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Purdue, maker of the painkiller OxyContin, has won dismissals in over 400 personal injury lawsuits related to the medication, has settled product liability cases involving the drug without disclosing the terms, and has defeated more than ten class actions suits brought against it over the painkiller, but has never gone to trial on a case of OxyContin abuse.
Purdue stands accused of actions that helped create widespread addiction to OxyContin, known in rural America as “Hillbilly Heroin", in a civil suit filed by the state of Kentucky. The company has already lost initial procedural decisions and may be facing a $1 billion judgment plus potential punitive damages and pre- and post-judgment interest, based on accusations leveled against it by the state.
The Kentucky civil suit claims that Purdue trained its sales force to falsely depict OxyContin as difficult to abuse, even though the company’s own study found that most of the active ingredient could be extracted from a tablet by simply crushing it. Addicts quickly discovered that they could get high from a single pill, which because of its timed-release feature, contained much more pain-relief medication than older painkillers. Crushing it not only defeated the time-release system, but also enabled abusers to snort or inject the drug for an immediate and intense high.
According to court documents, many OxyContin addicts went on crime sprees to feed their habits and ended up in jail, in public treatment facilities, or dead from overdoses. The claims against the company include Medicaid fraud, false advertising, and unjust enrichment, but Purdue denies them all.
Kentucky, along with Tennessee and West Virginia, is among the top five states for painkiller prescriptions per 100 people, with a rate of use twice that of New York and New Jersey. While Purdue has spent six years trying to get the case moved out of Pike County, Kentucky because the drug maker says it can’t get a fair trial there, Kentucky Attorney General Jack Conway has stated that Purdue can avoid a trial in Kentucky only by making a “very, very significant” settlement offer, and he intends to hold the company accountable.
Remi has said 8months for partnership so this news at the soonest would be after filing the NDA though given Remoxy past with FDA likely after approval.
What we need is an update if data has been transferred & does it support filing an response to the last CRL.
PFE executives no doubt got a brief on all trial results this brief is what we need.
If data supports refiling I would say other Pain programs could move forward as we'll.
Source: Seeking Alpha 12/3/14
Five publicly traded companies have at one time sold abuse deterrent painkillers in the U.S. and should be attracted by the $2.5 billion gained by rival Purdue Pharma's Oxycontin.
Pain medication specialist Mallinckrodt is already under contract to make Remoxy and is the most sensible option.
Alternatives are Endo, Actavis, Janssen, and Sandoz, all of whom are veterans in the pain market and have no competing oxycodone-only products.
After Pfizer (NYSE) returned the rights to Remoxy, an investigational extended-release (or ER) oral painkiller, to Pain Therapeutics (NASDAQ) and DURECT (NASDAQ), there is great uncertainty whether a new drug application (or NDA) for this abuse deterrent formulation of oxycodone could get resubmitted to the Food and Drug Administration (FDA) next year, if at all. However, the market is too big (Oxycontin grossed $2.46 billion last year) and the finish line so close for Remoxy to remain ignored for long. The following companies all have experience in marketing abuse deterrent painkillers. None of them have an extended-release pure oxycodone product whose sales could get cannibalized like Pfizer or Purdue Pharma, the maker of Oxycontin, making them potential partners at least in theory.
Mallinckrodt Pharmaceuticals (NYSE)
Abuse-Deterrent: Exalgo ER, Xartemis XR
Mallinckrodt is the world's largest supplier of controlled substance pain medication and is also one of the top 10 U.S. generic pharmaceutical companies, based on prescriptions written in 2013. It sells an osmotic pump oral tablet formulation of hydromorphone, Exalgo, the exterior of which is hard enough to minimize intentional abused through biting, chewing or extraction. Approved by the FDA on March 1, 2010, Exalgo had total U.S. sales of approximately $230 million for the 12 months ending February 28, 2014, according to IMS Health, but its patent expired this year. On Mar. 12, 2014, the FDA approved Xartemis XR, the first extended-release oral combination of oxycodone and acetaminophen, but did not allow abuse-deterrent language; Mallinckrodt is conducting additional studies and will be submitting additional data in the near future. In addition, Mallinckrodt is still obligated to manufacture Remoxy under the old Pfizer contract, so it's the most logical choice among this group of companies to carry out the commercialization as well.
