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Drug Wars Come to Corporate America - Purdue Pharma Targets Zogenix



Summary/Abstract

A Pharmaceutical Drug War between Purdue Pharma, and Zogenix over the new Hydrocodone Extended Release, a high dosage variation of the number 1 prescribed drug in America (131m prescriptions) and the number 2 drug reported for prescription pain killer addiction is coming to Wall Street.

Content

Sometimes real life is simply stranger than fiction. One can't, no matter how creative and depraved, dream this stuff up. Americans sit by and watch our Government sanctioned US Corporate predatory pharmaceutical cartels whose Ivy League MBAs personnel sporting tailored garments and toting J. Peterman briefcases hijack and ravage our youth with highly addictive opioid drugs.  The Drug War has crossed the border and now can be found on Wall Street. These are the new breed of drug dealers and unlike their illegal competitors outside US borders, the windfall revenues realized from the prescription drug trade have positioned them as a power player in both Washington and State Capitols influencing  drug and criminal justice policy by financing the campaign war chests of many politicians at state and federal levels.

US Opioid sales revenue was reported in excess of 11 billion in 2011 and they are projected to reach the 15 billion dollar level by 2016. To help put this in perspective I have used data from the US Department of Justice and the RAND Corporation which estimated that in 2012 the street value for all illicit drugs smuggled into the US for all Mexican Cartels combined was 6.6 billion with the Sinaloa Cartel reaping 40-60% or approximately 3 billion which is less than or equal to the sales revenue figures for Purdue Pharma’s Oxycontin for 2010 and 2011.  Americans constitute 4.6% of the world population and yet the US dispenses 80% of the worlds prescription opioids and 99% of the worlds hydrocodone. I use the word dispense rather than consume because there is no way to reliably verify that the substances dispensed were consumed.

Purdue Pharma is a Stamford Connecticut based pharmaceutical cartel responsible for the premeditated generation of an unprecedented opioid epidemic that has claimed thousands of lives and helped to spawn the current heroin epidemic. Recently, n March 2014, they  successfully completed their phase three clinical trials of Hydrocodone Bitartrate Extended Release (ER) and last week they filed a NDA (New Drug Approval) with the FDA. Hydrocodone Bitartrate is the opioid ingredient in Vicodin and Loratab which are currently available as a Schedule II substance. Allegedly, Purdue Pharma's version of Hydrocodone Bitartrate ER, unlike the Zogenix comparable and extremely controversial product Zohydro, employs an abuse deterrent formula that prevents users from snorting or injecting the drug. Zohydro was released to the market without tamper proof technology in March 2014 setting the stage for a prescription opioid abuse revival. Zogenix is licensed as the sole US distributor of Zohydro by Alkermes a pharmaceutical company based in Ireland. Zohydro has been under attack since late 2013 by attorney generals from 28 states and countless addiction advocacy groups due to its extremely high abuse and addiction potential and its lack of abuse deterrent technology. It is speculated that it could be several years before Zogenix will have a abuse deterrent version of Zohydo reay for the market. Although the FDA medical advisory panel voted against its approval by a margin of 11-2, it was ultimately approved by the FDA. One might speculate that if the Purdue Pharma version of Hydrocodone Bitartrate Extended Release (ER) gets a green light on the NDA then the political and societal pressures may result in Zohydro being pulled from the market.

Once again, Purdue Pharma is demonstrating their strategic and tactical prowess in market creation and distribution and is poised to remind the market they are the reigning world champion in the prescription opioid addiction world. Predictably, they have done their homework and studied the socio-demographics of hydrocodone abuse and applied a lesson learned during their former Oxycontin campaign which is that each opioid drug appeals to a different user type.  Purdue Pharma after making tens of billions of dollars on Oxycontin over a twelve year period finally developed a tamper proof technology in 2010 in response to political, public and legal pressure. When Oxycontin was originally released to the market, it was well understood by the addiction professional and opioid user communities that the high dosage (up to 80mg) of oxycodone without the diluents previously found in low dosage oxycodone products (Percodan & Percocet) would have tremendous appeal to the opioid abusing community and attract a new cohort of young, middle class white users into the marketplace. Their unprecedented success (annual revenues 2012-2.4 billion; 2011-2.8 billion; 2010-3.1 billion) was achieved by employing unethical marketing practices including misrepresentation of the abuse and addiction potential to the medical community without consideration for the massive collateral damage as measured by lost lives, addiction rates, health care costs, incarceration rates and broken families. This market strategy appears once again to be in motion.

