Purdue's SVP Of R&D Talks Opioid Abuse, New Pain Treatments

By Rob Wright, Chief Editor, Life Science Leader
Follow Me On Twitter @RfwrightLSL

Alan Dunton, M.D., joined Purdue Pharma as the SVP of R&D back in November 2015. An executive with over 33 years of discovery and development experience, he has been responsible for the approval of more than 20 prescription and OTC products. But now he faces a new challenge. Purdue Pharma is a company whose name has become synonymous with pain management. And though many of the Purdue’s products have provided pain relief for millions of suffering patients, companies developing drugs to better treat pain do so in the face of what many describe as a global opioid abuse and addiction epidemic. Dr. Dunton sat down with Life Science Leader to share his thoughts on what needs to be done to address opioid abuse and addiction, as well as other developments taking place in the field of pain management.

Life Science Leader (LSL): The abuse and addiction to opioids and prescription pain relievers has been labelled a global epidemic with unintentional overdose deaths having quadrupled since 1999. What do you attribute the cause of this ever-rising problem?

As with most problems, it’s multifactorial. One contributor is the dramatic change to how medicine is practiced today. When it comes to sizing up a patient with a pain that needs to be treated, physicians have very little time to evaluate the patient in terms of the risk factors potentially associated with abusing an opioid. For most physicians that still accept insurance, the practice of medicine has shifted from patient care to productivity — getting the patient in and out quickly. Secondarily, I’m not sure how well medical schools and postgraduate programs are actually training docs how to use medications. They teach pharmacology, biochemistry, etc., but when you really get into it, most physicians learn how to prescribe on the job as either a resident or attending physician. Is this the best way for physicians to learn? Perhaps they learn some tricks, but if you think about what all is in an FDA-approved drug label, one has to wonder if that is really helpful to explain a drug’s utility to a prescribing physician. In addition, many medical schools and residency programs have banned pharmaceutical sales representatives from providing information on how to safely and effectively use new medications. Finally, you have state and local legislative bodies that have, all of a sudden, become highly educated and write laws about no more than a three-day opioid prescription. What does that do? It’s just nonsensical.

LSL: Beyond new types of therapeutics, what do you see as being important solutions to help stem the opioid epidemic problem?

When I think about the root causes as I described above, to me it begins with proper and ongoing training and education of physicians. For example, there is very little guidance/knowledge on how to properly taper a patient off of an opioid. I can’t tell you how many phone calls I get from friends who have had an orthopedic procedure and were prescribed an opioid for about a month, but then were stopped (not tapered) by their physician. As a result, these patients experience withdrawal because they have become physically dependent. But just because someone has become dependent doesn’t mean they are addicted. We need a significant amount of educational to not only train clinicians on when to use opioids in the first place, but how to prescribe to patients at both the beginning and end of therapy. We also need to educate insurance companies so that reimbursement matches prescribing behavior.

LSL: Some thought leaders are proposing that future generations need to be prepared for pain self-management. Can you elaborate on what this concept means, as well as some of the pros and cons to such an approach?

Some of these “thought leaders” probably haven’t been in a retail pharmacy lately, because there’s a whole aisle devoted to analgesics. The natural flow (unless you’ve been in a car accident or something) is that when you have a pain you go to your pharmacy. For the most part, unlike in the old days, there is no learned intermediate pharmacist. Depending on what you think you might have, you walk down an aisle and pick from any number of options (i.e., topical creams, patches with mentholatives or lidocaine, acetaminophen, ibuprofen, naproxen, etc.) Self-pain management is not for future generations, it’s here today. Given the structure of the current U.S. healthcare system, a lot of patients either can’t afford to go to go to the doctor, or because of high deductibles, avoid seeking pain treatment from their physician unless it becomes completely unbearable. Patients seeking proper pain management are impacted by the level of pain being experienced, as well as the financial pain seeking care might cause. I would imagine that greater than 50 percent of patients experiencing pain are successfully managed by a trip to the pharmacy.

LSL: Do you see any technologies being developed that could supplant opioids?