Endo Pharmaceuticals (NASDAQ)
Abuse-Deterrent: Opana ER
Endo transitioned to a reformulated Opana ER CRF in March 2012 that incorporates a polyethylene oxide matrix rendering the tablet highly resistant to crushing without affecting its ER properties and when exposed to water forms a gel which is difficult to draw into a syringe. Post-marketing surveillance data demonstrated a significant 59% reduction in abuse for nasal abuse (snorting) to go with the already low intravenous abuse rates of the original. However, the FDA concluded that the reformulation can be compromised with methods that won't be repeated here, which was one of the factors allowing Impax and Actavis (NYSE) to launch generic versions of the non-crush-resistant formulation on January 2, 2013 and September 12, 2013, respectively, which negatively impacted revenues. Net sales of Opana ER still reached $227.9 million for the year ended December 31, 2013 and accounted for approximately 9% of Endo's 2013 total revenue.
Abuse-Deterrent: Hydromorphone ER
Actavis is the third-largest generic pharmaceutical company in the U.S. On Sept. 12, 2013 it launched oxymorphone extended-release tablets, the generic equivalent to the previously marketed formulation of Opana ER, which Endo voluntarily withdrew from sale in 2012. Then in May 13, 2014, it received approval from the FDA on its Abbreviated NDA for a generic version of Exalgo.
Janssen Pharmaceuticals, of the Johnson & Johnson (NYSE) family
Abuse-Deterrent: Nucynta ER
Janssen is the world's sixth-largest pharmaceuticals company and sells both immediate and ER versions of tapentadol. Like Opana, Nucynta ER (approved in 2011) was developed with abuse deterrent properties such as a polyethelene oxide matrix (physical barrier) which confers resistance to tablet tampering (crushing, chewing or dissolving), but both were approved prior to issuance of the FDA's Draft Guidance document and their labels do not include any mention of abuse deterrence properties or attributes.
Par Pharmaceutical (private)
Sandoz, the generic pharmaceutical division of Novartis (NYSE).
Abuse-Deterrent: generic versions (pulled off market) of OxyContin by Purdue Pharma
Par Pharmaceutical is the fifth largest U.S. generic company as ranked by IMS sales in Q3 2013, while Sandoz is the world's second largest producer of generics. Both companies settled their respective lawsuits with Purdue and agreed that their formerly marketed products infringed on patents relating to OxyContin and both agreed not to make, have made, use offer to sell, sell, or import generic oxycodone products until separate undisclosed dates. However, the settlement doesn't preclude them from marketing a branded oxycodone product like Remoxy.
Question.... didn't Pfizer buy out King Phama? King owns part of Ptie... if so Pfizer still has interest in PTIE via the purchase of King?
So by buying King, Pfizer doesn't need to pay PTIE any $$$ on FDA approval.... your thoughts.
Painkiller Remoxy (Oxycodone) May Still See An NDA Refiling By Mid-2015
Pfizer announced it was returning the Remoxy rights to the initial filers of the NDA, Pain Therapeutics, the shares of which sank 53% on the news.
However, a search on ClinicalTrials.gov reveals that Pfizer has completed all the necessary Phase I bioequivalence trials required to address the FDA's last Complete Response Letter.
That may be enough to attract a new partner for the original abuse deterrant version of oxycodone, which can gain a significant share of a market worth billions.
Remoxy is a strong investigational painkiller (an extended-release oral formulation of oxycodone) for moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Pain Therapeutics were the original developers of Remoxy, under license and using technology from DURECT to design pills that discourage common methods of tampering at a time when abuse deterrence at the manufacturing level was unheard of. PTIE filed the initial new drug application (NDA) for Remoxy in June 2008 with the U.S. Food and Drug Administration (FDA). King Pharmaceuticals, a partner since 2005, assumed full control of the development of Remoxy in March 2009 and filed a resubmission of the NDA in December 2010. Pfizer acquired King Pharmaceuticals and rights to Remoxy in February 2011. After a second Complete Response Letter (or CRL) from the FDA in June 2011 requesting new clinical studies, Pfizer announced last year it received guidance from the FDA on the exact nature of the needed studies would pursue the development of Remoxy and complete the requirements in time for a third submission in mid-2015.