As abuse deterrent formulations are now in the forefront and revenues for Oxycontin have receded in recent years, it would be strategically appropriate for Purdue Pharma to develop a substance with the same abuse and addictive profile as Oxycontin that targets a group that characteristically prefers an oral route of administration which then renders the abuse deterrent formulation irrelevant.  Hydrocodone ER satisfies this requirement. Hydrocodone already holds the number one position (Vicodin, Loratab) for prescribed opioids on the market with an astronomical 131 million prescriptions in its low dosage form distributed in 2013 and is ranked number 2 for prescription opiod abuse. In a study released in the December 2013 edition of Pain Journal of 3,520 opioid users undergoing addiction treatment in 160 facilities in the US, 75% reported that oxycodone and hydrocodone were the preferred drugs in the opioid category of which 44.7% preferred oxycodone (ingredient in Oxycontin) and 29.4% preferred hydrocodone. The study revealed that 64% of the oxycodone users and 25 % of hydrocodone users reported crushing the pills whereas 20% reported injecting oxycodone as opposed to <5% of the hydrocodone reported intravenous use. Personality, gender and age were amongst the variables examined to measure the preference in choice of drug and route of administration. The research revealed that Oxycontin was the clear favorite for intranasal (snorting) and intravenous use and that young males who were not risk adverse had the highest incidence. Of concern and relevance to the tamper proof Hydrocodone ER was the finding that women and older adults typically avoided street markets and intravenous or intranasal administration and preferred oral administration hydrocodone. Historically the acetaminophen contained in hydrocodone products coupled with the low dosages available in these products has limited the escalation of dosage due to the danger of acetaminophen toxicity. The absence of  diluents and high dosage formulation of this product will make this an extremely attractive opioid drug of abuse to this population.

Assuming the study was well constructed, the sample size was large enough to indicate that the tamper proof Hydrocodone ER will garner significant market share in the opioid addiction community amongst both the older and female populations and should have a restorative impact on a troubled Purdue Pharma's balance sheet which, as reported by The Stamford Advocate in February 2014, had declined resulting in substantial workforce reductions. 

There is an old saying that pioneers get shot. Perhaps Zogenix, failing to heed the lessons previously learned by the Purdue Pharma Oxycontin ER experience, is the pioneer in this skirmish.

For supplementary reading on this topic I have included two articles below.



 

 

 

Purdue Pharma News and Media

Purdue Pharma L.P. Submits NDA for Once-Daily Hydrocodone Bitartrate Extended-Release Tablets Formulated to Incorporate Abuse-Deterrent Properties

Data from Clinical Drug-liking Studies Also to be Presented at APS Today

Stamford, Conn. – April 30, 2014 – Purdue Pharma L.P. announced that it has filed a New Drug Application (NDA) with the U.S. Food & Drug Administration (FDA) seeking authorization to market a once-daily, single-entity hydrocodone bitartrate tablet (HYD). This investigational pain medication was formulated to incorporate abuse-deterrent properties designed to make the product more difficult to manipulate for the purpose of misuse or abuse by various routes of administration (e.g., chewing, snorting and intravenous injection). The formulation has not exhibited alcohol-induced dose dumping in laboratory studies. Data from clinical trials assessing the safety, efficacy, and abuse liability of this investigational medication are also being presented today at the 33rd Annual Scientific Meeting of the American Pain Society (APS) in Tampa, Fla.

