FTC Sues Drug Makers for Oxymorphone Monopoly

By Pat Anson, PNN Editor

It was in 2017 that Endo Pharmaceuticals – under pressure from the Food and Drug Administration -- stopped selling Opana ER, an extended-release version of the opioid painkiller oxymorphone. Opana had been reformulated by Endo to make it harder to abuse, but the FDA maintained the tablets were still being crushed, liquefied and then injected by illicit drug users.

Although Opana has been off the market for nearly four years, a legal battle still rages over sales of generic oxymorphone and whether Endo conspired with another drug maker to control the market for oxymorphone.

This week the Federal Trade Commission sued Endo, Impax Laboratories, and Impax’s owner, Amneal Pharmaceuticals, alleging that a 2017 agreement between Endo and Impax violated antitrust laws by eliminating competition for oxymorphone ER.

It’s the second time the FTC filed complaints against Endo, Impax and Amneal for allegedly creating an oxymorphone monopoly.

“The agreement between Endo and Impax has eliminated the incentive for competition, which drives affordable prices,” Gail Levine, Deputy Director of the FTC’s Bureau of Competition said in a statement. “By keeping competitors off the market, the agreement lets Impax continue to charge monopoly prices while Endo and Impax split the monopoly profits.”

According to the FTC complaint, Opana ER generated nearly $160 million in revenue for Endo in 2016 and was the company’s “highest-grossing branded pain management drug.” Endo explored bringing another oxymorphone drug on the market to replace its lost revenue, but ultimately decided to partner with Impax, which had the only extended-release oxymorphone drug on the market.. Their agreement allowed Endo to share in Impax’s oxymorphone profits, as long as Endo did not bring another generic tablet on the market.

“The purpose and effect of the 2017 Agreement is to ensure that Endo, the gatekeeper to competition in the oxymorphone ER market, has every incentive to preserve Impax’s monopoly. By doing so, it eliminates any potential for oxymorphone ER competition, allowing Endo and Impax to share in the monopoly profits. As a result, patients have been denied the benefits of competition, forcing them and other purchasers to pay millions of dollars a year more for this medication,” the FTC complaint alleges.

The 2017 agreement between Endo and Impax arose from a breach of contract case relating to a patent settlement between the companies over Impax’s generic version of Opana ER, in which Endo paid Impax more than $112 million not to compete. In 2019, the FTC ruled that settlement was an illegal "pay-to-delay" agreement.  

Both Endo and Amneal deny there was any effort to create a monopoly in their 2017 agreement.

“It is Endo’s position that the Agreement had no adverse impact on actual or potential competition.  At the time of the Agreement, the U.S. Food and Drug Administration had asked Endo to withdraw reformulated Opana ER from the market for safety reasons and Endo had publicly announced its intention to comply with the FDA’s request,” Matthew Maletta, Endo’s Executive Vice President and Chief Legal Officer, said in a statement to PNN.

“Significantly, as Endo has explained to the FTC, the Company has not launched or licensed any new opioid product(s) since that time, and the FTC’s theory that Endo would do so in the current litigation environment but for the Agreement is preposterous.”

“Far from being anticompetitive, the 2017 Amendment resolved a dispute between the parties that could have kept Impax's lower-priced generic product off the market entirely,” Amneal said in a statement. “We are confident there is no unlawful restraint in the 2017 Amendment, because nothing in the agreement prevents Endo from competing, and we intend to vigorously defend against the FTC’s claims.”

The FTC decision to sue Endo and Amneal a second time was approved on a split 3 to 2 vote by the agency’s commission. The complaint seeks monetary relief and a permanent injunction to prohibit the companies from engaging in similar conduct.

Extended-released oxymorphone is approved for the treatment of moderate to severe pain.  

Drug Maker to Stop Sales of Opana ER

By Pat Anson, Editor

Endo International has agreed to voluntarily remove Opana ER from the market, one month after the Food and Drug Administration said safety risks posed by the pain medication outweigh its benefits. Opana ER is the brand name for Endo’s extended release opioid painkiller oxymorphone.

“Endo International continues to believe in the safety, efficacy, and favorable benefit-risk profile of Opana ER when used as intended, and notes that the Company has taken significant steps over the years to combat misuse and abuse,” the company said in a statement.

