Source: MedScape 3/16/15
Abuse-deterrent formulations (ADFs) of opioid analgesics can have the intended purpose of curtailing abuse, but their effectiveness has "clear limits," a new study confirms.
Theodore J. Cicero, PhD, and Matthew S. Ellis, MPE, from Washington University, in St. Louis, Missouri, found that introduction of ADF oxycodone (OxyContin, Purdue Pharma LP) led to an initial steep decline in abuse of this widely prescribed opioid, but this was followed by a plateau, resulting in "significant" levels of residual abuse.
The investigators also observed an uptick in heroin use after the introduction of ADF OxyContin, as has been observed previously.
"This change is a matter of considerable concern from a public health perspective given the toxicity of heroin in terms of overdose deaths, problems associated with injection and the transmission of infectious disease, crime, and so forth," the authors write.
The study was published online March 11 in JAMA Psychiatry.
Rise in Heroin Use
In 2010, as reported by Medscape Medical News at that time, the US Food and Drug Administration approved reformulated OxyContin to mitigate the risk for overdose. Instead of turning to a powder that can be injected, chewed, or snorted, the new formulation turns into a gummy gel when crushed.
To examine OxyContin abuse patterns and behaviors, Dr Cicero and Ellis surveyed 10,784 men and women in their early 40s who had opioid use disorder and who were entering one of 150 drug treatment programs across the United States. They also interviewed a subset of these individuals.
The investigators report that ADF OxyContin led to a significant decline in past-month abuse after its introduction (from 45% in January–June 2009 to 26.0% in July–December 2012, P
Nice C&P Jimbo - so what do you think or are you so fed up with PTIE that you don't even profer any thoughts of your own these days. Clearly they are being royally screwed by PFE - but you can hardly blame PFE after the way Remi dissed them. I've been told that the junkie resistance of Remoxy is virtually non existent these days. Things have moved on in the last 7 years. The chances of Remoxy ever being approved are about as great as you quitting cross-dressing. Oh the days when you were Debs - or Icha - or Rod - and you used to chat to yourself on this Board. And you a well known Venture Capitalist from .... Those were the days eh!
Cash and investments were $40.6 million at December 31, 2014. In 2015, we expect net cash usage to be approximately $12 million.
"Our current priority is to work cooperatively with Pfizer on an orderly transfer of REMOXY", said Remi Barbier, Chairman, President & CEO. "We are excited by the prospect of regaining worldwide rights to REMOXY. In 2015 we plan to keenly focus on REMOXY, our main asset. A secondary goal for 2015 is to develop FENROCK, our proprietary abuse-deterrent pain patch. We believe we have the dedicated team in place to advance these two novel drug candidates and look forward to reporting potentially significant progress in the coming year."
In October 2014, Pfizer informed us of their intention to return to us full rights to REMOXY. We expect actual termination to become effective no later than six months thereafter, or April 2015, pursuant to the terms of our Collaboration & License Agreements with Pfizer. Upon termination, Pfizer is obligated to transfer to us data, records, materials and other assets related to REMOXY. Pending such termination, and after we receive and review the totality of data generated by Pfizer, we expect to report a target date for the potential re-filing of the REMOXY NDA.
Financial Highlights for 2014
At December 31, 2014, cash and investments were $40.6 million, compared to $49.8 million at December 31, 2013. We have no debt.
Net cash used in 2014 was $9.2 million.
Research and development expenses increased to $7.3 million in 2014 from $4.9 million in 2013, primarily due to increased investment in early stage drug assets. Research and development expenses included non-cash stock-related compensation costs of $1.6 million in 2014 and $1.3 million in 2013.
General and administrative expenses increased to $5.1 million in 2014 from $4.8 million in 2013, primarily due to increased non-cash stock-related compensation costs. General and administrative expenses included non-cash stock-related compensation costs of $2.1 million in 2014 and $1.8 million in 2013.
Our lead drug candidate, REMOXY Extended-Release Capsules CII, is an oral, twice-a-day formulation of oxycodone for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. We developed REMOXY to discourage certain common methods of tampering and misuse. We expect to regain worldwide rights to this drug candidate pending termination of the Collaboration Agreement and License Agreement with Pfizer.
FENROCK is a proprietary abuse-deterrent fentanyl pain patch in pre-IND stages of development. Our goal with FENROCK is to mitigate the abuse, misuse, overdose and death associated with currently marketed fentanyl patches. The active drug ingredient in the FENROCK transdermal pain patch is fentanyl (CII), a highly potent opioid typically used to manage severe cancer pain. We own worldwide rights to this pre-IND drug candidate.
