Shares of Cardiome Pharma (CRME:Nasdaq) were among the worst-performing health-related stocks Wednesday, tumbling 21% after the drug developer said the Food and Drug Administration refused to accept its partner's application for an investigational drug to treat atrial fibrillation. The partner, Astellas Pharma, received a so-called "refusal to file" letter from the FDA. "We are very disappointed to communicate this setback to our stakeholders," Cardiome said in a press release. "Based on the clinical data generated from this program, we had great confidence that the submission would have met the Agency's filing requirements." In its letter to the company, the FDA said there were inconsistencies and omissions in the database that was submitted with the company's new drug application. Cardiome said it would not be deterred by the setback. "Our confidence in this program is in no way affected by this event," it said. "We are reviewing our own efforts in relation to this NDA, and are fully committed to resolving the FDA's concerns as quickly as possible." Shares of Cardiome recently were trading down $2.43 to $8.85. Shares of Connectics (CNCT:Nasdaq) fell 6% after the pharmaceutical company said it received notice from its debt holders warning of a potential default on its convertible notes. The company hasn't complied with the terms of its convertible debt obligation because of its failure to file its quarterly report for the period ending March 31 with the Securities and Exchange Commission in a timely manner. Connectics has 60 days to remedy the situation. "If the company does not cure this breach within this period, an event of default will occur under the indentures, and the trustees or the holders of at least 25% in aggregate outstanding principal amount of each note may accelerate the maturity of that note, causing the outstanding principal amount to be due and payable at that time," Connectics said. The company said that it is "endeavoring" to file the delinquent report within the next 60 days, which would allow it to avoid a default on the notes. Shares were trading down 75 cents to $11.85. Isis Pharmaceuticals (ISIS:Nasdaq) rose 3% after the company said it will sell up to $75 million in stock over the next 18 months as part of an equity financing deal with venture capital firm Azimuth Opportunity. "Isis Pharmaceuticals may at its discretion, from time to time, sell registered shares of its common stock at a small discount to the market price to Azimuth Opportunity," the company said. Isis plans to use proceeds from the financing for research, drug discovery, capital expenditures and general corporate purposes. Shares rose 21 cents to $7.67. Shares of Regeneron Pharmaceuticals (REGN:Nasdaq) rose 8% after the drugmaker said its chronic inflammation treatment received fast-track status from the FDA. "With no medical treatments approved to treat the chronic inflammation generated in people with these rare conditions, we hope the 1L-1 Trap will provide a new option for these patients in the future," the company said. Regeneron said it expects to provide top-line efficacy data from the trial of its treatment by the end of 2006. Shares were up 96 cents to $12.52. Cubist Pharmaceuticals (CBST:Nasdaq) fell 9% after the biopharmaceutical company laid out plans to sell $275 million in convertible subordinated notes due June 15, 2013. The company plans to use a portion of the proceeds to redeem some $165 million of its convertible subordinated notes. The company plans to use the remaining proceeds to increase funding for the commercialization of its Cubicin antibiotic and for working capital and general corporate purposes. Goldman Sachs is leading the underwriting syndicate. Shares were trading down $2.23 to $23.80. Other health care volume movers included Pfizer (PFE:NYSE) , up 3 cents to $23.61; Merck (MRK:NYSE) , up 57 cents to $33.33; Boston Scientific (BSX:NYSE) , up 18 cents to $20.50; UnitedHealth Group (UNH:NYSE) , up 69 cents to $44.02; Amgen (AMGN:Nasdaq) , up 25 cents to $67.08; Elan (ELN:NYSE ADR) , down 8 cents to $18.90; Johnson & Johnson (JNJ:NYSE) , up 16 cents to $60.01; Teva Pharmaceutical (TEVA:Nasdaq) , down 60 cents to $36.47; and Bristol-Myers Squibb (BMY:NYSE) , down 7 cents to $24.49.