Jeremy Levin, a top global pharmaceutical and biotech executive, is putting his experience to work by leading efforts of the Biotechnology Innovation Organization (BIO) to help rein in a US opioid crisis that has roots emanating from both the legitimate and illegal drug sectors.
Levin, D.Phil, MB, BChir, is chairman and CEO of Ovid Therapeutics, a New York-based company researching new medicines for rare neurological diseases. BIO tapped him in June 2017 to chair its opioid working group, which includes CEOs from big pharma and start-up biotechs.
The working group’s charge, Levin says, is devising public policy changes to battle the opioid epidemic by fostering scientific innovation to develop non-opioid, non-addictive pain drugs.
“I’m motivated by two specific things.” Levin says. “One, to help the patient, and number two, to bolster health care in our society because I think that makes us a better society.”
The problem, Levin says, has been the health care industry’s reliance on opioids, which although highly effective in treating pain in certain circumstances, are also addictive for some patients. Couple that with the aggressive opportunism of illegal drug traffickers, and the US faces a crisis that Levin says costs the nation’s health care system $1.3 trillion and kills 63,000 people a year.
The challenge in the health care community, Levin explains, is getting the public and private sectors to invest in research and development on a scale that matches the problem, and to couple that with medical education. On the innovation side, although the impact of pain far outweighs that of cancer, Levin says venture funding of new, non-opioid medications is 17 times less than the investment in cancer in the past decade, and there are more than 10 times as many new drugs in development for oncology than pain.
Before joining Ovid, Levin served as president and CEO of Teva Pharmaceutical Industries Ltd.; was on the executive management team of Bristol-Myers Squibb Company, where he created and led the “String of Pearls” strategy that resulted in Bristol leading the immuno-oncology field; and was global head of strategic alliances at Novartis Institutes for Biomedical Research, Inc. He also serves on the Board of Lundbeck, Biocon, and The Biotechnology Innovation Organization.
Levin earned his B.A. in zoology, M.A. in cell biology, and D.Phil in chromatin structure, all from the University of Oxford, and his MB and BChir from the University of Cambridge.
In a recent interview with WuXi AppTec Communications, Levin discussed the origins and extent of the opioid crisis, the role of BIO and its members in finding innovative solutions, and his personal commitment to the effort. WuXi’s interview with Levin is part of an exclusive series spotlighting the inside perspectives of thought leaders on topics shaping the future of new medicines.
WuXi: Who is involved in BIO’s opioid working group?
Jeremy Levin: The opioid working group consists of more than 30 CEOs from companies such as Pfizer, MeiraGTx, Merck, Trevena, Chromocell, Biogen, Allergan, Eli Lilly, Orexigen, Egalet, Shire, Alkermes, Celgene, Abbvie, Vertex Pharmaceuticals, Flexion Therapeutics, Braeburn Pharmaceuticals, Collegium Pharmaceuticals, Hydro Biosciences, Centrexion Therapeutics, Purdue Pharma, Regeneron Pharmaceuticals, Alnylam Pharmaceuticals, Contravir Pharmaceuticals, Pacira Pharmaceuticals, Amygdala Neurosciences, Mallinkrodt Pharmaceuticals, and Horizon Pharma.
A significant number of CEOs are involved, as is BIO president and CEO Jim Greenwood, the BIO leadership and Board, and the BIO staff. At this time (about eight months into the program), we have defined our policy initiatives, and are in the midst of rolling out the concrete ideas and potential plans. The staff at BIO has been extraordinarily active and has been very well received in the working offices of Congress, the FDA and in the National Institutes of Health (NIH). We’re focused on ensuring that we tackle the opioid crisis with innovation, and we’re moving at light speed with realistic, practical, and actionable policies and programs.
WuXi: What key factors have contributed to the opioid epidemic?
