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Merck Dumps Heplisav in Wake of Regulatory Issues(BioWorld Today Via Acquire Media NewsEdge) Good Fit for GSK? Nine months after a case of vasculitis derailed Dynavax Technologies Corp.'s development of hepatitis B vaccine Heplisav, Merck & Co. Inc. bailed out of its partnership on the product. Dynavax had licensed Heplisav to Merck last year in a deal worth $31.5 million up front and as much as $105 million in milestone payments. Although no money-triggering milestones had been achieved, Merck was reimbursing most of the development costs for Heplisav, including hepatitis B virus (HBV) prevention trials in healthy adults and in end-stage renal disease (ESRD) patients. (See BioWorld Today, Nov. 2, 2007.) The trouble started last March, when the FDA placed a clinical hold on Heplisav after a patient in its Phase III healthy adult study began showing symptoms of vasculitis, an autoimmune condition also known as Wegener's granulomatosis. At the time, Dynavax President and CEO Dino Dina said he did not anticipate a connection between Heplisav and the vasculitis case, even though the condition has cropped up with other vaccines. (See BioWorld Today, March 19, 2008.) The clinical hold halted progress with Dynavax's Phase II trial in ESRD and consistency studies needed for the healthy adult biologics license application. Yet patient treatment in the Phase III healthy adult trial was completed before the hold, and data released in August showed that the vaccine met its primary endpoint of inducing a noninferior antibody response (95 percent) compared to GlaxoSmithKline plc's marketed hepatitis B vaccine, Engerix-B (81.1 percent). (See BioWorld Today, Aug. 7, 2008.) Dynavax and Merck submitted a complete response to the FDA in September, hoping to see the clinical hold lifted. But the agency responded in October that the balance of risk vs. potential benefit no longer favored continued clinical evaluation of Heplisav in healthy adults. Shares of Dynavax plummeted 80 percent. Dynavax's vice president and chief business officer, Michael Ostrach, told BioWorld Today it is "disconcerting" that the FDA weighed a single adverse event more heavily than the benefits Heplisav showed in its Phase III trial. But he noted that Dynavax has not given up on the vaccine, adding that "we have a number of discussions about that ahead of us." The company also plans to discuss the use of Heplisav in ESRD with the FDA. The agency indicated that the risk-vs.-benefit profile of the vaccine may be more acceptable in this patient group and requested additional information before considering further clinical studies. Dynavax said it hopes to have additional insight into the regulatory path for Heplisav in the first quarter of 2009. Ostrach also noted that there are no clinical holds on the product outside of the U.S., and Dynavax is "engaged in the process" of working out an ex-U.S. regulatory path. He said the ex-U.S. market in healthy adults and the worldwide market in ESRD comprise 70 percent of the potential value for the product. Even so, Merck terminated its partnership for Heplisav and handed all rights back to Dynavax. The Berkeley, Calif.-based biotech's shares (NASDAQ:DVAX) fell 47 cents, or 30.5 percent, to close at $1.07 on Friday. Heplisav combines HBV surface antigen with Dynavax's immunostimulatory sequence (ISS) technology, which is designed to stimulate an innate immune response by targeting Toll-like receptor (TLR) 9. The product is by no means the first TLR agonist to suffer a setback. Dynavax's own TLR9 allergy drug Tolamba failed two Phase III trials, Anadys Pharmaceuticals Inc. had to suspend dosing of its TLR7 drug for HCV and Coley Pharmaceutical Group Inc. suspended development of its TLR9 HCV drug and halted Phase III trials of its TLR9 cancer drug. (See BioWorld Today, June 27, 2006, Jan. 24, 2007, June 21, 2007, and May 19, 2008.) Yet Ostrach argued that "a failure of our competitors or even one of our programs" shouldn't be viewed as an indictment of the field or technology. "This is the drug business . . . the hit rate is about one in 20," he said. Dynavax remains confident in Heplisav and, if the regulatory feedback it receives is favorable, it may seek a new partner. One pharma that may perk up its ears at the Heplisav opportunity is London-based GlaxoSmithKline. In addition to the fact that Heplisav performed well against GSK's Engerix-B in Phase III, the company became "quite familiar" with the Heplisav program in the discussions that preceded the Merck partnership, Ostrach said. Additionally, GSK signed a potential $810 million Toll-like receptor antagonist deal with Dynavax earlier last week. (See BioWorld Today, Dec. 18, 2008.) Ostrach said he can't speak for GSK, but that Dynavax's re-acquisition of full rights to the Heplisav program is "certainly an opportunity" and "may well be very attractive" for GSK. Dynavax is well funded as it considers new partnering options. Ostrach said the company will have $65 million in cash, equivalents and marketable securities at the end of the year - enough to last more than two years. n ? ? Copyright ? 2008 Thomson BioWorld, All Rights Reserved. |