“This is another important step in our efforts to develop a portfolio of pain medications with abuse-deterrent technology,” said Mark Timney, President and CEO of Purdue Pharma. “I’m proud of Purdue’s leadership role in this important area of pharmaceutical innovation.”

“Healthcare professionals need an array of therapeutic options in order to individualize the care they provide to their patients with chronic pain,” said Todd Baumgartner, MD, MPH, Vice President of Regulatory Affairs and Chief Medical Officer at Purdue Pharma. “If approved by the FDA, we believe this product will be a valuable therapy for use in treating chronic pain that is also expected to deter misuse and abuse by various routes of administration.”

Study data assessing HYD’s safety and efficacy as well as data from studies of HYD’s abuse potential, conducted in accordance with FDA draft guidance on development of abuse-deterrent formulations, are being presented at the APS meeting, including:

  • “Long-term Safety and Effectiveness of Once-daily, Single-entity, Abuse-deterrent Hydrocodone in Chronic Nonmalignant and Nonneuropathic Pain: Results of a Long-term Open-label Study”

    W. Wen, L. Taber, S. Yu Lynch, E. He, C. Munera, S. Ripa

    This study, with a 52-week maintenance-treatment period involving 922 patients, evaluated the safety and persistence of analgesic effect of HYD in both opioid-naïve and opioid-experienced subjects with moderate to severe chronic nonmalignant and nonneuropathic pain. HYD was generally well tolerated, with the most common treatment-emergent adverse events being those typically associated with the use mu opioid analgesics, and no unanticipated safety concerns were identified. Comprehensive audiologic testing did not reveal any ototoxicity associated with HYD. During maintenance HYD treatment, persistence of analgesia and improvement in function were achieved with stable HYD doses. Short‐acting opioid use was stable at a reduced level from screening baseline during the 52‐week HYD treatment period.

  • “A Single-Center, Randomized, Double-blind Crossover Study to Evaluate the Abuse Potential, Pharmacokinetics and Safety of Intranasally Administered Extended-Release Hydrocodone in Recreational Opioid Users”

    S. Harris, S. Colucci, R. Kapil, A. Cipriano, S. O’Keefe, P. Perrino, P. Geoffroy, T. Hopyan, N. Levy-Cooperman

    The intranasal abuse-deterrent properties of HYD were evaluated in 31 healthy, non-dependent subjects with a history of recreational opioid drug use. Subjects received four intranasal treatments (coarse HYD particles, fine HYD particles, hydrocodone powder, and placebo) in a randomized, double-blind, crossover fashion. The fine HYD particle treatment, produced using an industrial mill, was included to test the limits of the abuse-deterrent technology. A primary endpoint for the study was drug liking, measured up to 36 hours after dosing using a visual analogue scale (VAS). The results showed that tampered HYD (coarse and fine particles) had significantly lower intranasal abuse potential than hydrocodone powder.

    As compared to hydrocodone powder, 68 percent of subjects had a reduction of at least 30 percent in maximum drug liking score following coarse HYD, and 64 percent of subjects had a reduction of at least 50 percent. When fine HYD was compared to hydrocodone powder, 72 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 64 percent of subjects had a reduction of at least 50 percent.

  • “A Single-Center, Randomized, Double-Blind, Crossover Study to Evaluate the Abuse Potential, Pharmacokinetics, and Safety of Oral Intact, Chewed, and Milled Extended-Release Hydrocodone (HYD) Tablets in Recreational Opioid Users”

    S. Harris, S. Colucci, R. Kapil, A. Cipriano, S. O’Keefe, P. Perrino, P. Geoffroy, T. Hopyan, N. Levy-Cooperman

    The oral abuse-deterrent properties of HYD were evaluated in 35 healthy, non-dependent recreational opioid drug users. Subjects received HYD intact, HYD chewed, HYD milled, hydrocodone solution, and placebo in a randomized, double-blind, crossover fashion. The HYD milled treatment, produced using an industrial mill, was included to test the limits of the abuse-deterrent technology. A primary endpoint for the study was drug liking, measured up to 36 hours after dosing using a visual analogue scale (VAS). The results showed that HYD intact and HYD chewed had significantly lower drug liking scores than hydrocodone solution.

