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Testimony before the U.S. House of Representatives
Statement of Stephen E. Johnson Executive Director, Commercial
Planning Pain Therapeutics, Inc.
Committee on House Government Reform Subcommittee on Criminal Justice,
Drug Policy, and Human Resources
July 26, 2006
Mr. Chairman and Members of the Subcommittee, I am Stephen Johnson,
Executive Director of Commercial Planning at Pain Therapeutics, Inc.
Pain Therapeutics is one of a handful of biopharmaceutical companies
in the United States specializing in the research and development
of safer drugs for use in pain management, particularly opioid analgesics
specially formulated to reduce prescription drug abuse and misuse.
We commend the Subcommittee for holding this hearing, and I am grateful
for this opportunity to discuss what has become an enormous public
health problem. I would like to begin by reviewing the problem of
prescription drug abuse, then turn to a brief and non-technical discussion
of how novel pharmaceutical technology might address this new drug
epidemic. I will then close with four recommendations for your review
and consideration.
As this Subcommittee knows all too well, prescription drug abuse continues
to have a widespread and devastating effect on American families,
businesses, and our society as a whole.
Pain Therapeutics, Inc.
Non-medical use of prescription drugs is the second-most prevalent
category of drug abuse, after marijuana. In fact, 56 percent more
Americans abuse prescription drugs than abuse cocaine, heroin, hallucinogens,
and inhalants - combined.2 Among teenagers, the problem of prescription
drug abuse is even more worrisome. According to recent data published
by the Partnership for a Drug-Free America, 19 percent of children
ages 12 to 17 report having abused prescription drugs, of which the
largest category is pain relievers.
Prescription drug abuse inflicts enormous costs on our society. In
2002 alone, abuse of prescription drugs cost Americans nearly $181
billion. Direct costs related to non-medical use of prescription drugs
are considerable - for example, 25 percent of visits to hospital emergency
departments are associated with abuse of prescription drugs. Indirect
costs result from drug theft, the commission of crimes to support
addiction, "doctor shopping," lost productivity and wages, and the
administration of law enforcement.
The largest group of prescription drug abusers is comprised of individuals
who abuse opioids,6 a class of drugs widely prescribed to treat pain.
Examples of prescription opioid drugs include oxycodone, hydrocodone,
morphine, and fentanyl. When both appropriately prescribed by a physician
and used properly by a patient, opioid drugs can manage pain, especially
severe chronic pain due to cancer, failed back syndrome, or advanced
forms of arthritis. When abused, however, opioid drugs can also induce
some sort of extreme euphoria. Chronic drug abusers will repeatedly
pursue the experience of such euphoria without regard for their well-being
or the welfare of others.
Interestingly, there currently is no way to predict which patients
will end up abusing opioid drugs.
Moreover, just this week, researchers at the Centers for Disease Control
and Prevention published a study revealing that opioids account for
more overdose deaths in the United States than either heroin or cocaine.
For these reasons, and many others, I believe the pharmaceutical industry
must have a leadership role in preventing the abuse and misuse of
opioid drugs.
For abusers, the appeal of a prescription drug typically depends on
its dose strength and the ease with which it can be abused. Illustrative
is OxyContin, a strong, oral opioid drug typically prescribed to treat
moderate to severe pain. Unfortunately, it is also reported to be
one of the most commonly abused, branded, prescription controlled
substances in the United States. The active ingredient in OxyContin
is oxycodone, a potent opioid which is a Schedule II controlled substance
because it has an abuse liability similar to morphine. OxyContin contains
a very high dose of oxycodone that, when used properly, is intended
to be slowly released over 12 hours. Drug abusers, however, can quickly
and simply disable OxyContin's controlled release mechanism - usually
by crushing, breaking, or chewing a tablet, or by stirring it in high-proof
alcohol for a few minutes. The extracted oxycodone is then ingested,
snorted, or injected, immediately releasing into the body a dose of
drug that was intended to be slowly delivered over a 12-hour period.
The ease of abuse, combined with the potency of the active drug ingredient,
allows drug abusers to experience a very powerful and immediate high
According to the Drug Enforcement Administration (DEA), criminal activity
related to OxyContin abuse and diversion is rapidly depleting the
resources of law enforcement.8 In fact, DEA reports record the theft
of 1,369,667 dosage units of OxyContin between January 2000 and June
2003.9 Moreover, fully 25 percent of the Schedule II investigations
conducted by DEA between Fiscal Year (FY) 2001 and FY 2003 involved
OxyContin.
