Bristol-Myers Squibb says it hasn’t given up on Pargluva. 

    In late October, after the FDA said it wanted additional information about the drug’s cardiovascular risks, the company said it would walk away from the new PPAR inhibitor for type-II diabetes. But on Monday, the BMS insisted that it remains in serious negotiations with Merck, its partner in Pargluva (muraglitazar) development. 

    “It’s only been a month since we released our statement, and the status hasn’t really changed since then,” said Bristol-Myers spokesperson David Rosen, referring to the joint statement Bristol-Myers issued with Merck. “We are determining what is going to be the path going forward, but it’s too soon to determine what the final outcome is going to be based on all of our options,” Rosen added.

    But some analysts wonder if the project can still go forward. They say Pargluva was a bad bet from the beginning.

    “We had written a couple of reports on Pargluva before the FDA advisory committee came out,” said Barbara Ryan, managing director of Deutsche Bank, who predicted in a July interview with PharmExec that FDA would not approve the drug. “There were potentially worrisome liabilities on the cardiovascular side,” Ryan said in July.

    However, just a few months ago, it looked as though FDA would approve the drug. On September 9, FDA’s Endocrinologic and Metabolic Drugs Advisory Committee gave Pargluva an 8-1 recommendation for approval. On October 18, both companies received an “approvable letter.” 

    But in response to the approvable letter, the Journal of the American Medical Association rushed into print with a study suggesting that Pargluva had links to heart attacks and strokes. Conducted by researchers at the Cleveland Clinic and co-authored by Dr. Steven E. Nissen, the study provoked comparisons with Vioxx, Merck’s withdrawn COX-2 painkiller.

    Pargluva, an investigational oral medication, would have become the first marketed agent in a new class of compounds called glitazars. A dual peroxisome proliferators-activated receptor (PPAR) alpha/gamma agonist, the drug reduces plasma glucose and triglyceride levels while increasing the “good” cholesterol levels for type-II diabetics. 

    Then, instead of issuing final approval, FDA said it wanted more information about Pargluva’s cardiac risks.  Rather than pursue additional studies, which Deutsche Bank’s Ryan said would cost up to $100 million, the companies said they would abandon the drug.  

    The announcement couldn’t have come at a more inconvenient time for Merck, still under siege after the withdrawal of Vioxx. But Pargluva’s failure dealt an even more resounding blow to BMS, who needed Pargluva to counter a recent accounting scandal that cost the company hundreds of millions of dollars in federal penalties and civil settlements.

    “It remains a mystery to me why Merck even signed the deal in the first place,” said Ryan.  “It’s a bigger deal for Bristol-Myers because they were counting on [the success of Pargluva] financially. It’s a big blow for Bristol because they have not had growth for many years and they still need to demonstrate that they can produce a successful drug.”

Articles

Pargluva was a bad bet from early on. Analysts say so. Can BMS still save face?

What Really Happened to Pargluva

It’s been a big month for animal activists. 

    On October 27, a bill was introduced in the Senate that declares animal activists to be terrorists. Some observers may have found the proposed legislation extreme. 

    But on November 13, Jerry Vlasak, MD, a spokesman for the Animal Liberation Front (ALF), appeared on 60 Minutes and argued that it would be morally justifiable to kill a researcher who “tortures animals for a living or for profit and who won’t stop when they’re asked to.” 

    On Monday, PharmExec called Vlasak, a Los Angeles physician, and asked about his televised remarks. He did not recant. 

    “I said I thought it was morally justifiable to use violence if that was the only way it would stop,” Vlasak says. “Just like it was morally justifiable for Nelson Mandela to use violence when he fought against apartheid in South Africa; just like it was morally justifiable for John Brown to use violence when he fought against slavery in this country.”

    No one has died at the hands of animal-rights extremists, but a rising number of attacks on persons and property at research facilities suggest that there is more to Vlasak’s remarks than idle rhetoric. The National Association of Biomedical Research counted 560 incidents involving animal rights activists, ranging from stolen rabbits to vandalism, death threats and assault, since 1981. 

    “With the advent of the Internet, the attacks have become far more sophisticated, with more people involved because it’s harder to trace them,” says Frankie Trull, the founder and president of NABR. Most alarmingly, Trull says, the practice of targeting individuals with threats, identity theft, and verbal and physical abuse has “definitely escalated in the late 90s, and in this decade there’s been a dramatic escalation in all kinds of approaches.” Meanwhile, the FBI identified ALF and a spin-off group, the Earth Liberation Front, as the country’s most worrisome domestic terrorist threats. John Lewis, Deputy Assistant Director for Counterterrorism at the FBI, said the agency is investigating more than 150 cases of eco-terrorism. 