“Endo reiterates that neither the FDA's withdrawal request nor Endo's decision to voluntarily remove Opana ER from the market reflect a finding that the product is not safe or effective when taken as prescribed.”

If Endo had not agreed to stop Opana sales, the FDA would have taken steps to require its removal by withdrawing approval for the drug. The company said it would work with the FDA to remove Opana “in a manner that looks to minimize treatment disruption for patients” and to give patients time to consult with doctors about other alternative painkillers.

The FDA action is the first time the agency has taken steps to stop an opioid painkiller from being sold. Opana was reformulated by Endo in 2012 to make it harder to abuse, but addicts quickly discovered they could still inject it. The FDA said Opana was linked to serious outbreaks of HIV, hepatitis C and a blood clotting disorder spread by infected needles.

Next week the FDA will meet with “external thought leaders” to review the effectiveness of other painkillers made with abuse deterrent formulas, which make medications harder for addicts to crush or liquefy for snorting and injecting.

FDA commissioner Scott Gottlieb, MD, has hinted the agency could take other painkillers off the market.

“We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse,” Gottlieb said last month.

“I’m hopeful that this signals a change at FDA—and that Opana might be just the first opioid that they’ll consider taking off the market. It’s too soon to tell,” Andrew Kolodny, MD, Executive Director of Physicians for Responsible Opioid Prescribing (PROP) told Mother Jones.

Endo said it will incur a pre-tax impairment charge of $20 million in the second quarter of 2017 to write-off the remaining book value of Opana.  Sales of Opana reached nearly $159 million in 2016.

FDA Wants Opana ER Sales Stopped

By Pat Anson, Editor

The U.S. Food and Drug Administration today asked Endo Pharmaceuticals to remove Opana ER from the market, citing concerns about safety risks when the tablets are liquefied and injected. It’s the first time the agency has taken steps to stop an opioid painkiller from being sold -- and oddly it has more to do with preventing HIV and Hepatitis C than it does in preventing opioid abuse.

“We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”

Opana ER is the brand name for Endo’s extended release opioid painkiller oxymorphone. It was first approved by the FDA in 2006 for the management of moderate to severe pain.  In 2012, after numerous reports that it was being abused and sold on the black market, Opana was reformulated by Endo to make it harder for addicts to crush or liquefy.

That same year, over a dozen cases of a serious blood clotting disorder and Hepatitis C in intravenous drug users were linked to the reformulated Opana in Tennessee. But it took another five years for the FDA to act.

In March, an FDA advisory panel voted 18-8 that the benefits of reformulated Opana no longer outweighed its risks. The agency found“a significant shift in the route of abuse” from snorting to injection. Injecting Opana was associated with outbreaks of HIV, Hepatitis C and a blood clotting disorder called thrombotic thrombocytopenic purpura. All can be spread intravenously by infected needles.

“The abuse and manipulation of reformulated Opana ER by injection has resulted in a serious disease outbreak. When we determined that the product had dangerous unintended consequences, we made a decision to request its withdrawal from the market,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research. “This action will protect the public from further potential for misuse and abuse of this product.”

The FDA has requested that Endo voluntarily remove Opana from the market. Should the company refuse to do so, the agency intends to take steps to formally require its removal by withdrawing approval.

"Endo is reviewing the request and is evaluating the full range of potential options as we determine the appropriate path forward," the company said in a statement. "Despite the FDA's request to withdraw Opana ER from the market, this request does not indicate uncertainty with the product's safety or efficacy when taken as prescribed. Endo remains confident in the body of evidence established through clinical research demonstrating that Opana ER has a favorable risk-benefit profile when used as intended in appropriate patients."

According to Bloomberg, sales of Opana  reached nearly $160 million last year, about 4 percent of the company’s total revenue.

Belbuca Effective in Treating Pain Long Term

By Pat Anson, Editor

A new opioid film designed to be taken orally twice a day significantly reduces pain and the need for breakthrough pain medication in patients with moderate to severe pain, according to a new clinical study by Endo International (NASDAQ: ENDP). The results of the Phase III study were released this weekend at the International Conference on Opioids in Boston.

Belbuca is the only analgesic formulation of buprenorphine in a sublingual film that is dissolved in the mouth and absorbed through the inner lining of the cheek.

