Dear Biopharma: Give Us Better Therapies for Pain


Xconomy Boston — 

The CDC released on March 15th new guidelines that advise strict limits on the prescription of opioids for pain. These guidelines respond to a stunning increase in deaths and addiction related to the prescription of opioids like OxyContin and Percocet. The CDC recommended against providing patients more than a seven-day supply of opioids for acute pain and to avoid prescribing high doses of these medications whenever possible. President Obama has also requested $1.1 billion in funding for medication-assisted treatment, overdose reversal with naloxone, and other measures to fight this epidemic.

Overdose deaths from prescription opioids have quadrupled since 1999, reaching over 14,000 deaths in 2014. Use of prescription opioids is also driving an explosion in heroin use—80 percent of new heroin users started by using prescription opioids before turning to heroin.

Doctors have not been vigilant enough about writing short prescriptions and monitoring for signs of abuse. Pharmaceutical companies, meanwhile, have contributed to the problem by encouraging use of opioids for chronic conditions such as arthritis and migraines, even though data supporting their long-term efficacy in these conditions is weak.

I have several patients who take opioids daily and have been doing so for years. They are at risk for chemical dependence, hypersensitivity to pain, and overdose as a result. While I hope to taper them off opioids, doing so is extremely challenging. The existing non-opioid medication options, particularly NSAIDs like ibuprofen, are not potent enough for many patients and carry their own risks.

It is true that doctors should not prescribe so many opioids. But to reduce prescription rates, we need better non-opioid pain therapies to offer our patients.

Most drug development efforts in this field have aimed to take existing opioid drugs, such as oxycodone, and create new formulations designed to deter abuse. Collegium Pharmaceutical, for example, has developed a technology that exhibits multiple abuse-deterrent properties that could reduce the risk of snorting or injecting the drug. Collegium is awaiting an FDA ruling on its new drug application for its lead drug, Xtampza, an extended-release oxycodone.

Nektar Therapeutics, meanwhile, has developed a novel opioid molecule, NKT-181, that enters the brain at a 90 percent slower rate than traditional opioids. This property reduces the euphoric effect of the drug, thereby diminishing its abuse potential. The drug, which is now in phase 3 trials, also appears to have a lower risk of overdose because it suppresses breathing less than other opioids.

These medications offer clear advantages over traditional opioids, but they still carry some risk of addiction, abuse, and overdose. What we need most are non-opioid medications that effectively treat severe pain. There are a few such drugs in development, although not enough.

Tanezumab, a monoclonal antibody against nerve growth factor developed by Pfizer in partnership with Lilly, is in phase 3 trials for osteoarthritis and chronic low back pain. The drug has shown good efficacy, but with some concerning side effects that led the FDA to place a temporary hold on research (which is now lifted). As a biologic, the drug must be administered intravenously or subcutaneously and will carry a hefty price, potentially limiting its impact. Biologics targeting calcitonin gene-related peptide are also being developed, principally to treat migraines.

Small molecules, which can be taken by mouth and are cheaper to manufacture, would be much more convenient and affordable for pain patients. NeurAxon is developing small-molecule inhibitors of neuronal nitric oxide synthase for use in migraine and nerve pain that occurs after a shingles infection. The company has drugs in phase 2 trials.

Angiotensin type II receptor blockers represent another small-molecule drug class showing promise for pain treatment. Novartis in 2015 paid $200 million upfront for Spinifex Pharmaceuticals, whose lead candidate is a drug in this class in phase 2 trials for nerve-related pain.

Raxatrigine, a small molecule that blocks sodium channels on nerve cells, is also in phase 2 trials for nerve-related pain. And several other companies, including Quartet Medicine, have early-stage programs for chronic or acute pain.

It is clear that the pipeline of safer pain therapies is too thin to address all pain conditions. The need is particularly great for non-opioid small molecules that can be used in chronic pain. I hope the new guidelines from the CDC will serve as a starting gun in a race among drug companies to develop non-opioid pain therapies that work for my patients.

Alex Harding is a resident physician in the primary care track of Internal Medicine at Massachusetts General Hospital. He has no financial interests to disclose. Follow @alexharding7

Alex Harding is a practicing internist at Massachusetts General Hospital and an associate at Atlas Venture, a biotechnology venture capital firm. Follow @alexharding7

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