While urgent action is needed to more adequately address this epidemic,
it is also critically important that any efforts to prevent prescription
drug abuse not unduly restrict appropriate access to effective pain
therapies for the patients who need them. In fact, pain already is
too often undertreated. Unfortunately, criminal and civil liability
and theft associated with OxyContin are discouraging some doctors
from prescribing the pain treatments their patients need, and dissuading
some pharmacists from stocking them.
Under the Controlled Substances Act (CSA), DEA is responsible for
maintaining a closed system of distribution for controlled substances
by administering stringent requirements applicable to manufacturers,
distributors, physicians, and pharmacists. Such requirements include
registration, recordkeeping, reporting, security, scheduling, production
quotas, and import/export authorization. Over the years, these controls
have been particularly effective in dramatically reducing diversion
at the manufacturer and distributor level, a significant source of
diversion when the CSA was passed. However, traffickers and abusers
currently divert Schedule II opiates from the retail level (physicians
and pharmacists), where the federal government has less control. Currently,
Federal efforts to address prescription drug abuse principally rely
on costly and sustained risk management approaches, including: physician
and patient education, surveillance of the distribution and dispensing
of controlled substances, marketing restrictions, warning labels,
and law enforcement.
Unfortunately, despite the tireless efforts of thousands of Federal,
State, and local officials working to implement these practices, as
well as the enormous financial resources appropriated to support them,
the incidence of prescription drug abuse has continued to rise - even
as the rate at which other categories of illicit drug use have decreased
or remained stable. In fact, the number of Americans abusing prescription
drugs rose 94 percent between 1992 and 2003, a period during which
the U.S. population increased only 14 percent.14 Moreover, during
the same period, there was a 212 percent increase in the number of
children ages 12 to 17 abusing prescription drugs, and, remarkably,
a 542 percent increase in teens initiating abuse of prescription opioids.
Notably, approximately 600,000 Americans became new abusers of OxyContin
in 2004 alone. Clearly, additional methods of combating prescription
drug abuse are necessary.
At Pain Therapeutics, we believe that the battle against prescription
drug abuse is a shared responsibility among government, the healthcare
community, and the pharmaceutical industry. The use of novel pharmaceutical
technology can help combat the problem of prescription drug abuse.
In fact, our scientists are using innovative chemical advances to
develop a tamper-resistant capsule that provides long-acting, effective
pain relief when used properly, while also resisting degradation under
conditions of abuse.
For example, our investigational drug product Remoxy is a novel form
of long-acting oxycodone. The capsule, which contains oxycodone in
a highly viscous fluid, is formulated to be resistant to tampering
or accidental misuse. While Remoxy is not intended to be abuse-proof
- a sophisticated chemical laboratory might still manage to extract
its active ingredient - it cannot be readily broken, chewed, or crushed,
which are the principal means by which abusers disable the extended
release mechanism of OxyContin and other sustained release opioid
drug products.
Importantly, although the labeling for Remoxy will ultimately be determined
in the course of Food and Drug Administration (FDA) review, we believe
this investigational drug will also reduce the potential for accidental
overdose, which too often occurs when elderly patients and others
who find an OxyContin tablet difficult to swallow ingest its contents
after crushing, breaking, or chewing it. Moreover, we expect Remoxy's
advanced technology to be useful in reformulating other commonly abused
opioid drug products to similarly render them abuse-resistant. Remoxy
is currently in late-stage testing in nearly 40 clinical sites across
the United States. We hope to be able to file for approval to market
this novel formulation in late-2007.
We are taking a very different approach to reducing prescription drug
abuse in developing Oxytrex, an investigational drug product that
combines oxycodone, an opioid agonist, with an ultra-low- dose of
an opioid antagonist. Research has shown that the addition of an ultra-low-dose
opioid antagonist blocks activation of the body's excitatory opioid
receptors, while allowing the agonist to block the transmission of
pain signals.17 We are working to demonstrate that Oxytrex can significantly
inhibit pain while simultaneously reducing the risk of physical dependence,
which is a physiological adaptation to the continued use of a drug
that can often lead to both a diminished physiological sensitivity
to the drug's effects (tolerance) and adverse physical symptoms upon
withdrawal of the drug's use.
We believe that prescription drugs that are specially formulated to
reduce the risk of abuse can significantly contribute to current efforts
to address the nation's prescription drug abuse epidemic. Importantly,
abuse resistant prescription drugs could also diminish the burden
on law enforcement. Additionally, the development of such products
represents a new and efficient means of addressing Congress' increasing
concern regarding prescription drug safety, and could do so without
further restricting or discouraging access for patients who need such
care. In fact, the availability of such products could enhance appropriate
prescribing of opioid drugs by diminishing the stigma associated with
commonly abused drugs and reducing the threat of civil and criminal
liability that can discourage physicians from prescribing more readily
abused prescription controlled drugs.