    As compared to hydrocodone solution, 83 percent of subjects had a reduction of at least 30 percent in maximum drug liking score following intact HYD, and 74 percent of subjects had a reduction of at least 50 percent. When chewed HYD was compared to hydrocodone solution, 69 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 60 percent of subjects had a reduction of at least 50 percent. When milled HYD was compared to hydrocodone solution, 17 percent of subjects had a reduction of at least 30 percent in maximum drug liking score, and 9 percent of subjects had a reduction of at least 50 percent.

  • In Vitro Assessment of the Effects of Alcohol on the Release Rate of Hydrocodone Bitartrate from a Once-daily, Single-Entity, Hydrocodone Bitartrate Formulation “

    Jennifer Giordano, Hugh Huang, Jenny Kianto

    This in vitro dissolution study evaluated the effects of varying ethanol (EtOH) concentrations in simulated gastric fluid (SGF) (4 % EtOH/96% SGF, 10% EtOH/90% SGF, 20% EtOH/80% SGF, 40% EtOH/60% SGF) on the rate of release of hydrocodone from HYD tablets. The results showed that, as the percentage of alcohol in SGF was increased, the rate of release of hydrocodone from the HYD formulation decreased.

Purdue has also conducted a series of additional laboratory-based in vitro abuse-deterrence studies with this investigational formulation. These data along with the results of the human clinical studies have been submitted to the FDA as part of the New Drug Application.

Hydrocodone products are the most commonly prescribed opioid analgesics in the United States1. They are also the most widely abused (nonmedical use), according to the Substance Abuse and Mental Health Services Administration2. Currently available hydrocodone formulations do not incorporate abuse-deterrent technologies.

About Chronic Pain
Purdue Pharma is a leader in developing treatment options for the management of chronic pain, which is one of the most common reasons for visits to healthcare professionals. Chronic pain conditions affect more than 100 million U.S. adults and cost the American economy as much as $635 billion each year in direct healthcare expenses and lost productivity3.

About Purdue Pharma L.P.
Purdue Pharma L.P. and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on persistent pain. Headquartered in Stamford, CT, Purdue is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue can be found at www.purduepharma.com.

Contact:
James Heins

Senior Director, Public Affairs
office: 203-588-8069
mobile: 203-856-2121

Email: [email protected]

Jennifer Soares
Senior Manager, Corporate Affairs & Communications
office: 203-588-7623
mobile: 203-609-1746
email: [email protected]

 


 

 


 

Purdue Pill May Force Zogenix’s Rival Drug Off Market

By Drew Armstrong Mar 12, 2014

Source: Bloomberg

 

Purdue Pharma LP plans to apply for regulatory approval of a tamper-resistant competitor to Zogenix Inc. (ZGNX)’s powerful pain pill, a move that could get its rival’s drug pulled from the market by U.S. regulators.

Purdue’s experimental drug hydrocodone bitartrate met the goal of reducing chronic low-back pain in a final-stage trial, the closely held company said today in a statement. Purdue’s pill is hard to crush and snort or inject, while Zogenix’s Zohydro ER doesn’t have abuse-deterrent features.

Zohydro’s potential for abuse led two U.S. senators this month to ask the Food and Drug Administration to pull the medicine from the market. The concern that the pill could be crushed and snorted was strong enough that when the drug was approved the U.S. regulator said its time on the market could be limited.

“If and when they, or another manufacturer, are able to create an abuse-deterrent formulation that remains safe and effective for patients, we would certainly give serious consideration to assuring that any non-abuse formulations are removed from the market,” Bob Rappaport, the FDA’s director of pain drugs, said in an Oct. 25 review of Zohydro’s approval.

Purdue plans to ask the FDA for a priority review that would cut two to three months off the 10 months the agency sets as a goal to examine applications, according to the company.

