Support for Ohio House Bill 248

Chairwoman Gonzales, Vice Chair Huffman,Ranking Member Antonio and members of the Committee, thank you for the opportunity to testify in support of House Bill 248. My name is Tom Brownlie. I am a Director of US Policy with Pfizer’s Global Policy team, and I am here today on behalf of Pfizer in full support of this legislation.

Pfizer is a research-based global pharmaceutical company dedicated to the discovery and development of innovative medicines and treatments that improve the quality of life for people around the world. We have a broad portfolio of pain medicines, which includes over-the-counter pain relievers, non-opioid prescription medicines, and an abuse-deterrent opioid. We are also investing in the research and development of an additional abuse-deterrent opioid and other non-opioid therapies, including a novel monoclonal antibody therapy that selectively targets nerve growth factor (NGF), a regulator of pain processing and sensitivity that increases as a result of injury or inflammation and in chronic pain states.

I won’t review all of the statistics on opioid abuse. Everyone here understands the gravity of the issue, and I believe others here can speak more personallyto its devastating effects on families, friends, and neighbors. Instead, I will addressissues pertaining to the policy question you are being asked to consider: Should abuse-deterrent opioidsthat the FDA has determined are likely to deter or reduce abuse be part of the solution here in Ohio?

Pfizer believes these technologies can play an important role and should be part of a comprehensive approach to tackling opioid abuse.When incorporated into existing opioids, they have been shown to reducetheir misuse and abuse, and lower prices drug dealers can command on the street, while still achieving their primary objective of providing pain relief to patients. Economic analyses also suggest potential cost-savings due to lower health care costs from fewer ambulance trips, emergency room visits, hospital stays, substance abuse treatment services, and outpatient visits.

To help you understand our position and formulate your own, I will address the following three areas:

  1. What are abuse-deterrent opioids?
  2. What is the evidence they reduce abuse?
  3. How can abuse-deterrent opioids reduce cost?
  1. What are Abuse-Deterrent Opioids?

Abuse-deterrent opioids contain the same pain relieving ingredient as opioids currently on the market; however, they also contain technologies designed to deter unintentional misuse such as chewing and intentional misuse or abuse by drug abusers seeking the “high.” Abuse deterrent opioids provide the needed pain relief to patients, but deter those who are chewing and swallowing, or crushing the pills to snort or smoke, or dissolve and inject.

The FDA has recognized that the development of opioids containing abuse-deterrent properties is an important step towards the goal of creating safer opioid analgesics[i]. In fact, FDA deputy director for regulatory programs, Douglas Throckmorton, M.D., stated that the, “development of abuse-deterrent opioid analgesics is a public health priority for the FDA."[ii]And the Office of National Drug Control Policy included expediting the “development of abuse-deterrent formulations (ADFs)” in its action steps for responding to the prescription drug epidemic.[iii]

In 2013, the FDA took an important step forward by releasing draft guidance to industry on evaluation and labeling, and shortly afterward approved the first drug with labeling stating the deterrent technology is likely to reduce or deter abuse. Earlier this year, the FDA finalized the guidance.[iv]

The FDA defines abuse-deterrent properties as those properties shown to meaningfully deter abuse, even if they do not fully prevent abuse. They further note that they will allow labeling regarding abuse-deterrent properties and associated claims if:

  1. The product has attributes intended to discourage its abuse that have undergone studies in one or more FDA-specified categories, AND
  2. The results of those studies meet or exceed the current FDA performance criteria and, therefore, are expected to result in or have demonstrated a meaningful reduction in abuse.

The FDA also provided a framework for categorizing abuse-deterrent formulation, which includes seven groups(Table 1).i Opioids currently approved by the FDA as likely to reduce or deter abuse incorporate two types formulations: Physical/chemical barrier and agonist/antagonist formulations.

Formulations with physical barriers can prevent chewing, crushing, cutting, grating, or grinding of the dosage form. Formulations with chemical barriers, such as gelling agents, can resist extraction of the opioid using common solvents like water, simulated biological media, alcohol, or other organic solvents. Physical and chemical barriers can limit drug release following mechanical manipulation, or change the physical form of a drug, rendering it less amenable to abuse.

Agonist/antagonist formulations incorporate an opioid antagonist that interferes with, reduces, or defeats the euphoria associated with abuse. The antagonist can be sequestered and released only upon manipulation of the product. For example, a drug product can be formulated such that the substance that acts as an antagonist is not clinically active when the product is swallowed, but becomes active if the product is crushed and injected or snorted.