Pain Therapeutics is not alone in recognizing the potential benefits
of formulating prescription drugs to reduce abuse. In fact, several
governmental entities and organizations have been urging the development
of abuse-resistant prescription drugs. For example, over the past
several years, DEA has repeatedly indicated that it is working closely
with the FDA "to strongly urge the rapid reformulation of OxyContin
by Purdue Pharma, to the extent that is technically possible, in order
to reduce the abuse of the product, particularly by injection." Additionally,
the FY 2006 House Appropriations Committee report notes that "[p]roviders
and patients alike will benefit from the expedited review of safer
drugs, as well as the provision of information that accurately differentiates
abuse-resistant formulations." Meanwhile, the corresponding House-Senate
Conference report advises that "new drug applications and supplements
seeking approval for replacement or alternative abuse-resistant formulations
of currently available drug products that include an active ingredient
that is a listed chemical under the Controlled Substances Act . .
. may be considered under the expedited, priority review process at
FDA."
Further, the 2006 "Synthetic Drug Control Strategy" issued by the
Office of National Drug Control Policy lists as its third of 46 recommendations:
"Continue to support the efforts of firms that manufacture frequently
diverted pharmaceutical products to reformulate their products so
as to reduce diversion and abuse." A comprehensive report issued in
2005 by the National Center on Addiction and Substance Abuse at Columbia
University goes even further, urging:
The FDA should require pharmaceutical companies manufacturing controlled
drugs to formulate or reformulate the drugs where possible to minimize
the risk of abuse.
Pharmaceutical companies should be required to demonstrate in their
application materials for FDA approval of new drugs that they have
made every effort to formulate the drug in such a way that avoids
or at least minimizes the drug's potential for abuse.
Earlier this year, National Institute on Drug Abuse Director Dr. Nora
Volkow coauthored a paper on opioid analgesic abuse calling for development
of "less abusable, but still potent, forms of opioid agents," as well
as "combinations of medications that can be given to treat pain but
to minimize the chances of addiction."
Now we must turn these statements into real public health and law
enforcement achievements. Currently, there are no Schedule II prescription
controlled drugs on the market specifically formulated to resist or
reduce abuse. No trailblazer exists to guide industry in determining
whether and how to pursue development of such products. Moreover no
statute, regulation, or administrative guidance specifically addresses
issues that are critical to determining whether it will continue to
be worthwhile to invest in the research and development to bring such
products to market. This Subcommittee can play a unique role in ensuring
that agencies across the government coordinate their efforts to maximize
the benefits of pharmaceutical technology in addressing drug abuse
and misuse.
We recommend the following:
1. Applications to market prescription drugs that are specially formulated
to deter abuse or misuse should be eligible for priority review.
2. FDA should permit labeling that accurately conveys the specific
means of abuse or misuse to which a product has been shown to be resistant;
and the agency should not require companies to demonstrate resistance
to all potential methods of abuse and misuse, such as those that are
relatively uncommon.
3. Risk management plans for abuse-resistant products should reflect
their inherent safeguards. Appropriate risk management plans could
encourage physicians to prescribe those products that deter abuse
and misuse, while also discouraging use of prescription drugs known
to be readily abusable.
4. We must recognize that achieving approval and meaningful labeling
for these products will be a pyrrhic victory if patients are not given
access to products incorporating abuse- and misuse- resistant technologies.
Given the cost of prescription drug abuse and misuse to our healthcare
system, we must ensure that both private and governmental payors,
such as Medicare Part D plans and the Medicaid program, recognize
the benefits of these products, and favor their use in their formularies.
As a first step, we welcome FDA's recent announcement that it intends
to develop this year guidance for industry on both "Assessment of
Abuse Potential of Drugs" and "Developing Analgesic Products for the
Treatment of Pain," and we are hopeful that the prompt issuance of
these documents will eliminate some of the current ambiguity that
may be discouraging development of prescription drugs formulated for
reduced abuse potential. We hope such guidance will seek to encourage
the development of abuse-resistant prescription drugs by instituting
reasonable standards for accurate labeling that clearly differentiates
products incorporating such technologies from products providing no
abuse- or misuse-deterrent benefit.
Mr. Chairman, we are especially grateful to you and the other Members
of the Subcommittee for calling attention to this issue today. Pain
Therapeutics looks forward to working with Congress, FDA, DEA, and
other government agencies to continue to promote the development of
innovative approaches to more effectively address the epidemic of
prescription drug abuse.
Thank you. I would be pleased to answer any questions. |
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