Gary Stiles, head of research and development of Stamford, Connecticut-based Purdue, said the company was pleased with the results. “We firmly believe that the market must move to all abuse-deterrent formulations,” he said. “There’s not a technical reason why we and others can’t do that,” he said in a telephone interview.

Study Results

In Purdue’s study of 588 patients with low back pain, 65 percent saw pain improve by at least 30 percent, and 48 percent of patients had improvement of 50 percent, the company said in a statement. The most common side effects included constipation, nausea, vomiting and headaches, which are similar to side effects for other hydrocodone medicines. It hasn’t released full results.

In Zogenix’s clinical trial of Zohydro, 68 percent of patients taking the pill had low back pain reduced by at least 30 percent. Approved as the first painkiller made of pure hydrocodone, the drug started being distributed through select pharmacies at the beginning of March, the San Diego-based company said.

Zogenix Response

Zogenix said it should only be used by patients who can’t take other opioid-based painkillers. Use of the drug is strictly controlled, Zogenix said on its website.

While the drugmaker is working on its own tamper-resistant form of Zohydro, the company said in an e-mailed statement it wouldn’t be available until the end of 2016.

“Zogenix is fully engaged in providing abuse deterrence initiatives, including developing an abuse deterrent formulation of Zohydro ER,” the company said.

The shares of Zogenix have doubled since the drug was approved. Zogenix gained 12 percent to $4.54 in New York yesterday.

U.S. deaths from drug abuse have tripled since 1990, according to a 2013 report from the Centers for Disease Control and Prevention in Atlanta. There were 36,000 deaths in 2008, mostly from prescription drugs, and three out of four of those prescription overdose deaths were from painkillers.

Most Prescribed

Hydrocodone-based painkillers are the most-prescribed pharmacy drugs in the U.S. About 131 million hydrocodone products were dispensed in 2011, according to a January 2013 FDA report.

In letters to Health and Human Services Secretary Kathleen Sebelius, Democratic Senators Charles Schumer of New York and Joe Manchin of West Virginia have said Zohydro shouldn’t be available. “The FDA’s approval of Zohydro ER, in its current form, must be stopped before this dangerous drug is sold to the public,” Manchin said on March 10.

The FDA is tightening prescribing restrictions on pain drugs. In October, the agency said it would make rules re-classifying vicodin and other hydrocodone-based painkillers as schedule II substances, the second-most restrictive of a five-step scale that limits access based on addiction potential. The rules would restrict patients to a 90-day supply, compared to allowing five refills within six months. Zohydro is already classified as a schedule II drug.

Sometimes real life is simply stranger than fiction. One can't, no matter how creative and depraved, dream this stuff up. Americans sit by and watch our Government sanctioned US Corporate predatory pharmaceutical cartels whose Ivy League MBAs personnel sporting tailored garments and toting J. Peterman briefcases hijack and ravage our youth with highly addictive opioid drugs.  The Drug War has crossed the border and now can be found on Wall Street. These are the new breed of dealers and unlike their illegal competitors outside US borders, the windfall revenues heavily influence policy by financing the campaign war chests of many politicians at a state and federal level. US Opioid sales revenue was reported in excess of 11 billion in 2011 and they are projected to reach the 15 billion dollar level by 2016. To help put this in perspective, the RAND Corporation estimated that in 2012 for illicit drugs smuggled into the US for all Mexican Cartels combined was 6.6 billion with the Sinaloa Cartel reaping 40-60% or approximately 3 billion which is less than or equal to the sales revenue figures for Purdue Pharma’s Oxycontin for 2010 and 2011.  Americans constitute 4.6% of the world population and consume 80% of the worlds prescription opioids and 99% of the worlds hydrocodone.