Jeremy Levin: The origin of the opioid epidemic is complex and multifactorial, and deadly in its result. The recent expansion of the epidemic initiated several decades ago but opioid addiction has been consistent throughout America’s history, and in many other countries including Russia, China, and Afghanistan. Indeed, it was a cause of enormous dislocation, death and destruction in China in the 19th century, and had an impact which carried through for many decades.
Opium was established, legal and widespread in the US in the 19th century. According to Thor Benson, a journalist who wrote an interesting history of opium in the US, in 1895, the pharmaceutical company Bayer synthesized heroin, and Bayer Heroin was released in 1898. Heroin was actually a brand name Bayer created, not just some street name for the drug. Since many people became addicted to morphine during and after the Civil War, Bayer Heroin was used as a pain reliever that could help people get rid of their morphine addiction. Using heroin for recreational or medicinal uses only became illegal in the US under the Heroin Act of 1924. That opened the door and helped drive the illegal flow of opioid and opioid derivatives into the US – a trade that has expanded and exploded in the US. After World War II, there was a significant flow of opioids coming into the US, and in particular, after the Vietnam War.
Then as we look to the 1980s and 1990s, we had something different happen. The entrance of a number of industrial players. During that period, recognizing the benefit that certain opioid derivatives had in pain relief, a number of companies started to produce pills that provided pain relief and they were very, very successful. The only problem is that patients who weren’t addicts became addicted to those pain pills. The consequences of that addiction were a significant number of patients who became increasingly dependent on what was effectively a drug of addiction.
Now that didn’t apply to all patients, but it applied to many. As companies understood this by late in this past decade, they rapidly started to move to control how opioids could be provided. But by then we had a tremendous number of patients who were desirous of opioids coupled with a medical practice of prescribing opioids. And research was being carried out by both ethical and unethical researchers; most trying to find better drugs to help patients, but some trying to find more potent addictive drugs to sell.
Recognizing that there was a problem, the drug industry began to develop new ways to prevent these addictive drugs from being used inappropriately – for example tamper proof products. But at the same time “bad actors” (illegal drug dealers and cartels) were illegally developing more and more active forms of opioids, and they had a ready market.
In addition, the illegal flow of opioid drugs swelled coming from many sources including from Lebanon, from Afghanistan, and even machinery to manufacture enhanced highly potent addictive opioid pills such as fentanyl from China. In some cases, this was a source of revenue for terrorist organizations such as Hezbollah, and in others, unscrupulous business men abroad and in the US were out to exploit the market in the US and Europe.
As a result, unfortunately, we face the fact that we have not just legitimate companies being part of setting the stage for the crisis, we also have a tremendous supply of illegal forms of base drug. While the sources of this crisis today come from a variety of different parts, in large measure, the opioid crisis is now sustained and growing as the result of illegally supplied drugs.
WuXi: Why has the drug industry been slow in developing effective alternatives to opioid pain medicines?
Jeremy Levin: As we analyze this problem, there are very important points to acknowledge. Opioids are effective in treating some types of pain, and doctors are trained and often used to prescribing them. While there are good studies to show where opioids can and should be substituted, they are not, but when that training occurs, usage drops very dramatically.
So the problem comes from a broad set of different and diverse causes that have impinged on the industry’s historical willingness to invest in the area. On the industry side the causes were no venture capital, no pipeline, and no easy route to the market. There is however a renewed interest in developing pipelines and indeed it’s notable that recently Commissioner Scott Gottlieb and the FDA have taken significant steps to insure the FDA helps bring new medicines to market. Funding is flowing to the NIH and we are starting to see a lot more innovation happening in the area.
The track record for developing new drugs in this area has been relatively poor. If you look at clinical drug development, the ability to get a drug approved in new pain indications, which are non-opioid, is low. It’s about five times less likely than the normal 10% approval rates (for all drugs). So about only two percent of drugs for non-opioid pain relief actually get to the marketplace, which is a very poor record. In fact, there are only two instances of new pain drugs being developed in the past 10 years.