Table 1: Abuse-Deterrence Categories from FDA Guidance[v]

Category / FDA Description
Physical/ chemical barriers / Physical barriers can prevent chewing, crushing, cutting, grating, or grinding of the dosage form. Chemical barriers, such as gelling agents, can resist extraction of the opioid using common solvents like water, simulated biological media, alcohol, or other organic solvents. Physical and chemical barriers can limit drug release following mechanical manipulation, or change the physical form of a drug, rendering it less amenable to abuse.
Agonist/antagonist combinations / An opioid antagonist can be added to interfere with, reduce, or defeat the euphoria associated with abuse. The antagonist can be sequestered and released only upon manipulation of the product. For example, a drug product can be formulated such that the substance that acts as an antagonist is not clinically active when the product is swallowed, but becomes active if the product is crushed and injected or snorted.
Aversion / Substances can be added to the product to produce an unpleasant effect if the dosage form is manipulated or is used at a higher dosage than directed. For example, the formulation can include a substance irritating to the nasal mucosa if ground and snorted.
Delivery System (including use of depot injectable formulations and implants) / Certain drug release designs or the method of drug delivery can offer resistance to abuse. For example, sustained-release depot injectable formulation or a subcutaneous implant may be difficult to manipulate.
New molecular entities and prodrugs / The properties of a new molecular entity (NME) or prodrug could include the need for enzymatic activation, different receptor binding profiles, slower penetration into the central nervous system, or other novel effects. Prodrugs with abuse-deterrent properties could provide a chemical barrier to the in vitro conversion to the parent opioid, which may deter the abuse of the parent opioid. New molecular entities and prodrugs are subject to evaluation of abuse potential for purposes of the Controlled Substances Act (CSA).
Combination / Two or more of the above methods could be combined to deter abuse.
Novel Approaches / This category encompasses novel approaches or technologies that are not captured in the previous categories.

An objection you are likely to hear is that these technologies are too new to be proven. However, abuse-deterrent technologies are not new. In fact, they have been in development for over 30 years. The firstdrug with abuse-deterrent properties was introduced in 1983 with Talwin NX in response to an increase in abuse, diversion, overdose and death. Since then, companies have continued to develop and improve deterrent technologies. The only thing that is new isregulatory guidance from the FDA defining the evaluation process required for companies to obtain labeling claims regarding the impact of these technologies.

The guidance was a critical step forward that allows, for the first time, doctors, patients, and insurers to differentiate between opioids that simply contain a deterrent technology and those the FDA has determined are likely to deter or reduce abuse. This differentiation is critical and we believe should be foundational to any policy related to abuse-deterrent opioids.

  1. What is Evidence They Reduce Abuse?

What is most critical is the impact these technologies have on misuse and abuse. What benefit do they confer to individuals, families, and communities? Some of the best, real-world data emerged after the introduction of a reformulated version of OxyContin® with abuse-deterrent properties. The reformulated version was introduced into the market in 2010. And at the same time, the non-abuse-deterrent version was removed from the market. This created a “natural experiment” that allowedresearchers to assess misuse and abuse rates, as well as changes in health care expenditures, related to a single drug before and after it was abuse-deterrent.

The findings from these studies are compelling. The researchers found that abuse rates of OxyContin™ decreasedsignificantly across a range of patient types and insurers, including:

  • 49% decrease in abuse among a subset of opioid abusers (23.69% to 12.12%, p<0.0001);
  • 41% decrease in abuse among all individuals (4.06% to 2.41%, p<0.0001);
  • 22% decrease in abuse among commercially insured (3.6% to 2.8%; p<0.001);and
  • 18% decrease in abuse among Medicaid patients (6.2% to 5.1%, p=0.034).[vi]

These were not isolated findings. After introduction of the abuse-deterrent OxyContin™,calls to poison centers involving abuse, therapeutic errors affecting patients, and accidental exposures associated with the drug decreased by 36%[vii]; street value decreased[viii]; and there was a 50% drop in demand for OxyContin™ during pharmacy robberies documented in a nationwide database.[ix]Collectively, these findings provide strong evidence that the abuse-deterrent technology did, in fact, deter and reduce abuse in real-world settings.

Let me address two other objections you will likely hear: Abuse-deterrent opioids “don’t work”and they are not a viable solution because they don’t deter the most common form of abuse, swallowing too many pills. We believe the real-world data, the study data provided to the FDA, and the fact that the FDA has approved labeling claims stating that they are likely to reduce or deter abuse, debunk theargument that they don’t work.

With respect to second objection, indeed, abuse-deterrent technologies cannot prevent abuse by taking too many pills. Instead, they deter the most dangerous routes of administration – smoking, snorting and injecting – which are associated with elevated risk of morbidity and mortality.[x]No solution is perfect and we recognize that abuse-deterrent opioids are not a panacea. Prescription drug monitoring programs and substance abuse treatment services cannot eliminate abuse either, but we understand the value of these solutions and are using them to the extent possible. The same approach should apply to abuse-deterrent opioids.

  1. How Can They Reduce Cost?

The other common question regarding abuse-deterrent opioids as a partial solution to the opioid abuse crisis is, “How much do they cost?”Given that health care costs and insurance premiums have been steadily increasing, this is a valid and important question. Contrary to what others may suggest, this is not a simple calculation solely based on the price of an abuse-deterrent opioid versus a generic opioid without such technologies. To accurately answer the question, an evaluation must, at a minimum, account forcost/price of the medicines, the scope of prescriptions likely to be affected, current expenditures on opioid abuse, and the cost-savings of deterring or reducing abuse.

Price?