Purdue Pharma, the Stamford Connecticut based pharmaceutical cartel responsible for the premeditated generation of an unprecedented opioid epidemic that has claimed thousands of lives and helped to spawn the current heroin epidemic, successfully completed its phase three clinical trials of Hydrocodone Bitartrate Extended Release (ER) in March 2014 and filed its NDA (New Drug Approval) with the FDA last week. Hydrocodone Bitartrate is the opioid ingredient in Vicodin and Loratab which are currently available as a schedule II substance. Allegedly, Purdue Pharma's version of Hydrocodone Bitartrate ER, unlike the Zogenix comparable and extremely controversial product Zohydro, employs an abuse deterrent formula that prevents users from snorting or injecting the drug. Zohydro was released to the market without tamper proof technology in March 2014 setting the stage for a prescription opioid abuse revival. Zogenix is licensed as the sole US distributor of Zohydro by Alkermes a pharmaceutical company based in Ireland. Zohydro has been under attack since late 2013 by attorney generals from 28 states and countless addiction advocacy groups due to its extremely high abuse and addiction potential and its lack of abuse deterrent technology. Although the FDA medical advisory panel voted against its approval by a margin of 11-2, it was ultimately approved by the FDA.

Once again, Purdue Pharma is demonstrating their strategic and tactical prowess in market creation and distribution and is poised to remind the market they are the reigning world champion in the prescription opioid addiction world. Predictably, they have done their homework and studied the socio-demographics of hydrocodone abuse and applied a lesson learned during their former Oxycontin campaign that being that each opioid drug appeals to a different user type.  Purdue Pharma after making tens of billions of dollars on Oxycontin over a twelve year period finally developed a tamper proof technology in 2010 in response to political, public and legal pressure. When Oxycontin was originally released to the market, it was well understood by the addiction professional and user communities that the high dosage (up to 80mg) of oxycodone without the diluents previously found in low dosage oxycodone products (Percodan & Percocet) would have tremendous appeal to the opioid abusing community and attract a new cohort of young, middle class white users into the marketplace. Their unprecedented success (annual revenues 2012-2.4 billion; 2011-2.8 billion; 2010-3.1 billion) was achieved by employing unethical marketing practices including misrepresentation of the abuse and addiction potential to the medical community without consideration for the massive collateral damage as measured by lost lives, addiction rates, health care costs, incarceration rates and broken families. This market strategy appears once again to be in motion.

As abuse deterrent formulations are now in the forefront and revenues for Oxycontin have receded in recent years, it would be strategically appropriate for Purdue Pharma to develop a substance with the same abuse and addictive profile as Oxycontin that targets a group that characteristically prefers an oral route of administration. Hydrocodone ER matches this requirement as hydrocodone already holds the number one position (Vicodin, Loratab) for prescribed opioids on the market with an astronomical 131 million prescriptions in its low dosage form distributed in 2013. In a study released in the December 2013 edition of Pain Journal of 3,520 undergoing addiction treatment in 160 facilities in the US, 75% reported that oxycodone and hydrocodone were the preferred drugs in the opioid category of which 44.7% preferred oxycodone (ingredient in Oxycontin) and 29.4% preferred hydrocodone. The study revealed that 64% of the oxycodone users and 25 % of hydrocodone users reported crushing the pills whereas 20% reported injecting oxycodone as opposed to <5% of the hydrocodone reported intravenous use. Personality, gender and age were amongst the variables examined to measure the preference in choice of drug and route of administration. The research revealed that Oxycontin was the clear favorite for intranasal (snorting) and intravenous use and that young males who were not risk adverse had the highest incidence. Of concern and relevance to the tamper proof Hydrocodone ER was the finding that women and older adults who preferred avoiding street markets and intravenous or intranasal administration preferred oral administration hydrocodone. Historically the acetaminophen contained in hydrocodone products coupled with the low dosages available in these products has limited the escalation of dosage due to the danger of acetaminophen toxicity. The absence of  diluents and high dosage formulation of this product will make this an extremely attractive opioid drug of abuse to this population.

Assuming the study was well constructed, the sample size was large enough to indicate that the tamper proof Hydrocodone ER will garner significant market share in the opioid addiction community amongst both the older and female populations and should have a restorative impact on a troubled Purdue Pharma's balance sheet which, as reported by The Stamford Advocate in February 2014, had declined resulting in workforce reductions.  For supplementary reading on this topic I have included two articles below.

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