About Abuse-deterrent Hydromorphone
This drug candidate is an oral QD (once-a-day) formulation of hydromorphone, a strong opioid for the management of moderate-to-severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. We are developing abuse-deterrent hydromorphone to discourage certain common methods of tampering and misuse. We own worldwide rights to this Phase I drug candiate.
I wonder what bonuses they paid themselves in 2014. Of course they will be giving themselves a big bonus upon the refiling of Remoxy - should it ever get that far. The next problem will be that the patent expires before FDA approval.
Yes I was wondering the very same thing. Will they revert back to no CCs or continue with their new more open policy?
So we were supposed to have heard more details about the new product in late summer/early fall of 2014 but haven't. This was the product that was even better than Remoxy - well that probably wouldn't be difficult! So we can at least expect news on that as well as an update on where we are with the Remoxy data. Has it been shipped from PFE to PTIE yet? Maybe PFE will run down the clock and to be honest I would expect them to as Remi's relationship with PFE has been poor and he therefore can't expect any favours from them now. Remoxy is now a potential competitive product to PFE and any delays in its progress would be good for PFE. So in 6 months time PTIE will probably get a delivery truck rolling up on their doorstep with a complete jumble of paperwork.
Wondering if Pain Therapeutics will have a conference call this quarter to update us on their progress? The silence over the last couple of months is not been encouraging.
Purdue always had plenty of 'gifts' for physicians, including anatomical charts, models, and office items like pens and letter openers. One can only speculate what 'other' favors were passed around in the many years of their reign. The relationship with the FDA has been lots more love than hate and any "hate" is of fairly recent origin.
But still Purdue gets its new drugs approved by the FDA first time around. What would you put that down to Boring? The love/hate relationship that exists between Purdue and the FDA has no signs of ending eh? Yet here we are holding worthless pieces of paper in Remi's POS. I'm amazed that a senior venture capitalist like yourself Jimbo is still hanging on and grasping at straws. I thought you guys cut and run at the first signs of trouble. Lost your discipline in your old age eh? Send my best to Debbie and Icha.
Laura Ungar, USA TODAY2:57 p.m. EST December 29, 2014
Prescription drug abuse has killed more than 20,000 Americans a year, filled jails and treatment centers and spawned a resurgence in heroin use. And nowhere is the pill problem more prevalent than in Kentucky's Appalachians, where officials trace its roots to the aggressive marketing of one potent drug: OxyContin.
For seven years, they've forged ahead with a civil lawsuit that seeks to make drugmaker Purdue Pharma pay. As early as next year, it could bring the first-ever jury trial pitting Purdue against an addiction-plagued state over the painkiller, which experts say may lead more communities to file suits. Chicago and two California counties already have.
"This is about holding them accountable," says Kentucky Attorney General Jack Conway. "They played a pre-eminent role in the state's drug problem. This started to explode in the mid-1990s, when Purdue Pharma was marketing OxyContin. The resulting opiate epidemic … is a direct result."
The suit alleges that an aggressive and deceptive marketing campaign misled doctors, consumers and the government about OxyContin's addiction risk, ultimately saddling taxpayers with millions of dollars in social, health care and other costs.
Company lawyers in legal documents say more than a billion dollars is at stake and cite the potential for a "ruinous" verdict. As it's typically difficult to find drug companies liable for harm caused by their products, University of Louisville law professor Timothy Hall says Kentucky's lawsuit frames the issue in a new way, taking a page from the fight against Big Tobacco.
"We disagree on the merits of this lawsuit," says a statement from Richard Silbert, associate general counsel for Connecticut-based Purdue. "Courts in Kentucky and elsewhere have dismissed claims against Purdue because the evidence did not establish that our marketing caused the harm they alleged. We believe that the Commonwealth likewise" won't be able to show it.
No one doubts Kentucky has one of the nation's biggest drug problems. A common refrain in Kentucky's hardscrabble hills is that an entire generation has been lost to pain-pill abuse, with overdoses tearing children from parents and parents from children.
Former OxyContin addict Brad Ellis serves beef brisket
Brad Ellis, 37, of Louisa, Ky., says he was first prescribed OxyContin after a back injury while in the Army. By the time he got home in 2001, he was hooked. He went from doctor to doctor in Appalachia seeking pill scripts and paid people to bring him the drugs from pill mills in Florida. He crushed and snorted them for a quick high.