In a reversal of course, Pfizer notified PTIE on October 27 that it was discontinuing its agreement to develop and commercialize Remoxy, returning all the rights to PTIE. It was a big blow to PTIE, which lost out on $250M in clinical and regulatory milestones and 20% royalties after the first $1 billion in net sales in the U.S. That day, PTIE and DURECT lost 53% and 45% of their market value, respectively. Given that the oxycodone market, even just for the non-immediate release formulations, is in the billions, PTIE cannot hope to market Remoxy on its own and will have to shop for another partner. It will be much easier to secure a new partner if PTIE can show a high probability of Remoxy getting approved. The efficacy of Remoxy is not in question, so it comes down to satisfactorily addressing the CRL issue of bioequivalence. According to PTIE CEO Remi Barbier in the October 30 conference call, he had the impression after talking to Pfizer's people that the NDA can and should be filed. About the only way it would make sense to refile is if all the prerequisites were met. Remoxy turns into a viscous substance that can't be snorted nor injected; it could still be chewed (with terrible taste if done so) which necessitated the oral study. In addition to verifying the abuse deterrent claim, Mr. Barbier mentioned four Phase I trials. A search on ClinicalTrials.gov turned up that Pfizer had indeed conducted such trials for a Remoxy-like product (PF-00345439 in Table 1) in the time frame consistent with after the King Pharmaceuticals acquisition. Likewise, Pfizer also finished most of the same for its own in-house abuse-resistant oxycodone creation, ALO-02.
Table 1. FDA-Required Bioequivalence Studies Completed By Pfizer
Not on ClinicalTrials.gov
Abuse potential, oral
Abuse potential, intranasal
Abuse potential, intravenous
PTIE already has experience in transferring Remoxy from the King Pharmaceuticals agreement, and they will receive assistance from DURECT in examining the data. Thus, the bottleneck seems to be on the speed of the transfer of 100,000s of documents, which could take up to the full 6 months by contract if Pfizer wanted. Pharmaceutics is a cutthroat business, but Pfizer won't help its reputation among its myriad partners, current or future, if it were to be punitive to one of its former allies now. According to the Q3 earnings transcript, CEO Barbier concluded that, "If they have an internal competitive product, product in the same space, sits on the same shelf, targets the same customers. With REMOXY they owe a big fat royalty plus milestones. With their internal program they don't. I mean I kind of see it as a portfolio decision tied to relatively straightforward NPV math." No other explanation makes as much sense; it's certainly not due to Remoxy's efficacy, for which the FDA doesn't have a problem. Hopefully it will be just as easy for a new marketing partner to recognize Remoxy's potential to favorably compete in a multi-billion market.
JANET WOODCOCK MAKES THE CASE FOR REMOXY
FDA: New Opioid Has Abuse-Deterrent Properties
The FDA has approved Hysingla ER (hydrocodone bitartrate, Purdue Pharma), an extended release (ER) opioid analgesic, the first and only hydrocodone product with abuse-deterrent properties.
“In clinical studies, Hysingla ER proved to be generally well tolerated and effective in patients suffering from severe, chronic non-cancer pain,” said Joseph Pergolizzi Jr., MD, adjunct assistant professor of medicine at the Johns Hopkins University School of Medicine, Baltimore.
Hysingla ER has properties that are expected to reduce, but not totally prevent, abuse of the drug when chewed, crushed, snorted or injected, according to the FDA, because the tablet is difficult to crush, break or dissolve. It also forms a viscous hydrogel and cannot be easily prepared for injection. The FDA has determined that the physical and chemical properties of the drug are expected to make abuse by these routes difficult.
