Physicians have long relied on opioids and similar pharmacologic therapies for pain, despite known risks of side effects or substance use disorders. There is a pressing need for safer and more effective options, yet current efforts to develop new therapeutics have not made it past phase 2 or phase 3 trials. Instead, drug manufacturers are concentrating on reformulating existing medications to reduce dependence.
In a recent a retrospective cohort study published in Mayo Clinic Proceedings, Thomas J. Hwang of the Program on Regulation, Therapeutics, and Law (PORTAL), division of pharmacoepidemiology and pharmacoeconomics, department of medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and coauthors said “new policies, such as increased funding for basic pain research, may help address the urgent need for new therapies for pain.”1
Coauthor Michael S. Sinha, MD, JD, MPH, a research fellow in the Harvard-MIT Center for Regulatory Science at Harvard Medical School, is concerned about the effect of reformulated medications on the cost of and access to pain medications. “Abuse-deterrent formulations of opioids, have increased the cost of pain medications while delaying market entry of generic equivalents that are often quite safe when used as directed,” he said in an email to Cancer Therapy Advisor.
Dr Sinha and colleagues conducted 4 analyses to characterize trends in research and development for new pain drugs between January 1, 2000, and December 31, 2015. They identified 119 investigational pain drugs that entered phase 1 testing. Among those that started phase 1 trials between 2000 and 2013, more than half progressed to phase 2, but only 10 then subsequently progressed to phase 3 trials. In comparison, 141 reformulations of existing agents started various phases of clinical testing during that same period.
By 2012, more reformulated drugs than new analgesics entered clinical development.
Pain management and palliative care experts have been frustrated with the lack of development of new pain drugs. “It’s more than 100 years and we’re still using opioids predominantly for pain, and there really hasn’t been much of an advance during that time,” said Egidio Del Fabbro, MD, director, palliative care program, Massey Cancer Center, Virginia Commonwealth University.
“There certainly aren’t any big phase 3 trials that have demonstrated benefit in any new kind of analgesic,” he told Cancer Therapy Advisor. Dr Del Fabbro said much of the current research has been geared towards noncancer related pain. However, those with cancer-related pain have unique needs and may require higher doses, placing them at increased risk for substance use disorder.
According to a recent consensus study report from the National Academies of Sciences, Engineering and Medicine, “Excessive opioid prescribing not only puts patients at risk for opioid addiction and overdose; leftover prescription opioids may also be misused by family members.”2
Approximately 1 in 5 cancer patients is at risk of adverse outcomes from opioid use including nonmedical opioid use (NMOU), prolonged use, or increased health utilization, according to Dr Del Fabbro.3 However, if physicians use them judiciously, the risks can be mitigated, including side effects and the potential for addiction.
It’s not unreasonable to ask physicians to assume responsibility for risk management of opioids, given the current abuse crisis. But patients experiencing pain from cancer should not be lumped together with those with pain from other causes, such as postsurgical pain or chronic joint pain, according to James D’Olimpio, MD, director, supportive oncology/cancer pain and symptom management at Northwell Health Cancer Institute, in Long Island, New York. “Cancer pain has a specific type of physiology; a specific type of approach,” he told this publication.