As a result, industry has avoided investing in it; and because of that, you find that private investment in this area has been extremely low.
Venture capital investment in this area has lagged as well. Only 3.6% of all venture funding goes into this area, which is negligible. In other words, venture funding for novel R&D in pain is 17 times less than venture capital in cancer over the past decade. So innovation has lagged.
This is really rather remarkable when set against the scale of the problem. It is estimated that the total number of people who suffer from chronic pain in the US is somewhere between 75 million and 100 million people, which is way more than the number of people suffering from cancer. And the cost for treating pain in the US is somewhere close to $600 billion annually; significantly higher than cancer, Alzheimer’s disease or cardiovascular disease.
Then when you couple that to the fact that there are more than 23 million Americans who are addicted to drugs and alcohol one can appreciate the estimated overall economic impact will include not just the $600 billion to treat chronic pain, but also the economic cost and direct health care costs for abuse, which adds another $700 billion a year. So you’re really talking about $1.3 trillion a year in economic costs related to the problem, not counting the attendant human suffering, and yet you only have 3.6% of venture capital going into it and very little industrial investment. Compounding the problem is the historically limited amount of funding going to investigate the root causes of pain and what causes addiction.
With all these diverse factors coupled with an abundance of cheap illegal opioids, you have a situation where it’s very difficult to change the dynamic if only one part of the system bears the burden. It will take all parts to be effective; industry, academia, venture capital, medical education, regulators and law enforcement.
WuXi: Should there be more incentives for companies to develop non-addictive pain therapies? If so, what would you suggest?
Jeremy Levin: I think it’s not about incentives but rather about the ability to see clear routes to approval coupled with fruitful avenues of research. As an industry BIO’s approach is to refine what we as an innovative industry can do to alleviate those aspects we can best address. We are an industry which is focused on innovation so with that in mind we can best address the problem through changes in legislation and regulations to facilitate innovative approaches to solving the issues we face. These need to be addressed through Congress, the FDA and the NIH. That’s what BIO has now done. The changes are all based on three basic principles.
First principle is that we advance our understanding of the biology of pain and addiction to enable the development of innovative treatments, and at the same time ensure there is appropriate and optimal use of existing therapies. There are circumstances where opioids can be used effectively and there are times where patients will be better suited to have access to novel, non-addictive treatments. There is a series of legislative suggestions – bipartisan in nature – that are directed to that objective and contained within the suggestions we are dialoguing with all the relevant stakeholders.
The second principle of this approach is to address the needs of patients. We must ensure that patients suffering from pain or addiction are able to receive the right treatments at the right time with the right support without stigma. Rather than asking these patients to carry yet another burden, or to potentially try to hide their addiction rather than seek help, we need to prioritize support and access to treatment for these patients. We need to ensure that innovatively we think about how we can help ensure that patients get treatment at the right time. Various legislative approaches can be used to address this and we have made recommendations for such legislation.
The final and third principle is to ensure we stimulate research and development of innovative treatments that effectively treat pain and opioid addiction, and prevent abuse. Within the approach we have adopted are recommendations for legislation that encourage funding at FDA and their regulatory approach towards these drugs.
These three principles underlie the initiatives that we as a working group and now BIO as a whole have rolled out to make an impact on this crisis.
WuXi: Will there still be a place for opioid drugs in treatment of chronic pain or will they be eliminated?
Jeremy Levin: Opioid drugs have been present in the pharmacopeia of humankind for at least 2,000 years. It is highly unlikely that they will be removed. More importantly – speaking as a physician – some opioid drugs play an important part of medical practice. But where they do they need to be prescribed within a highly controlled environment and for highly specific indications; and ensure at the same time when there are alternatives ready, people can use them. So I believe it will be difficult to remove opioid drugs entirely. What is required is a framework of defined medical practice and prescription to ensure they are used in the right way.
WuXi: How will non-opioid drug development evolve over the next five to 10 years?
