Pharma Gamesmanship in the Booming Business of Addiction Therapeutics: the Case of Suboxone

Editor’s Note: Points welcomes another new guest blogger to the ranks today. Kimberly Sue is an M.D.-Ph.D. candidate in medical anthropology at Harvard, doing ethnographic fieldwork with opiate-addicted women. Below, Kim details some very recent developments in the ways pharma companies invoke societal values around drugs in order to manage their market share, and discusses how the outcomes are likely to affect people in treatment.

Pharmaceutical companies and opiates have a complicated, intertwined history. Analgesia was and continues to be a big business as well as an ongoing medical conundrum. Opiates, as we know, are wildly popular analgesics. Yet when did opiates specifically indicated for treating addiction become such a big business, a lucrative niche market inciting pharmaceutical companies to aggressive industry maneuvers? As Penn professors John Kimberly and Thomas McLellan wrote in a 2006 article on the substance abuse treatment industry, “Pharmaceutical companies that, not long ago, refused to allow the use of even their discarded medications for clinical research in addiction now invest hundreds of millions of dollars in the marketing and sales of approved addiction medications.”

Does this say something about the changing cultural attitudes towards addiction—that pharmaceutical companies are no longer afraid of being branded as making drugs for drug addicts—or does it simply speak to the enormous profits to be had?

The re-branding of addiction as a chronic, relapsing, and remitting disease led by the National Institute on Drug Abuse in the 1990s, as well as the increasingly large numbers of opiate-addicted patients (ironically in large part due to the aggressive marketing and widespread availability of prescription opioid medications such as Percocet and Oxycontin), laid the groundwork for pharmaceutical companies to become further invested in the treatment of opiate addiction. The pharmaceutical industry was well aware of the implications that such an epistemological shift could bring: chronic diseases necessitate lifelong medical maintenance and constant vigilance, often with “drugs for life,” as Joseph Dumit’s new book calls the paradigm. Advocates of the lifetime opiate maintenance model—primarily regarding methadone—argued that it was parallel to diabetics needing their insulin.

The pharmaceutical division of a British multinational corporation, Reckitt Benckiser, got in on the ground floor. They have reaped significant profits ($1.3 billion in the US in 2011) off an opiate maintenance medication called Suboxone (buprenorphine-naloxone). Yet Reckitt wasn’t always so keen on getting into the addiction business, as Nancy Campbell and Anne Lovell have summarized in a recent article. Buprenorphine had already been approved as an analgesic in injectable and sublingual tablet forms in 26 countries. It was increasingly being used “off-label” for the treatment of opiate addiction, as Lovell noted in 2006 was the case in France. Campbell and Lovell describe Reckitt’s initial reluctance to re-brand the drug as one specifically for addiction, attributing it to “a more general attitude among pharmaceutical companies that analgesic might, as Bigelow put it, be ‘tainted’ in the eyes of prescribers and pain patients if also used for addiction” (134).

Buprenorphine is distinct from the other approved opiate maintenance counterpart, methadone, in several key ways. First, it is a partial agonist at the mu opiate receptor in the brain, not a full agonist like methadone. This means it is relatively safer than methadone, with less potential for respiratory depression and overdose. Second, Reckitt manufactured buprenorphine in combination with a full antagonist naltrexone naloxone and marketed the combination as Suboxone (the buprenorphine-only drug is called Subutex). Combining buprenorphine with naltrexone naloxone was meant to guard against people “abusing” the medication by crushing up the tablet and injecting it, since the naltrexone naloxone would become active if injected, creating unpleasant withdrawal symptoms in opioid-tolerant patients.

Eventually, Reckitt brought Subutex and Suboxone to market with part of the costs of development absorbed by NIDA “to ease the burden to Reckitts” (Campbell and Lovell 2012: 135). They note that Reckitt had also obtained “orphan drug status” using the Cost Recovery principle “that the company risked not recuperating what it invested” given relatively high manufacturing costs, even though the size of the target market was greater than the 200,000 potential patients for so-called “orphan” drugs. This status resulted in seven years of patent exclusivity. The Drug Abuse Treatment Act passed in 2000 classified Suboxone as a Schedule 3 drug that could be prescribed in an outpatient physician’s office.

Suboxone quickly became a blockbuster. Private physicians could prescribe it for patients at weekly or even monthly intervals, as opposed to the methadone clinic’s daily administration, semi-public dispensaries and intense stigma. Providers could not keep up with the demand; the maximum patient limit for providers was increased from 30 to 100 patients in 2006. There are ongoing lobbies for nurse practitioners and physician assistants to be able to prescribe it to help address the demand, since these providers are already capable of prescribing even stronger drugs like methadone and oxycodone.

Reckitt Benckiser girded themselves for the expiration of their exclusivity rights in 2009 by preparing a new formulation of suboxone. They submitted a New Drug Application to the FDA for a sublingual film version of suboxone in October of 2008 (it was approved in August 2010, with patent exclusivity until 2023). Reckitt made it clear to their shareholders in their 2011 annual report that competition from generics could take “up to 80% of the revenue and profit of the Suboxone tablet business in the US,” but added that “the Group expects that the Suboxone film will help to mitigate the impact.”