“Although the science of abuse deterrence is still evolving, the development of opioids that are harder to abuse is helpful in addressing the public health crisis of prescription drug abuse in the United States,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, who added that THE FDA HAS MADE THE PREVENTION OF OPIOID ABUSE A TOP PUBLIC HEALTH PRIORITY.
“The approval of Hysingla ER, with its abuse-deterrent formation technology, is another example of the FDA’s commitment toward increasing the options for physicians to embrace more socially acceptable opioid prescribing,” said Dr. Pergolizzi, who is also founder and chief operating officer for NEMA Research, which designs and creates clinical trials.
Hysingla ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The new medication does not contain acetaminophen, which is a leading cause of acute liver failure in the United States, according to Purdue.
The company expects to launch the new product in the United States in early 2015 in multiple dosage strengths between 20 and 120 mg, to be taken once every 24 hours.
Come on Boring. With Christmas coming up of course the FDA approved their favorite drug manufacturer's new drug. Another billion or so of sales on top of $4b of Oxy. What did you used to say about the FDA banning Purdue. Looks pretty silly now eh! If you've learned nothing over the past decade about the FDA's weak points then it's a jolly poor show. So poor old Remi is maybe what 4 years behind Purdue on his version of a new safer Hydro. Another one to put on the top shelf although to be fair I think he'd already done that. And is Remoxy any better than the new safer Oxy? The FDA will ensure that its got safety warnings even worse than their favorites. What do you want for Christmas?
Fierce Pharma's take on this subject:
FDA approves Purdue's abuse-resistant Hysingla, a hydrocodone pill aimed at knocking off Zohydro
November 20, 2014 | By Emily Wasserman
The FDA has faced a firestorm of criticism since approving Zogenix's superstrength painkiller Zohydro last year, drawing outcry from lawmakers and industry groups concerned with the drug's all-hydrocodone formula with no features to deter addicts from abusing it. Now the FDA has approved Hysingla, a painkiller Purdue Pharma hopes will poach Zohydro's market share and sidestep the furor that has engulfed that drug.
The agency based its approval on a clinical trial of 905 individuals with chronic low back pain and additional data from studies which demonstrated that Hysingla prevented abuse including oral, snorting and injection, the FDA said in a statement. Regulators are also calling for postmarketing studies to further investigate the drug's abuse-deterrent features in certain patient groups.
"We are proud to offer healthcare professionals and chronic pain patients another treatment option," Purdue Pharma CEO Mark Timney said in a statement. "Hysingla ER is the third product in our pain management portfolio to receive an FDA label describing its abuse-deterrent characteristics. These innovations are an important step forward in helping meet patients' needs while also working to deter misuse and abuse."
Like Zohydro, Hysingla contains an extended-release formula of hydrocodone designed for long-term use. But unlike its predecessor, Hysingla is taken every 24 hours rather than every 12 hours like Zohydro.
And while abuse of Hysingla is still possible, the agency is touting the drug's formula as a way to address prescription drug abuse in the U.S., Director of FDA's Center for Drug Evaluation and Research Janet Woodcock said in an FDA blog post. Hysingla and Zohydro contain larger amounts of hydrocodone than other products because they need to be taken less frequently, and the range of strengths for Hysingla is comparable to that of existing extended-release drugs.
Woodcock also noted in her blog post that the FDA does not expect drugs like Hysingla or Zohydro to increase the number of patients treated with opioids and that the agency plans to monitor prescriptions closely. Zohydro chalked up 3,588 outpatient retail prescriptions dispensed in its first 6 months of marketing, representing only 0.02% of the nearly 18 million prescriptions dispensed for all opioid analgesics during the same month, Woodcock said.
"Preventing prescription opioid abuse is a top public health priority for the FDA, and encouraging the development of opioids with abuse-deterrent properties is just one component of a broader approach to reducing abuse and misuse, and will better enable the agency to balance addressing this problem with ensuring that patients have access to appropriate treatments for pain," she said in a statement.