Addiction wrecked his life, leading to a divorce, broken relationships with children and parents, and jail time. He withered to 118 pounds, "a walking skeleton."
"It was almost a constant addiction for 17 years," said Ellis, who has been sober for 23 months. "Pain pills in this area are huge."
'DROVE THIS REGION CRAZY'
With more than its share of poverty, illness and chronic pain, Appalachia's coal country was vulnerable to pain pill abuse when this drug twice as potent as morphine came along.
Shortly after OxyContin's federal approval in 1995, the lawsuit alleges, Purdue employees promoted the long-acting oxycodone medication as less addictive than immediate-release opioids — telling some health care providers that the drug didn't even cause a buzz.
A 2004 report by the then-U.S. General Accounting Office says Purdue encouraged primary-care doctors to prescribe the drug for a wide range of injuries and conditions — not just severe pain with serious illnesses like cancer. The Drug Enforcement Administration complained that the company promoted this sort of prescribing to doctors who weren't well-trained in pain management, while also giving out OxyContin "starter coupons" for patients and promotional items such as fishing hats and plush seal toys, which are now sold online as collector's items.
OxyContin prescriptions for non-cancer pain shot up tenfold between 1997 and 2002.
In a May 2007 settlement of a Virginia criminal case, Purdue and three executives pleaded guilty to federal charges that they intentionally misled doctors, regulators and patients about OxyContin's addiction risk and potential for misuse. Purdue agreed to pay $600 million in fines; the executives, $34.5 million total. A portion went to reimburse states' Medicaid programs.
But Kentucky refused the $500,000 it was offered, filing its own lawsuit in Pike Circuit Court, with Pike County as a co-defendant. Purdue had it moved to federal court, and it resided in New York for years until being returned to Pike County, where Pike, but not the state, settled its claims.
All the while, Kentucky was drowning in a sea of prescription pills. OxyContin became so ubiquitous it was dubbed "hillbilly heroin." Retail distribution of oxycodone skyrocketed elevenfold between 1997 and 2010, and Kentuckians abused opioids and died of overdoses at some of the nation's highest rates.
"OxyContin changed the face of addiction in this region," says Dan Smoot, president of the eastern Kentucky anti-drug organization Operation UNITE. "It made addicts out of people who otherwise weren't. It drove this region crazy."
When the federal government approved an abuse-deterrent formulation of OxyContin in 2010, many addicts turned to other opioids — mostly pills, but also heroin.
"We've lost nearly an entire generation to prescription drug overdose while Big Pharma has reaped huge profits," said U.S. Rep. Harold "Hal" Rogers, a Republican. "I've been trying to hold (Purdue) accountable for years."
PURDUE HOPES TO PREVAIL
Silbert, the Purdue lawyer, agrees that prescription drug abuse is a serious problem and says that's why the company reformulated the drug to make it harder to snort or inject.
Purdue officials remain confident they will prevail — as they did in a 2001 Kentucky lawsuit brought by addicts. In that case, a U.S. District Court judge wrote that they "failed to produce any evidence showing that the defendants' marketing, promotional, or distribution practices have ever caused even one tablet of OxyContin to be inappropriately prescribed or diverted."
Purdue acknowledges the state's suit will be tougher, especially since their request to move it out of Pike County was denied. In a survey, their expert found that seven in 10 people agreed OxyContin has devastated local residents' lives.
The fight has now turned to the issue of "request for admissions," or what the plaintiff asks the defendant to admit — including allegations that Purdue caused OxyContin to be "excessively overprescribed."
Pike County Circuit Court Judge Steven Combs ruled that Purdue missed a deadline to respond to the state's admissions request, effectively meaning the company is considered to have admitted to the whole list — while he ruled the opposite way for co-defendant Abbott Laboratories. Purdue appealed the decision and lost, then appealed again to the state Supreme Court, which hasn't yet ruled.
If the decision isn't overturned, Purdue lawyers say that will limit them in defending themselves on the case's merits. Combs' orders "confront Purdue with the risk of an immense and ruinous judgment," and damages sought "could produce a record-breaking verdict," lawyers wrote in court documents.
Conway says he's preparing for trial but is open to a fair settlement and would like any money to go toward drug education and treatment.Treatment is what saved Ellis, who now works as a cook at Chad's Hope in Manchester, Ky., the faith-based treatment center where he got clean. Ellis blames only himself for his addiction and says only God could free him from its grip.
"God's what pulled me up," he says. "I don't even crave the drug anymore."