Let me start by answering the first question often posed: What is the price of an abuse-deterrent opioid? A starting dose for a patient without insurance paying cash is approximately $7 per dayfor an abuse-deterrent opioid compared to $1 per day for a generic extended release opioid without abuse-deterrent properties.[xi]If the dose is increased by the prescriber three times, the prices wouldgo up to approximately $16 per day and $3 per day, respectively.

Note that patientswith private insurance or Medicaid would pay a co-pay rather than these prices. Furthermore, they do not reflect any discounts or rebates private insurers might negotiate. And they do not reflect what the Ohio Medicaid program would pay since federal law requires, at minimum, a 23.1% rebate and the state shares the cost of coverage with the federal government.

Additionally, these prices reflect the market today, which has three competitors. The FDA approved another abuse-deterrent opioid last month, which is expected to enter the market in early 2016.[xii]And there are multiple innovative biopharmaceutical companies and generic manufacturers developing such drugs, with approximately 30 abuse-deterrent opioids in various stages of development by innovator and generic manufacturers. The FDA has also stated they will release draft guidance for generic manufacturers soon. All of these factorswill increase the market competition, putting more pressure on pricing and negotiations.

Assessing the Correct Scope of Impact

It is important to put the size of the abuse-deterrent market in context. It is assumed or implied by those in opposition to abuse-deterrent opioids that legislation like HB 248 will transform the entire opioid market. That is not true. Opioids are available in immediate- or extended-release formulations, which are used different clinically and prescribed at different rates. The majority of opioids prescribed in the United States are immediate-release, accounting for approximately 90% of all opioid prescriptions.[xiii]Abuse-deterrent opioids are in the extended-release category, where tampering is more common, and account for only 10% of opioid prescriptions.[xiv]Therefore, any fiscal analyses mustaccount for replacement of drugs only in the extended-releasesegment.

Cost of Opioid Abuse Currently in Our Premiums

Direct medical costs of opioid abuse are estimated to contribute $72.5 billion in annual cost to health insurers.[xv]These costs come from more frequent and more intensive use of medical services, and are currently factored into premiums by insurers. For reference, the costs of opioid-related medical services are estimated at:

  • $13,398 for each opioid abuse related hospitalization;
  • $5,745 for each substance abuse treatment service;
  • $5,400 for each complication associated with injection drug-use, such as hepatitis and HIV;
  • $1,175 for each opioid substance abuse treatment service;
  • $1,160 for each emergency department visit; and
  • $727 for each outpatient visit.[xvi]

There are also indirect costs due to loss of productivity and increased criminal activity. Criminal justice cost was estimated to be $5.1 billion annually, which are born by a range of individuals, groups, and institutions, including states[xvii]:

  • Correctional facilities accounted for the largest share with $2.3 billion; nearly two-thirds of these costs were incurred at the state level;
  • Police protection contributed $1.5 billion;
  • Legal and adjudication costs accounted for $726 million; and
  • Property lost due to crime accounted for $625 million.

Impact of Abuse-Deterrent Opioids on Cost

Researchers tracking the impact of the re-introduction of OxyContin® as an abuse-deterrent version found that health care costs decreased by $9,456 and $11,501 per patient for diagnosed abusers insured by commercial carriers and Medicaid, respectively, and health care costs decreased by $7,565 and$6,856 per patient for undiagnosed abusers insured by commercial carriers and by Medicaid, respectively.[xviii] Overall, the introduction of the reformulated abuse-deterrent extended-release (ER) oxycodone is estimated to have saved $430 million in annual health care costs.[xix]

Another economic analysis of the impact of shifting to abuse-deterrent opioids estimated that, afteraccounting for differences in drug cost and health care savings due to reduce opioid abuse, the net health care savings would range between $1,757 per patient and $4,033 per patient, depending upon price and insurance coverage assumptions.

These findings highlight the need to assess cost and savings of abuse-deterrent opioids holistically, rather than focusing on one part of the equation. It also suggests that the only way to assess the validity of arguments in opposition to these innovations is to have answers to the following questions:

What is the average health care cost of an opioid abuser enrolled in your plan?

How much do you spend annually and per patient on each medical service?

What would be the savings of reducing abuse by 10%? … 20%? … 50%?

Like other policy solutions Ohio is investing in to tackle the opioid abuse crisis, such as the PDMP, we believe abuse-deterrent opioids may confer the dual benefit of reducing abuse, which is what our family and friends care most about, and saving the state money, which is your fiduciary responsibility to constituents.

Conclusions

Pfizer recognizes that solving the opioid crisis is extremely difficult and that there is no magic bullet. Abuse-deterrent opioids will not be the sole solution, but we believe they can play an important role as part of a comprehensive approach that addresses misuse and abuse from prevention to treatment to overdose rescue.

Ohioans are currently paying for opioid abuse, personally and financially. The state is also paying for opioid abuse through higher medical costs, criminal costs, and losses in productivity. Maintaining the status quo means we all continue to pay these costs.

We believe this bill is a positive step forward for tackling the opioid abuse issue in Ohio, and encourage you to vote to pass HB 248. Thank you again for the opportunity to speak today. I’d be happy to answer any questions.