FDA Commissioner Margaret Hamburg--FiercePharma file photo
As soon as the FDA approved Zohydro in October 2013, FDA Commissioner Margaret Hamburg came under attack by law enforcement, politicians and anti-addiction groups, some calling for her resignation. They said the approval was bad policy destined to lead to more prescription drug abuse and deadly overdoses. The governor of Massachusetts tried banning Zohydro there but was rebuffed by a federal judge who said the governor lacked that authority.
Meanwhile, Zogenix is responding to the public outcry with a new, modified version of Zohydro. In October, the company applied for FDA approval for a capsule formulation of the drug designed to make it difficult for addicts to abuse it by snorting or injecting it. Zogenix expects the FDA to decide on the new version of the drug in the first quarter of 2015. Pfizer and Teva are also developing painkillers that could provide some competition to Zogenix and Purdue Pharma's products.
Proof of concept for Remoxy?
From Bloomberg 11/21/14:
Purdue Pharma Wins Approval for Abuse-Deterrent Pain Pill
By Anna Edney and Caroline Chen - Nov 20, 2014
Purdue Pharma LP won approval for an extended-release pure hydrocodone painkiller, the first to hit the market deemed to deter abuse.
The Food and Drug Administration said today it cleared the drug Hysingla ER with a label that indicates the tablet is difficult to abuse via injection or snorting. Closely held Purdue’s Hysingla will compete with the only other approved pure hydrocodone medicine, Zogenix Inc. (ZGNX)’s Zohydro. The drugs are intended to be liver-friendly alternatives to drugs including Vicodin that mix hydrocodone with less-potent medicines such as acetaminophen.
Prescription opioid painkiller abuse was linked to 17,000 deaths in the U.S. in 2011, according to the Substance Abuse and Mental Health Services Administration. The FDA has pushed companies to develop painkillers that are harder to abuse by recreational users. Hysingla, which is formulated to be taken once a day and is targeted at patients who need long-term pain management, is the fourth medicine cleared for sale with abuse-deterrent labeling.
“The FDA continues to strongly encourage development of opioids that deter abuse,” Douglas Throckmorton, the deputy director for regulatory programs, said in a conference call with reporters.
Zohydro isn’t approved with an abuse-deterrent formulation though San Diego-based Zogenix said Oct. 1 it had submitted an application to the FDA for a version of the drug that would make injection or snorting more difficult. The agency is reviewing Zohydro and can withdraw the drug if it is deemed unsafe or ineffective, though the agency hasn’t set a timeline for a decision, Throckmorton said.
The FDA “has not yet determined whether Hysingla ER will prove to be safer than Zohydro ER,” Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, wrote in a blog post today.
The agency approved updated labeling last year for Stamford, Connecticut-based Purdue’s OxyContin that indicates it thwarts abuse and said it won’t allow generic versions on the market without similar properties. The agency also has granted abuse-deterrent labels for Purdue’s Targiniq ER, which combines oxycodone and naloxone, and New York-based Pfizer Inc. (PFE)’s Embeda ER, which combines morphine and naltrexone.
The FDA held a meeting Oct. 30-31 on developing abuse-deterrent opioid medications.
OxyContin and Hysingla contain polyethylene oxide, a gel that absorbs fluid in the gastrointestinal tract and expands to extend the release of the drug. The polymer makes the painkillers tough to crush or dilute with water for injection, David Haddox, vice president of health policy for Purdue, said in an interview.
The drugs’ labels caution that abuse is still possible by injection, snorting and taking orally. Purdue is required to conduct post-marketing studies to look at the impact on abuse, said Sharon Hertz, deputy director of the FDA’s division of anesthesia, analgesia, and addiction products, on the call. It may take “a few years” to see the outcomes, she said.
Purdue has already begun such studies for OxyContin. Since OxyContin’s label was the first approved to reflect abuse-deterrence properties, the company didn’t tout the benefit to doctors while it studied the drug to determine whether the methods reduce abuse. Haddox said preliminary data show it works. The results have given Purdue assurance to begin informing doctors about the advantage, Haddox said.
“There’s a change in this going forward,” he said.