The opioid crisis is front and center, as The National Institute on Drug Abuse is raising alarming data on the skyrocketing increase in opioid-related deaths in the US¹, the White House has launched new initiatives to reduce opioid drug prescriptions², and the increasing number of legal settlements with Mallinckrodt³, and Johnson & Johnson⁴ are creating a need for non-opioid options. However, the development of such will medical products comes with many challenges, and emerging biopharmaceutical companies face an uphill battle to develop pain medical products that are safer and more or equally as effective than opioid medications. In this interview, Dr. Steven Fox, CEO of Akelos, Inc., will discuss the environment of non-opioid drug options, and challenges of developing new non-opioid medical products. 

Alexander Neumeister: Where does the field of pain stand right now, and what's the openness

Dr. Steven Fox

of the field for non-opioid pain relief?

Steven Fox: There are two types of pain: acute and chronic. Patients, especially those who had surgery, undergo a lot of pain after surgery, and many physicians would be giving them opioids for the surgery, when that doesn't necessarily have to be done - they could be using other analgesics instead of prescribing them opioids and potentially introducing them to addiction.

Now, what we're looking to do is to treat chronic neuropathic pain. This type of pain can be demonstrated by people with diabetes who have peripheral pain in the toes and hands, people that have shingles, or people on chemotherapy, for example. Hundreds of millions of people worldwide and an estimated 21 million people in the United States suffer from this type of pain and don’t have the right drug for relief. Physicians and dentists are giving them opioids, so patients are not getting a chance to take drugs that are non-addictive or non-opioid. As a result, we now have the worst healthcare crisis in the history of the United States. Last year, more people died in the opioid crisis than HIV at its height, the Vietnam War, and gun and auto deaths combined.

This has led to two massive problems: The first is that there aren’t good non-opioid drugs available to treat chronic neuropathic pain, and the second is that we are now suffering from this opioid crisis because we don’t have an alternative drug available. 

AN:Are you saying that the problem really comes from the fact that there is no adequate treatment available at this point?

That's right. Opioids don’t actually offer much in terms of treating pain. They work by crossing the blood-brain barrier and the spinal cord, which means they reduce the transmission of pain messages to the brain. But that’s actually not very effective at all, and unfortunately, if you combine the lack of efficacy with the potential to become addicted, you end up with high rates of addiction

AN: So, when you look at your development plan, what makes you believe that this will make a significant change?

SF:Well, we have taken Propofol, which is a safe and effective anesthetic used every day in every hospital, and we've altered it. So we believe it's safe and effective. We've tested a previous pharmacophore on animals and in vitro, and we've seen good results with mechanical and thermal stimulation, so now we've altered it again, so the compounds are in vivo and in vitro, and we think we've got an excellent chance to develop a safe and effective drug.

The key is to not cross the blood-brain barrier so that the drug isn’t addictive. And we have created a platform with a tether and anchor and a pharmacophore in conjunction with our drug to inhibit the HCN1 receptor. So with all of that combined, we're hoping that we can get this new drug developed.

AN: What is your plan for designing an effective protocol for non-opioid pain? How do you plan to incorporate protocol design strategy to generate compelling data to compete with the safety and efficacy of opioid treatments? 

SF: We will follow the guidelines provided by the regulatory agencies for all steps throughout the process. We are aware of the specific challenges related to safety and efficacy specifically in the development of a novel pain treatment. Specifically, patient-centered questionnaires often lack the sensitivity to ascertain certain domains of pain experience and pain processing, which is a factor that can contribute to missing signals of efficacy in clinical trials. Therefore, we will focus on a biomarker strategy from the beginning links together objective biomarkers and subjective assessments of the pain experience. Another critical factor that we will address in the clinical trials is the impact of chronic pain on the quality of life and psychosocial functioning. Improvement of quality of life is one key outcome measure in our development efforts because it provides insight into the real-life experience of pain patients and how an effective and safe treatment has the potential to become a life-changer for patients.

Moe Alsumidaie:Will regulatory agencies embrace a medical product like this? 

SF:I believe they'll embrace it, as it is direly needed, and unfortunately, they are still approving some opioid drugs. So I think that they will pay close attention to a non-opioid treatment, and hopefully support innovation in non-opioid drug development for pain.FDA’s initiatives are also driven by patient and physician needs, which is to have access to a non-addictive option for pain relief. Additionally, some states are cracking down on opioid prescriptions. In New York State, for example, I recently took a new course requirement for opioid addiction in order to get relicensed. New regulations require I search for a patient’s opioid history to ensure access to opioids is limited.  

MA: How will investigators respond to a new potential non-opioid therapy?

SF:I think physician investigators are likely to embrace a new pain relief option that is non-opioid. However, I do anticipate some skepticism, especially with the promise of a safe and effective non-opioid medical product, and the potential for trial failure. As an emerging biopharmaceutical company, we plan to address skepticism by partnering with thought-leaders in the area of pain and generating success stories with people who would have otherwise suffered from addiction, had they been prescribed an opioid. Additionally, the value of having a non-opioid medical product is significant, as not only are we addressing the value of reduced pain, but also the value of reducing potential addiction; I believe payers will pay attention to a novel non-opioid medical product.

Alex Neumeisteris Head of Medical Affairs at CliniBiz and specializes in protocol design, drug safety and clinical trial management. Moe Alsumidaie, MBA, MSF, is a thought leader and expert in the application of business analytics toward clinical trials, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials

References

1. https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates
2. https://www.whitehouse.gov/briefings-statements/president-donald-j-trumps-initiative-stop-opioid-abuse-reduce-drug-supply-demand-2/
3. https://www.washingtonpost.com/health/mallinckrodt-reaches-settlement-with-bellwether-counties-in-mammoth-opioid-lawsuit/2019/09/06/1e8a19f8-d0d9-11e9-b29b-a528dc82154a_story.html?noredirect=on
4. https://www.nytimes.com/2019/08/26/health/oklahoma-opioids-johnson-and-johnson.html