In a statement last August, departing FDA Commissioner Scott Gottlieb outlined several steps the agency had planned to further address the opioid crisis. Part of that approach, he wrote, includes supporting development of non-opioid, non-addictive alternatives for acute and chronic pain. The FDA plans to outline a path for developing extended-release local anesthetics, which can serve as an alternative to fast-acting oral opioids. FDA also plans to issue guidance to assist drug sponsors with developing new non-opioid medications for chronic pain. In line with FDA’s plans, research groups, pharmaceutical and biotech companies, and medical device manufacturers have increased efforts to develop non-opioid treatments for acute and chronic pain. To date, we see a few promising developments:
- In October 2018, Heron Therapeutics submitted a New Drug Application to the FDA for HTX-011, an investigational, long-acting, extended-release formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the management of post-operative pain.
- In June, FDA awarded HTX-011 Breakthrough Therapy and Fast Track Designations for post-op pain management. Clinical studies, including two Phase 3 studies, showed HTX-011 demonstrated superior, sustained post-op pain relief for 72 hours, decreased the need for opioids, and resulted in more patients opioid-free when compared to the current standard of care.
- In September 2018, FDA awarded Concentric Analgesics’s pipeline drug CA-008 Breakthrough Therapy Designation. The drug rapidly converts to capsaicin, a strong TRPV1-agonist. Concentric designed the drug to treat pain and eliminate the need for post-op opioids. Results from its Phase 2 clinical trial, conducted in patients undergoing bunionectomy, achieved statistically significant and clinically meaningful reductions in area under-the-curve (AUC) for pain intensity from 0 to 96 hours (33%, p=0.005), as well as from 0 to 168 hours (32%, p<0.05, at rest), compared to the control group. The drug also reduced opioid consumption by 50% from 0 to 96 hours, and 26% were opioid-free compared to 5% in the control group.
- Tremeau Pharmaceuticals is developing TRM-201 (rofecoxib) as a fast-track treatment for Hemophilic Arthropathy, a rare disease typically treated with opioids. The drug received Orphan Designation in November 2017.
- In May 2018, the FDA launched an “Innovation Challenge” to encourage medical device development, including digital health technologies and diagnostics, designed to treat pain and prevent addiction. Evaluating more than 250 applications, the FDA selected eight proposals.
The winning bids include BrainsWay’s Deep Transcranial Magnetic Stimulation (DTMS) Device, virtual reality neuropsychological therapy from CognifiSense, and a pain therapy device from Avanos, among others. Developers will receive increased interaction with CDRH experts and expedited review.
Getting patients on board
As companies continue to develop new solutions to treat chronic and acute pain, they face huge scientific, project management, and public health hurdles. Pharma and biopharma companies must develop new, fast-acting, long-lasting formulas that control pain without addiction, secure venture funding for these drugs, and recruit patients willing to give up what’s proven to work for something that may or may not.
Patient recruitment strategy generally depends on the demographics of the target population and the condition under investigation. Thinking broadly, drug developers have a broad patient population to draw from. In 2017, doctors prescribed opioids to 58 of every 100 patients.
Of the millions of people prescribed opioids, only a fraction would make it through screening due to the drug’s intended indication and inclusion and exclusion criteria. Of the non-opioid drugs reported on clinicaltrials.gov, many list exclusion criteria such as alcohol consumption, dependence, unstable psychiatric condition, and use of NSAIDs within a specified time period, among other factors.
Non-opioid pain medication studies also have to overcome misconceptions among both doctors and patients. Doctors either may not know about a study or assume a patient doesn’t meet the criteria. Successful recruitment of physician-investigators may improve awareness and patient recruitment.
Patients also face multiple personal obstacles when choosing to participate. Prospective participants may decline to enroll due to concerns over time missed from work to visit a site, the burden of finding childcare, or getting transportation to a site. Cost is another determining factor. CDC reports that counties with higher prescribing rates tend to have more people who are uninsured or unemployed.1 And a study published in JAMA Internal Medicine showed lower income, mostly white regions in California received about 28% more opioid prescriptions than higher-income, more diverse areas.2
If insurance only covers a portion of the costs, or if a prospective participant doesn’t have insurance, he or she may opt out for financial reasons. And although Medicare covers routine costs from clinical trials, patients may not be aware of that benefit.
We also have the fear factor to reckon with. Whether they’re preparing for surgery or managing chronic pain, most patients know opioids work. How do we convince them to move away from what’s known to what’s not known?.
At Biorasi, we help pharmaceutical and biotech companies overcome these obstacles. Over the years, Biorasi has established itself as a pioneer in devising innovative methods for challenging patient recruitment situations. We’ve conducted outreach in community-based settings, developed partnerships with disease-related foundations, and recruited patient navigators to guide patients through the clinical trial process. We also have access to a large and diverse number of sites to help sponsors enroll the right number of patients that meet the chosen criteria.
Interested in learning more about our leadership in pain management? Talk to one of our clinical experts.
1. Centers for Disease Control and Prevention. Prescription Opioid Data. Last updated: December 19, 2018.
2. Friedman J, Kim D, Schneberk T, et al. Assessment of Racial/Ethnic and Income Disparities in the Prescription of Opioids and Other Controlled Medications in California. JAMA Intern Med. 2019;179(4):469–476. doi:10.1001/jamainternmed.2018.6721