Many of these attacks were directed at pharma research facilities. In addition, animal rights groups have carried out several grassroots campaigns to convince the public that animal research is immoral and unjustifiable. All the while, pharma has remained oddly silent.

    “The pharmaceutical industry has a lot of issues they’re dealing with right now, but this needs to be viewed as one of their top priorities,” Trull says. “And that means they need to put their considerable intelligence and resources behind addressing this issue.”

    Trull suggests a public relations campaign to teach people the benefits of animal research. The message, if directed at schoolchildren, may help keep scientifically oriented youngsters from deflecting to other areas of academia because they get the wrong idea about biomedical research.

    “I think for a long time the industry has operated under the assumption that if we didn’t pay attention to [animal rights extremism], it would just go away,” says John Gallagher, director of corporate communications at Chiron. “And I think there’s been a growing awareness over the past several months that it’s never going to go away. If anything, it’s only ever going to get worse.”

    Chiron has dealt head-on with animal rights extremism, in large because the company was forced to when two homemade bombs, delivered by members from Stop Huntingdon Animal Cruelty (SHAC), which has harassed the UK-based company Huntingdon Life Sciences and other companies that do business with Huntingdon since 1999, went off on Chiron’s California campus on August 28, 2003. No one was hurt, but the bombing spurred Chiron to take a proactive approach against zealous activists. The company placed court injunctions on SHAC in 2004 and haven’t had problems with them since.

    “I think everyone’s aware of what happened to Chiron because of the pipe bombings on campus and the really severe level of harassment our employees underwent,” Gallagher says. “But my message consistently has been over the last two years that this is not about Chiron. This is about the entire industry. What happened at Chiron can happen anywhere.”

Trull, who labels the problem of animal rights extremism as “huge,” fears that continual pressure from activists will create a chilling environment for biomedical research. “If this escalates in the U.S. and the climate becomes nonconductive to research, then the research will not stop – it will just move out of the country.”

    Congress has taken note. On October 27, Sen. James Inhofe (R-Okla.) introduced a bill called the Animal Enterprise Terrorism Act, which would close up loopholes in 1992’s Animal Enterprise Protection Act by extending federal protection from research facilities to the people themselves. The act – which is unlikely to be passed this year due to time constraints – would make it a federal crime to disrupt animal research. 

    It’s a good first step, many within the pharmaceutical industry agree. Even Michael Markarian, the executive vice president of the Humane Society of the United States (HSUS), says, “We agree with Sen. Inhofe and other members of Congress that any violent activity in the name of a cause is absolutely wrong and inexcusable.” But some question whether the law targets the crux of the disagreement between pharma and activists.

    “I think the legislation won’t do anything for anybody who’s concerned about the tactics that are [the] underlying [reasons for] the legislation,” says Jeff Kerr, general counsel for People for the Ethical Treatment of Animals (PeTA). “The only thing that’s going to be effective is for the pharmaceutical industry and others involved in animal testing to move away from animal testing.” That means stopping all animal research, Kerr explains.

    It’s not something that’s about to happen anytime soon. Not counting mice, rats and birds – animals not covered under the Animal Welfare Act – the U.S. used about 1.1 million animals for research in 2004, according to a report produced by Animal Care, a branch of the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service.

“Animal research is absolutely necessary, and I think every pharmaceutical executive will understand that,” says Jacquie Calnan, president of Americans for Medical Progress, a non-profit organization designed to promote biomedical research. Calnan maintains that animal rights extremists have not curbed animal research, but she concedes that pharma has neglected its responsibility to foster research and growth.

    Noting that animal-activism organizations such as PeTA and the HSUS outspend the research community 100 to 1 for public relations, Calnan calls on pharma to mount a public relations campaign defending animal research. “We need to have PhARMA (Pharmaceutical Research and Manufacturers of America) work with us, we need to have individual companies work with us in pursuing policy and in pursuing public affairs programs that are really going to reach out,” Calnan says.

    “It’s no longer time for ostriches. We’ve got to be involved in outreach, or the activists are going to prevail.”

Animal-rights activists call for attacks on testing facilities. Congress calls activists terrorists. Industry leaders propose a response.

Pharmaceutical Executive-11-22-2005

What Really Happened to Pargluva

Animal Rights Activists Create PR Crisis