Right now I don’t see any game changers. While pain management drug development companies all have the goal of developing an analgesic that has the efficacy of an opioid without all of the negative properties (e.g., addiction, constipation), industry hasn’t yet achieved that goal. We did have a program (as did other companies) looking at biased opioids, meaning the drug is particularly biased to treating pain rather than causing the various side effects. However, nothing has come of this yet. One company, Trevena, recently announced some data regarding the development of Oliceridine (TRV130), a μ-receptor G protein pathway selective (μGPS) modulator it has in development for the management of moderate-to-severe acute pain. And while a worthy goal, the recent announced results demonstrated that it wasn’t a significant improvement over what is currently available, it still produces side effects, and as a result, the company’s stock got slammed. At Purdue we continue trying to develop a molecule (or combination of molecules) that can produce the level of pain relief achieved with opioids without the negative side effects. One of the possibilities looked to be the development of nerve growth factor (NGF) antibodies. But these seem to have a whole series of problems as well (e.g., negative issues on bone and bone formation). From my perspective, I don’t yet see anything on the horizon that is going to replace opioids. As such, we need to focus on proper usage while trying to minimize the negative side effects. This is why Purdue Pharma and Shionogi are working together to launch Symproic, a peripherally-acting mu opioid receptor antagonist (PAMORA) for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain (CNCP).

LSL: What about next generation/future therapeutics for pain management.

We already have implantable devices that can deliver pain relief over an extended duration without giving any drug at all. Transdermal pain delivery systems and patches continue to improve. Pills and tablets continue to get smarter. For example, there are some companies investigating implanting release devices so that if more than one tablet is present in a person’s body it won’t release too much of the drug, which might help to prevent opioid overdose. Advances are being made in the formulation of oral pain medications such that they can have more of a targeted release within a specific area of the GI system. There are implantable drug delivery systems that can help ensure compliance. However, one of the downsides of these (right now) is that if a patient has a problem, you need to have a surgical procedure to have it removed. There are sustained-release injections, which we’ve had for a while, that can improve compliance. One of the things we have been investigating is using the eye as a place of delivery for a pain drug, and not just for ophthalmic indications. The largest organ in the human body is the skin, and so patches, gels, and creams are still of significant interest to take advantage of that drug-delivery platform. This is one of the reasons we continue to think very deeply about topical delivery of drugs. In the future I think we will have ways of altering our genomic signals up and down by making modifications of proteins produced in DNA. Perhaps we will eventual be able to modify how pain is experienced through genomic signal modification.

LSL: What is Purdue working on?

We currently have three Phase 2 programs with novel, nonopioid mechanisms of action for the treatment of pain currently in the clinic. The first is called TrkA (pronounced trek-A). This is a product we licensed in from VM Pharma in late 2015. We also have a product via collaboration with Shionogi called a TRPV1 (pronounced trip-v-one). In addition, we have a something that binds to sigma-1 in the brain and central nervous system under development with our colleagues at Laboratorios Esteve, S.A.U (ESTEVE), an international pharmaceutical company headquartered in Barcelona, Spain. A lot of companies focused on developing novel pain medications are currently investigating three types of sodium channels (i.e., Nav 1.7, 1.8, and 1.9), with the goal being to find a target that only applies to pain. Nav 1.7 is a protein receptor involved in pain signaling. It was first discovered by investigating patients who couldn’t sense pain, which, as it turned out, is the result of a genetic mutation where these patients didn’t have Nav 1.7 receptors. Purdue is collaborating with AnaBios to accelerate Purdue’s Nav 1.7 candidates utilizing AnaBios’ Phase-X discovery platform.

LSL: What about work being done to remove the subjectivity of a patient describing their pain level and coming up with more objective diagnostics?

Because of pain’s subjectivity, work is ongoing to better quantify what it is. Unfortunately, we are kind of are stuck with the 1-10 scale. Then you get into all the nuances of comparing it to the day previous. That’s one of problems in getting a new analgesic to the marketplace is that the scales for evaluating pain are very deficient. But there is work going on more at the NIH to try to better quantify new pain scales.