Backed by a U.S. campaign to slow abuse of prescription painkillers, drugmakers are devising new forms of the medicines that don’t lead to misuse and new products that treat dependency in a bid to change the face of a $9.4 billion market.
Orexo AB is awaiting a July 6 U.S. ruling on a drug that blocks opiate receptors in the nervous system, potentially lessening addict dependence. Nektar Therapeutics on June 19 announced positive study results on an experimental medicine designed to enter the brain slowly, reducing the euphoria that can lead to addiction. And in April, the U.S. barred copies of the original form of OxyContin after Purdue Pharma LP proved its crush-resistant version made the therapy less valuable to addicts on the street.
Abuse of opioid painkillers killed more people in 2010 than cocaine and heroin combined. The epidemic has spurred U.S. legislation seeking to ban drugs that fail to resist tampering, amid a push by the Food and Drug Administration to encourage treatments that are less likely to become addictive.
“We are not wedded to any one way or the other” to stop the abuse, Douglas Throckmorton, deputy director for regulatory programs at the FDA, said in a telephone interview. “What we want is abuse-deterrent formulations that work. We know how important this is.”
The FDA isn’t the only U.S. agency involved in the drive to slow the abuse epidemic. The Drug Enforcement Agency on June 11 fined Walgreen Co., the largest U.S. drugstore chain, $80 million after a probe into whether it violated rules governing the distribution of the pills.
The number of women who died from an overdose of prescription painkillers jumped almost fivefold from 1999 to 2010, the Centers for Disease Control and Prevention said in a briefing today. The deaths totaled almost 48,000.
“It’s getting worse, and it’s getting worse quickly,” CDC director Thomas Frieden said on a conference call, adding that pain medicine abuse “has skyrocketed in the past decade.”
Painkiller abuse also has driven up the cost of insurance claims, a trend that the industry has been studying, said Robert Benmosche, chief executive officer of New York-based American International Group Inc., one of the largest U.S. providers of workers’ compensation coverage.
“People are desperate for their painkillers, and there was no algorithm in process for us to deal with people who we saw that were abusing that,” Benmosche said in a June 4 presentation. The insurer has been evaluating data with Johns Hopkins University in Baltimore as part of an effort to help “drive people back to work,” he said.
OxyContin sales made up about $2.81 billion of the $9.38 billion U.S. market for prescription painkillers in 2012, according to IMS Health Inc., a health-care data provider based in Danbury, Connecticut.
The FDA decision banning generic-drug makers from copying the original form of OxyContin was critical to the fight against the epidemic, said U.S. Representative Bill Keating, a Massachusetts Democrat who is sponsoring legislation designed to block any new drug, including generics, lacking tamper-resistant properties.
Without that FDA ruling in support of Purdue’s OxyContin reformulation, generic-drug makers “would’ve been going forward with a whole new supply of drugs that were dangerous and cheaper, and undoubtedly would have resulted with a geometric increase of deaths,” Keating said in a telephone interview.
“In Massachusetts, almost two people a day die from prescription drug overdose,” he said. “In some parts of the country like Appalachia and Kentucky, it’s so pronounced that 10 percent of babies are born addicted.”
In a January draft guidance, the FDA outlined several strategies to formulate new treatments and to make existing opioid analgesics less susceptible to recreational abuse. A drugmaker can slow the release of the active ingredient into the bloodstream, decreasing the initial rush in favor of longer effectiveness. Still, recreational users can crush the pills before snorting or injecting them to create a concentrated high.
To combat this manipulation, a pill can be fitted with physical features that make it harder to grind up and ingest.
Endo Health Solutions Inc.’s Opana, for instance, was fitted with a harder shell to hinder crushing. Purdue’s reformulation of OxyContin makes it congeal when crushed, ruining the powdery consistency ideal for snorting or injection.
The OxyContin reformulation has been successful in diminishing street appeal, according to research that shows the new form sells for 28 percent less on the black market than the original formula. During a November pharmacy robbery in Cambridge, Massachusetts, the assailant refused to accept OxyContin -- once the gold standard in prescription painkiller abuse -- and instead demanded methadone and Opana.
Drugmakers could also introduce chemical combinations into the pill itself that would neutralize the ability to ingest it in non-prescribed manners. King Pharmaceuticals Inc. marketed a medicine under the brand name Embeda that combined morphine with an inner core of naltrexone, an opioid receptor antagonist. The core, which negates the potency of the morphine, would only release when the pill was crushed. King withdrew the therapy from the market in 2011.
Alternatively, pills that induce an unpleasant sensation can discourage overuse or alternative administration. Ingredients such as niacin or capsaicin, found in chili peppers, would make overindulgence undesirable.
“Putting other things in the opiate that make it unattractive and unpleasant to use could create abuse deterrent properties,” the FDA’s Throckmorton said. “Putting soap in a product makes it more unpleasant to put it in your nose and snort it up.”
Some activists say the fight against abuse may make cheap medications scarcer.
“The primary reason the FDA needs to act is patient safety, but the market for abuse-deterrent medication is very fragile,” said Michael C. Barnes, executive director of the Center for Lawful Access and Abuse Deterrence in Washington. “If the FDA doesn’t make the right decision, it could collapse.”
Striking a balance between the conflicting need for opioids with advanced deterrent properties and for a robust market for generic painkillers is a challenge for government regulators.
In the past three months, the makers of OxyContin and Opana asked the FDA to rule that the previous formulations of their drugs had been taken off the market for safety or effectiveness reasons, thereby making them ineligible for reproduction in the generic market. In April, the regulator agreed with Stamford, Connecticut-based Purdue on its OxyContin, preventing companies like Teva Pharmaceutical Industries Ltd. and Impax Laboratories Inc. from making copies.
The following month, the FDA rejected a similar request for Chadds Ford, Pennsylvania-based Endo’s Opana ER. The agency decided that the increase in abuse deterrence in the new formula was insufficient to block the generic.
“Reformulated Opana ER can be readily prepared for injection,” the FDA said in the May ruling. “It also appears that reformulated Opana ER can be prepared for snorting using commonly available tools and methods.”
Though the new pill was harder to crush than the original, the agency found it could still be cut, ground, or chewed. At the time of the decision, Endo announced that the generic competition may reduce sales this year by as much as $120 million.
“We were surprised by the decision but remain committed as a company to fight opioid abuse,” Endo spokesman Blaine Davis said in a telephone interview. “There is not only a financial impact but also a patient impact from having a more-abusable product in the market.”