In September 2012, Reckitt Benckiser announced in a press release that they were voluntarily withdrawing the tablet formulation of suboxone from the market given the results of “specially commissioned data” that they had received from the U.S. Poison Control Centers indicating higher rates of pediatric overdose on the tablet formulation than the film version. As Reckitt-Benckiser wrote, “This is the first report provided to the company with conclusive outcomes since a preliminary review in early 2012 that showed a noticeable numerical trend but did not provide enough data points to make a statistical analysis.” They would take the tablet form off the market in the next six months in order to “protect public health and safety.”

Ed Silverman, in an article at Forbes.com, noted that Reckitt was manipulating the cost of the tablet to encourage insurers to switch patients over to the film. According to his data, Reckitt raised the price of the bottle of 30 tablets from $140 to $161.70 for the 2 mg dose and from $252 to $289.80 for the 8 mg dose, while the film version cost $117.85 for 30 2 mg films and $211.15 for the 8 mg version. They also offered a $45 monthly subsidy (Bloomberg reported it as a “Coke-style coupon”) for a patient’s typical $50 co-pay for the film. Within six months of the introduction of the film, 40% of patients had been switched over to this new formulation, and by the end of 2012, it was 64%.

Hours after announcing their plan to take the tablets off the market, Reckitt announced in a press release that they had filed a “citizen’s petition” urging the FDA to “require all manufacturers of buprenorphine-containing products for the treatment of opioid dependence to implement national public health safeguards involving pediatric exposure educational campaigns and child resistant, unit-dosed packaging to reduce the risk of pediatric exposure.” They asked the FDA to reject any new drug applications for generic suboxone tablets.

Several makers of generics filed suit against Reckitt. In one suit filed in December 2012, Burlington Drug Company alleged the “unlawful exclusion of competition from the market” in violation of the 1984 Hatch-Waxman Act, citing a “product hopping” scheme. They argued that the film version “offers no additional benefit to consumers but has effectively prevented generic competition.” Furthermore, they pointed out that Reckitt did not offer “Suboxone Tablets in unit-dose packaging in the United States as it does with Suboxone Film, even though Reckitt offers the tablet product in unit-dose packaging in other countries.” They claimed that a generic would have been on the market almost a year earlier if not for Reckitt’s assorted actions.

Reckitt, of course, is not alone in its efforts to maintain market share. It is extremely common for pharmaceutical companies to use minor innovations, such as slightly altering the drug delivery mechanism, the method of administration, etc., in order to extend the life of their brand-name drugs or obtain new patents. For example, the pharmaceutical companies behind Oxycontin and Opana, Purdue and Endo, have released versions of their long-acting narcotics that they claim are more resistant to being crushed and melted; and they sought to block generic versions of their long acting narcotic pills that do not have similar “tamper-resistant designs.” Like Reckitt, they are in the business of addiction medicine and can therefore explicitly market these maneuvers under the guise of “public health.”

Last week, the FDA issued its response to Reckitt’s citizen petition, approving two generic versions of suboxone to Amneal and Actavis pharmaceuticals. The FDA ruling noted that “although child resistant unit-dose packaging could provide additional deterrence to accidental pediatric exposure, many products which are potentially harmful to children are distributed without unit-dose packaging” (more than 75,000 pediatric poisoning cases of acetaminophen alone were reported to the Poison Control Centers in 1997). The FDA furthermore noted that Reckitt had not withdrawn the drug from the market even though they had hyped such significant safety risks to children.

The FDA called out Reckitt for its various schemes, referring the matter to the Federal Trade Commission “to investigate and address anticompetitive business practices.” As Janet Woodcock, the Director of the FDA Center for Drug Evaluation and Research, wrote in the ruling, “The timing of Reckitt’s September 2012 announcement that it would discontinue marketing of the tablet product because of pediatric exposure issues, given its close alignment with the period in which generic competition for this product was expected to begin, cannot be ignored.”

What does all this pharmaceutical maneuvering mean for patients and providers? From my ongoing ethnographic fieldwork in a suboxone clinic in Boston, I have observed that having to switch some of the patients to films generated substantial amounts of paperwork and confusion. MassHealth — Massachusetts’s Medicaid program — delayed approving the film versions without prior authorization until last week. While most of the patients in the clinic are covered by MassHealth, most other insurance companies had switched to the film version. Some of those who were switched suffered from disruptions in coverage and access. And when these patients have disruption in access to suboxone, unlike other medications they might also take, they risk relapsing to heroin. Many also report disliking the film version, saying that it didn’t seem to work as well as the pill. They will most likely have to be transitioned back to the tablet once generics become available.

Reckitt continues to look for greener pastures, including trying to develop an injectable, long-acting depot version of buprenorphine (they also just hired a veteran of SAMSHA to help them navigate the federal regulations). Their story is testament to the new pharmaceutical economies built up around managing the poor and the sick. It also speaks to the booming business of addiction treatment and the increasingly larger part that Big Pharma wants to play in shaping and legislating notions of risk, safety, and public health. Would this situation have been possible if Reckitt had not been able to play on the unique cultural and moral attitudes that our country has towards drug addiction, such as the fear of children overdosing on drugs meant for drug addicts?