Jeremy Levin: Non-opioid drug development will need to change. Under the legislation we are proposing, that will happen. Indeed there are signs already that those changes may be afoot. According to data assembled by BIO, today there are only 15 non-opioid drug programs under clinical investigation. And of the 125 drugs that are in the pipeline for pain, fully 95 of them are reformulation programs. So we have a long way to go.
Pain is complex and there are many different pathways involved – which is why improving our basic understanding of pain and addiction is a critical part of our strategy. Once we can begin to stimulate research, development programs will follow.
In the pain drug pipeline for novel targets, there are about 20 that are exclusively in pain; some of those involve mechanisms underlying the effects of cannabinoids, others involve deeper understanding of fatty acids, nitric oxide, chemokines, corticoid receptors, and IL-10 receptors. There are about 26 different mechanisms under investigation and we need to insure that this rich area of research is fully explored. So looking to the future, I am hopeful that we can secure adequate basic research funding and begin to tease out the critical pathways and mechanisms. Indeed, if we wish to solve the crisis while addressing the needs of the millions of patients with chronic pain, we need to ensure that this research is robust and vibrant.
WuXi: What technological advances are needed to move this research forward?
Jeremy Levin: That’s very difficult to say. Right now, the oncology pipeline has roughly 2,700 drug candidates, and that’s more than 10 times the total number in the pain arena. With that level of disparity, I don’t believe we can honestly say that as an industry we’ve explored even a fraction of all the avenues of how best to treat pain.
We need to go back to basics and ask the questions about how we are investing our thinking in novel targets for clinical research and early research. We need to understand the new areas of pain including advances in inflammation, immunology, and nerve conductivity. And as we do so, we have new tools which can be applied beyond basic molecular biology. I anticipate we will need to couple the tools of big data analysis, genomic analysis and clinical records, and thereby insure a deeper understanding of the link between addiction, physiology and pain will emerge.
WuXi: Are you planning to get Ovid Therapeutics into this space?
Jeremy Levin: We have no immediate plans to do that and that’s why I was asked to chair the BIO working group; my only interest here is trying to tackle the crisis that we face.
Ovid’s focus is another completely unmet medical need, which is an important subset of the 30 million American families who have a family member who suffers from over 7,000 rare disorders. Our focus is on about 1 million families who suffer from about 100 rare brain diseases. Fortunately, for those 1 million families – unlike in pain research – there has been an explosion over the past five years of deep interest in these areas and as a consequence the area of these rare neurological disorders is showing real promise and an increasingly vibrant pipeline.
Because of this huge increase in knowledge, I’m very optimistic about the work being done and the ability to drive new medicines in the area of rare neurological disorders
WuXi: What motivated you to take on the opioid challenge?
Jeremy Levin: I want to help patients and contribute to solving a tragic health crisis. I believe that a functioning democracy requires a number of very important stabilizing pillars. In addition to the ability to have a free vote, the ability to speak openly and have an independent judiciary, a democratic nation needs that its population be defended, educated and healthy. These factors are what motivate me as somebody who thinks about his role in society and in my industry.
Because of my role as a CEO in the pharmaceutical industry and my work as a physician, I believe my biggest contributions to democracy will be through the improvement of the health of each individual in our nation. I felt that as a member of our society I could not stand by in the face of an opioid epidemic which every year is taking the lives of 63,000 people, devastating communities and costing us as a nation $1.3 trillion. Our society is being undermined by the epidemic which is growing daily. It would be irresponsible for me not to focus some of my time on this problem and provide what support I could in the best way possible to alleviate that.
And the way I can do this is to bring to the table the experiences I have had not just as a doctor but as an executive who has lead large groups of people on a global scale. I believe that experience can and should be applied to helping solve the opioid epidemic.
Ultimately, I’m motivated by two specific things: one, to help the patient; and number two, to bolster health care in our society, because I think that makes us a better society.