Amgen Inc. once had high hopes for a promising Parkinson’s disease treatment called GDNF that it had been nursing since the mid-1990s even featuring inspiring clips of clinical trial participants in a promotional video shown to investors early last year.
Then, suddenly, everything changed.
The Thousand Oaks biotech giant announced last fall that it would halt clinical trials and stop providing the drug to 48 trial participants, citing its ineffectiveness and evidence of potentially debilitating human side effects.
Not all trial participants agreed. Saying they were benefiting from the drug, they sued Amgen in New York and Kentucky in an unsuccessful effort to force the company to continue providing it to them.
The company said that ethical and patient safety considerations dictated its decision, but other factors might also have been at play specifically newly heightened fear of litigation amid the lawsuits over Vioxx and other pain medication.
“We don’t know what was going on in the heads of Amgen’s leadership, but it’s hard to escape the suspicion that drug companies these days have a fear of running into a Vioxx situation down the road,” said Robin Elliott, executive director of the New York-based Parkinson’s Disease Foundation.
Devastated Parkinson’s patients and their supporters suspect that GDNF fell victim of today’s more litigious environment and that is only one drug out of thousands being developed by Amgen and other companies.
Drugmakers deny they are taking risk-averse actions that keep their products out of the hands of patients. Still, they are taking note of the shifting environment. Last month, the Pharmaceutical Research and Manufacturers Association announced that it had developed a new advertising code that called for manufacturers to better balance the risk and benefits of the drugs they directly advertise to consumers.
Hakan Edstrom, president and chief operating officer at Valencia’s Mannkind Corp., said he has seen a change in expectations over the years. With its first drug candidate a powdered form of insulin administered by inhaler entering late-stage safety trials, both in-house and outside lawyers monitor each stage of the drug’s development.
“Certainly that would not have been the case 20 years ago,” said Edstrom. “You want to spend as much as possible on product development but you also have to devote much more resources to defending yourself or building legal defenses around what you do in the development stage, just in case. It can become very expensive for a company like ours.”
Proactive or reactive?
Amgen spokeswoman Mary Klem notes that “patient safety is Amgen’s first priority and continues to be a priority even after a product received FDA approval.”
Indeed, GDNF isn’t the first experimental drug that Amgen pulled during human trials. In the late 1990s the company discontinued work on two late-stage drug candidates, including a treatment for Lou Gehrig’s disease, for reasons similar to those cited for GDNF.
When Amgen decided to stop clinical trials for GDNF, Chief Executive Kevin Sharer was quoted as saying he was “heartbroken” by the drug’s apparent failure, and that stopping the study was the most difficult decision he had made since taking the helm there in 2000.
Until a few years ago, Amgen had largely avoided controversy over safety. It became the world’s largest biotech company, largely on the success of two drugs, Epogen, taken by cancer and renal failure patients to counter anemia, and Neupogen, taken by chemotherapy patients to fight infection.
At first, there was little competition and few safety questions. But the company began to feel the heat of the changed environment in the drug industry. Three years ago, reports surfaced that Eprex, a version of Epogen licensed from Amgen by Johnson & Johnson and sold in Europe, was resulting in the death of some patients.
Studies showed that a different stabilizer Johnson & Johnson used to manufacture Eprex led to an immune response that led to a severe form of anemia. A similar drug sold by Roche Holding AG caused similar fatalities. The problem caused Johnson & Johnson to add a warning to its prescribing information in 2003 and send a letter to physicians last August.
Amgen for years had discounted the possibility that Aranesp, its second generation of Epogen, could cause similar deaths. But in January it issued a letter to physicians warning that high doses of anemia drugs, including Aranesp, may be dangerous to cancer and kidney disease patients.
Jon Fisher, who manages around the $22 billion Cincinnati based Fifth Third Asset Management, a private equity fund, said he sees the actions of Amgen and other drug companies through the prism of litigation.
“The drug companies are seen as the bad guys with deep pockets,” said Fisher, whose fund holds both Merck and Amgen shares. “Companies see lawsuits as the risk of doing business these days because we live in a litigious society.”
It’s not the only time Amgen has reacted strongly to possible risk exposure.
Last February, the Food and Drug Administration demanded that the company pull a TV ad for the psoriasis treatment Enbrel because regulators considered it misleading. The ad, which showed models in bathing suits with clear, exposed skin, claimed psoriasis sufferers could get the unsightly disease “off their back” with regular injections of the drug. The FDA found that the ad minimized the risks while significantly overselling the drug’s benefits.
With Vioxx and other anti-inflammatory painkillers so heavily advertised, the industry trade group last month published new voluntary, direct-to-consumer advertising guidelines.
The guidelines suggest that companies submit ads to the FDA before they are aired, that claims be supported by “substantial evidence” and that the spots balance benefits and drawbacks, among other changes.
Amgen, after getting slapped by the FDA over Enbrel, not only signed on but went further, pledging it would not air advertisement until it received specific “pre-clearance” from the FDA.