The current lack of innovation in the pain space is hurting society - MedCity News

Current pain medications are addictive (opioids) or potentially liver-damaging (acetaminophen/tylenol) or kidney-damaging with significant gastrointestinal toxicity (non-steroidal anti-inflammatory drugs, NSAIDs).

Three landmark events in November 2022 highlight the need for innovation in safer pain management

First, in its updated Clinical practice guidelines for prescribing opioidsthe Centers for Disease Control and Prevention (CDC) is encouraging doctors to once again use opioids on a case-by-case basis for moderate to severe acute and chronic pain, in response to a crisis of untreated pain left over from the previous 2016 guidelines. Second, Regeneron has announced that it has stopped developing its nerve growth factor (NGF) inhibitor. for knee and hip osteoarthritis (OA) pain in a phase 3 study. This follows cases of a rapidly progressive form of OA requiring joint replacement.

Pfizer also discontinued its NGF pain program in 2021 due to similar safety concerns and unproven efficacy in pain versus NSAIDs alone. Targeting NGF against pain has never made much sense scientifically because it has a weak mechanism of pain action. What’s more, the development of an antibody therapy—rather than a small molecule for the pain space—leaves unanswered how limited U.S. health care dollars will cover the costs of a disease affecting more than 50 million Americans. And thirdly, Australian regulators are considering restricting the sale of acetaminophen this month after an independent expert report raised concerns about teenage overdoses, with women at highest risk. Proposals include limiting the amount bought over the counter so it is not “stacked” at home and requiring a prescription for under-18s.

Risk of hepatotoxicity of acetaminophen

Acetaminophen has a narrow therapeutic index, and hepatotoxicity is a significant risk with intentional overuse (eg, suicide attempt) and unintentional overuse (eg, consuming acetaminophen without realizing that it is present in various prescription and over-the-counter formulations) . In addition, its use in patients with impaired liver function, especially in the elderly, poses a significant risk of liver damage. Despite ongoing regulatory and educational efforts over the past several years to improve patient safety, intentional and unintentional acetaminophen overdose remains a major public health problem. Each year in the US approx 30,000 patients were hospitalized due to acetaminophen hepatotoxicity. A safer, non-NSAID alternative to acetaminophen is needed to address acetaminophen hepatotoxicity. Indeed, much like the discussions currently taking place in Australian regulators, a decade ago The FDA has issued a boxed warning highlighting the potential for severe liver damage. In Canada, acetaminophen toxicity persists despite labeling changes introduced in 2009 and 2016. These labeling standards were made to communicate the dangers of acetaminophen overdose and promote safe use. However, monthly hospital and ICU admission rates for accidental acetaminophen overdose were unchanged between April 2004 and March 2020.

Renal, cardiovascular, and gastrointestinal (GI) risks with NSAIDs

Risks of overuse of NSAIDs include increased blood pressure, kidney toxicity leading to acute kidney injury (AKI), and gastrointestinal damage. In fact, most chronic NSAID users have significant small bowel damage and bleeding. In the treatment of acute pain in the postoperative period, the use of NSAIDs leads to AKI and complications in patients undergoing surgery. There are several patient populations at risk for NSAID-induced AKI. Patients vulnerable to NSAID renal toxicity leading to serious adverse outcomes include patients with chronic kidney disease. Exposure to NSAIDs was associated with an approximately 1.6-fold increase in the odds of developing AKI in hospitalized pediatric patients and in the elderly.

Prevalence of pain and opioid use disorder (OUD) in the United States

OUD affects 2.1 million people in the US, 16 million people worldwide and over 120,000 deaths per year attributable to opioids. OUD includes the abuse of prescription painkillers and the use of heroin. Prescription painkiller abuse was the second most common form of illicit drug use in the US in 2018 after marijuana use, with 3.6% of the population abuses painkillers.

In the US, pain affects more adults than diabetes and cancer combined, costing the health care system an estimated $635 billion annually. in September 2022, published by CDC preliminary data showed that drug overdose deaths exceeded 107,000 in the previous year, the largest increase in a year. Drug-related deaths are disproportionately higher in the younger population than in the older population. Although opioid prescriptions have been declining since 2012, and most overdose deaths are now from fentanyl sold on the street, often mixed with other drugs, 14,000+ of those deaths are from prescription painkillers. Furthermore, 500,000 emergency visits per year attributed to prescription painkiller abuse.

Future innovation in pain relief

Multiple randomized clinical trials have shown that combination non-opioid therapies (high-dose acetaminophen and NSAIDs) are at least as effective as opioids for many common types of moderate to severe pain. Although pain is subjective, multiple well-conducted clinical trials have demonstrated the high reproducibility of clear endpoints. Therefore, pain clinical trials have a track record of demonstrating efficacy when well designed and executed.

The prevalence of OUD, including high overdose rates in the US and the toxicity profiles of currently available drugs, underscores the need for a new strategy.

Recognizing the need for new non-opioid therapies, the National Institutes of Health (NIH) created the Helping to End Addiction Long-Term (HEAL) initiative in 2018. The financial, scientific and commercialization support of this program is an important jump-start toward pain relief innovation. The future of safer pain management will come as biopharmaceuticals, and the investor community appreciates the significant opportunities in supporting scientifically rigorous and clinically validated lead assets for safer pain management.

Photo: Erhui1979, Getty Images

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