Most biopharma companies, and most biopharma researchers, spend their time studying unmet medical needs and then casting about for chemicals or biologicals that have an effect on that need. Result: an approved product that saves lives or improves health. But when it comes to pain, by and large, the industry is stuck on one thing: refined, semi-synthesized or synthesized forms of opium, leading to morphine, codeine, hydrocodone, oxycodone, fentanyl and quite a few others. All of these are controlled substances (Schedule II or III under the Controlled Substances Act). And, as has been widely recognized, US society is suffering through an epidemic of prescription drug abuse, with these pain compounds the main form of abuse. (Psychoactives like alprazolam or lorazepam are fast coming up behind.)
The most widely cited—and most appalling—statistic in prescription drug abuse is that it causes the deaths of 15,000 Americans annually. One would assume that a family of drugs that wreaks such havoc could be isolated, quarantined and arguably eliminated, but of course that is not so easy. Counterpoised against restrictions of these drugs is the real medical need for pain palliatives and until recently, much of the medical profession has supported broader access to pain medicines, especially in cancer care, end-of-life treatment and chronic pain.
There is something of a countertrend occurring now: During the Congressional negotiations for the FDA Safety and Innovation Act, passed last summer, an effort was made to change the status of hydrocodone from Schedule III to the more restrictive Schedule II (where dosages, refills and prescribing practices are more rigid). That change did not pass. In the past month, an FDA panel voted to make that change administratively, but there will be several more steps before it happens, if it does. Here are some facts that were surprising, to me at least, about hydrocodone: It is the No. 1 prescribed product in the US, with 132 million prescriptions filled in 2011 (IMS Health data). According to the International Narcotics Control Board (an arm of the World Health Organization), the US consumes 99% of the hydrocodone produced in the world; in fact, its use is banned in most of Europe. And although that drug is front and center in abuse discussions, prescriptions have steadily risen in each of the past five years.
(Oxycodone is a comparable product, nationally and globally—but the US consumes 80% of that drug; also 55.4% of the world’s morphine supply. The US leads the world, either in its low resistance to pain, or its high tolerance of prescription drug abuse.)
Opiates stress the entire pharma distribution system, from manufacturer to patient. Manufacturers are negotiating a “class-wide REMS” (risk evaluation and mitigation strategy) with FDA. The Drug Enforcement Administration has been investigating—and removing the DEA licenses of—wholesalers, pharmacies, pharmacists and doctors regularly all over the country. Doctors, pharmacists and hospital workers are routinely subject to violent assault by addicts and thieves. An amazingly large number of associations, societies and advocacy groups have sprung up to address prescription drug abuse. (A key meeting* is coming up soon: the 2013 National Rx Drug Abuse Summit [Orlando, FL; April 2–4].)
There is so, so much that industry has to do. Manufacturers and distributors build DEA-validated vaults to store controlled substances (an executive at Custom Vault, a supplier of these systems, comments: “Pharmaceutical companies constantly re-evaluate vault capacity based on anticipated volume increases, and vaults are always getting bigger.”) Carriers invest in cargo-theft prevention. Wholesalers and chain pharmacies are investing in “suspicious order monitoring” systems to track ordering trends, from companies like e-SupplyLink, IntegriChain, ValueCentric and BuzzeoPDMA (a Cegedim company). States are legislating for, and then implementing, prescription drug monitoring programs (PDMPs) that aggregate individual prescription data from multiple pharmacies, to prevent “doctor shopping” for multiple prescriptions. And among healthcare providers, there is some momentum to adapt an “opioid dosing guideline,” originated at the Washington State Medical Directors Group,** that has succeeded in reducing over-prescribing and accidental deaths.
The battle lines are drawn, but this war is going to continue for a long time.