Buprenorphine is an opioid classified as a Schedule III controlled substance, which means it has lower abuse potential than Schedule II drugs, a category that includes opioids such as hydrocodone. Buprenorphine is also used to treat addiction when combined with naloxone.

Over 400 patients with moderate to severe pain took Belbuca for 48 weeks after being titrated to find the most effective dose. During long term treatment, the average daily pain score was about 3 on a scale of 0 (no pain) to 10 (worst pain imaginable).

The need for daily rescue medication to relieve breakthrough pain decreased from an average of 3 tablets to 1.1 tablets.

"Many patients living with chronic pain require long-term treatment to control their suffering, so it is important that patients have options to manage their pain," said Martin Hale, MD, Medical Director of Gold Coast Research, one of the study's investigators. "These new findings support the safety and tolerability of treatment with Belbuca across a broad range of dosage strengths.”

About half of the patients (54%) experienced some type of side effect, including nausea, constipation, headache, vomiting and upper respiratory tract infection.

Belbuca was approved by the U.S. Food and Drug Administration in October 2015 for use in patients with pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatments are inadequate.

Belbuca utilizes a drug delivery system developed by BioDelivery Sciences (NASDAQ: BDSI). Because the oral film delivers buprenorphine into the bloodstream faster than pills or skin patches, lower doses are needed to treat pain. The film contains one-tenth to one-twentieth the amount of buprenorphine as Suboxone and other products that are used to treat opioid addiction.

Belbuca is available in seven different dosages, allowing physicians to titrate Belbuca to a tolerable dose that provides pain relief with fewer side effects. According to the Healthcare Bluebook, a 75mcg, 60-day supply of Belbuca should cost about $265.

FDA Approves New Opioid Film Patch

By Pat Anson, Editor

The U.S. Food and Drug Administration has approved a new delivery system for the treatment of chronic pain – the first of its kind to use an oral film patch containing buprenorphine.

The film patch – which will be sold under the brand name Belbuca -- was jointly developed by Endo International (NASDAQ: ENDP) and BioDelivery Sciences (NASDAQ: BDSI). It’s expected to become available early next year.

image courtesy biodelivery sciences

Belbuca is designed to dissolve in the mouth, delivering buprenorphine through the inside lining of the cheek and into the bloodstream faster than conventional pills or skin patches. Buprenorphine is a weaker acting opioid that has long been used to treat both addiction and chronic pain.

“Belbuca provides a unique approach for chronic pain management, combining the proven efficacy and established safety of buprenorphine with a novel buccal film delivery system that adds convenience and flexibility," said Richard Rauck, MD, Director of Carolinas Pain Institute in Winston Salem, NC.

"For both opioid-naïve and opioid-experienced patients who require around-the-clock treatment and for whom alternative treatment options are inadequate, Belbuca offers appropriate, consistent pain relief and a low incidence of typical opioid-like side effects.”

Because the film delivers buprenorphine into the bloodstream faster than conventional methods, lower doses are needed to treat pain. Belbuca will be available in seven different dosage strengths, allowing for flexible dosing every 12 hours.

FDA approval of Belbuca was based on two Phase III studies involving over 1,500 patients with moderate to severe chronic low back pain. Patients who used Belbuca reported “statistically significant improvement” in pain relief over a 12-week period, compared to a placebo. The most common adverse reactions to Belbuca were nausea, constipation, headache, vomiting, fatigue, dizziness, somnolence, diarrhea, dry mouth, and upper respiratory tract infection.

Buprenorphine is a Schedule III controlled substance, which means it has a lower abuse potential than many other opioids. It may also be easier to get a prescription for than Schedule II drugs such as hydrocodone.

“If you’re going to use an opioid, I think based on its classification, Belbuca really does offer some significant benefits,” said Dr. Mark Sirgo, President and CEO of BioDeliversy Sciences.

“There are two areas this product will be used for. Those that are stepping up from a Motrin-like drug, a non-steroidal anti-inflammatory, that no longer controls their chronic pain. Those are good candidates for Belbuca. And in those that may already be on a Schedule II product such as Vicodon, one of the oxycodone products or morphine products, where a physician may feel more comfortable using a buprenorphine product than a Schedule II opioid."

Sirgo says Belbuca is also less likely to abused than a pill, because the film patches are difficult to grind or liquefy for snorting or injecting.