MD, executive VP of R&D. "We continue to enroll patients in Phase 2 clinical trials in both these indications and expect top-line data from the SONOMA-3 catheter occlusion trial in the first half of 2008."

In brief ...

CV Therapeutics (Palo Alto, California), and Medlogics Devices (Santa Rosa, California) entered into an agreement under which Medlogics has licensed CV Therapeutics’ biopolymer stent coating technology to develop a drug-eluting stent.