12/20/16

The Opioid Buzzard

© Andrea Izzotti | 123rf.com

The U.S. is in the midst of a health crisis from the use and abuse of opioids. Since 1999, the rate of overdose deaths from opioids—prescription pain relievers and heroin—nearly quadrupled. On an average day in the U.S. more than 650,000 opioid prescriptions are dispensed; 3,900 people begin nonmedical use of opioids; 580 people start using heroin; and 78 people die from an opioid-related overdose. Economically, there is a $20 billion cost in emergency department and inpatient care for opioid poisoning each year; and $55 billion spent on health and social costs related to prescription opioid abuse.

In order to address this opioid epidemic, the U.S. Department of Health and Human Services (HHS) launched an initiative in March of 2015 aimed at improving prescribing practices, expanding the access to and use of medication-assisted treatment and expanding the use of naloxone. So far, the Substance Abuse and Mental Health administration (SAMHSA) has awarded $10.7 million to 11 high-burden states for medication-assisted treatment (MAT). Applications were due in May of 2016 and awards were to be made to an additional 11 states. The above information and statistics were drawn from a Health and Human Services report, “The Opioid Epidemic: By the Numbers.”

Then in July of 2016, the HHS Secretary announced new rules that permit doctors licensed to dispense buprenorphine to see as many as 274 patients per year. The old limit was 100. HHS estimated that change permits as many as 70,000 more people to access buprenorphine. The former limit of 100 was seen by many as a barrier to individuals seeking to access MAT. “The rule aims to increase access to medication-assisted treatment and associated behavioral health supports for tens of thousands of people with opioid use disorders, while preventing diversion.” Clearly buprenorphine products like Suboxone are seen as a crucial element in our attempts to combat the opioid health crisis.

There are issues with this approach to treatment for the opioid crisis that I’ve addressed previously in articles such as: “The Seduction of Opioid Substitution” and “A Double-Edged Drug.” Here I want to look at how the company that brought buprenorphine treatment to market, Indivior/Reckitt Benckiser, tried to position itself as the primary service provider for buprenorphine-based MAT in the U.S. It’s kind of like a buzzard chasing off smaller scavengers from the carcass of an overdose victim. At one point, Reckitt Benckiser had 85% of the U.S. MAT market—almost all of it subsidized by taxpayers.

In 1994 Reckitt Benckiser established the Buprenorphine Business Group to develop buprenorphine as a treatment for opioid dependence. In 2000 legislation (DATA 2000) was passed in the U.S. permitting office-based treatment of opioid dependence. In 2002 the FDA approved Subutex (buprenorphine) and Suboxone (buprenorphine and naloxone) for the treatment of opioid dependence in the U.S. These products came to market in 2003. In 2007 the initial cap of 30 patients was raised to 100 for physicians with at least one year’s experience with buprenorphine. That same year Reckitt Benckiser acquired the rights for the sublingual film version of Suboxone from MonoSol Rx. Then in 2010 Suboxone sublingual film was launched in the U.S. Subutex tablets were discontinued in 2011; and Suboxone tablets met the same fate in 2012. In December of 2014, Reckitt Benckiser spun its specialty pharmaceutical company into a separate business and Indivior was born.

This history was taken directly from the Indivior website, where the company estimated they had treated 5 million individuals in the U.S. with Suboxone film and tablets and Subutex tablets. Here are some additional facts to add to the above timeline from a 2013 article, “Pharma Gamemanship.”

Reckitt Benckiser (RB) knew it only had patent exclusivity for their buprenorphine products until 2009. But they had a plan to circumvent the pending loss. As noted above, they acquired the rights for the sublingual film version of Suboxone in 2008. In October of 2008 they submitted a New Drug Application to the FDA for the film version of Suboxone; and it was approved in August of 2010. Reckitt Benckiser has patent exclusivity on the newer film version until 2023.

In their 2011 annual report (no longer retrievable from its website), RB indicated to their shareholders that competition from generics could take up to 80% of the revenue and profit from the U.S. Suboxone market. But they expected “that the Suboxone film will help to mitigate the impact.” In September of 2012 RB announced that they were voluntarily withdrawing Suboxone tablets from the market because of data they had received from the U.S. Poison Control Centers suggesting there were higher rates of pediatric overdose on the tablet formulation than the film version. They said they would take the tablet form off the market to “protect public health and safety.”

The very same day RB filed a “Citizen’s Petition” with the FDA calling for the agency to postpone the approval of generic version of Suboxone in the interests of public safety. Reporting for The Daily Beast, Christopher Moraff said the “data” they based their withdrawal of Suboxone tablets on was a single study RB had paid for itself. RB reportedly said the study demonstrated the risk factor for accidental ingestion was eight times higher in bottled tablets than for the individually packaged film. Yet its own data told a different story.

Compared to the more than 20,000 deaths in 2012 from prescription opiates and heroin, pediatric poisoning from Suboxone was far from a public health crisis. A preliminary study commissioned by Reckitt Benckiser found just 46 cases of serious injury or death out of more than 2,200 accidental pediatric exposures to Suboxone tablets between 2010 and 2012—which researchers described as not significantly different from poisonings from the film.

The FDA thought the RB study was inconclusive and did not demonstrate any difference in the safety profile or abuse potential of the two formulations. They said the study was poorly designed and conducted. “Reckitt’s own actions also undermine, to some extent, its claims with respect to the severity of this safety issue.” Despite the first report of pediatric death in June of 2010, RB continued marketing the tablets in multi-dose containers for two more years. And it continues to sell them throughout Europe, where Suboxone tablets are still under patent.

In June 2013 the FTC opened an investigation into whether Reckitt Benckiser abused public regulatory processes and fought for nearly two years to obtain more than 20,000 documents the company was fighting to withhold. That case is ongoing. In December of that year, federal agents raided Reckitt Benckiser’s West Virginia offices after the Department of Justice launched a criminal probe into the company’s Suboxone business. That investigation continues.

Public Citizen said that few, if any, companies went as far as RB to pre-emptively withdraw an off-patent drug from the market to make room for a newly patented successor. A year before the withdrawal of the tablets from the market, RB stated in its 2011 report that its goal was to convert as many tablet users as possible to the film version.

To this end, the company initiated a marketing campaign to persuade physicians to switch patients from the tablet to film form. It also employed more direct tactics to complement the marketing push, raising the price of the tablets to levels higher than the film versions. As a result of these efforts, tablet sales fell 19 percent between August 2011 and August 2012, while sales of Suboxone film doubled during the same period. By September 2012, the film version had captured 70 percent of the Suboxone market, clearing the way for the announcement of the withdrawal of the tablets that month.

So it should come as no surprise that a lawsuit has been filed by 35 states and the District of Columbia alleging that Indivior violated antitrust laws by trying to extend its monopoly over Suboxone. Reporting for CNN, Susan Scutti said the lawsuit charges that Indivior/RB and MonoSol Rx “conspired to block generic competitors for Suboxone by switching the drug from a tablet to a dissolving film.” A September 23, 2016 press release on the Indivior website said: “The Company intends to continue to vigorously defend its position.”

The International-Dictionary.com said there are two meanings for the word “buzzard.” The first one is zoological, referring to a bird of prey of the hawk family. The second meaning is “a blockhead; a dunce.” A quote attributed to Goldsmith reads: “It is common, to a proverb, to call one who can not be taught, or who continues obstinately ignorant, a buzzard.” It seems to me that either sense can be applied to Reckitt Benckiser and Indivior.