Alleviating osteoarthritis pain without the need for opioid drugs

Tanezumab, an investigational humanized monoclonal antibody developed by Pfizer (PFE) and Eli Lilly (LLY), met all three co-primary endpoints in patients with osteoarthritis (OA). The 16-week Phase 3 study, which evaluated subcutaneous administration of tanezumab in patients with OA, demonstrated that the patients who received two doses of tanezumab, separated by eight weeks, experienced a statistically significant improvement in pain, physical function and patients’ overall assessment of their OA as compared to those receiving placebo.

Tanezumab is part of an investigational class of pain medications known as nerve growth factor (NGF) inhibitors. In addition to OA pain, it is being evaluated for chronic low back pain (CLBP) and cancer pain (due to bone metastases). Tanezumab is a potential first-in-class, non-opioid treatment being evaluated for OA pain, CLBP and cancer pain (due to bone metastases). THE DRUG works by selectively targeting, binding to and inhibiting NGF. NGF levels increase in the body as a result of injury, inflammation or in chronic pain states.

By inhibiting NGF, tanezumab may help to keep pain signals, produced by muscles, skin and organs, from reaching the spinal cord and brain. Tanezumab has a novel mechanism that acts in a different manner than opioids and other analgesics which include nonsteroidal anti-inflammatory drugs (NSAIDs). In studies to date tanezumab has not demonstrated a risk of addiction, misuse or dependence.

Tanezumab was generally well tolerated, with approximately 1% of patients discontinuing treatment due to adverse events. Rapidly progressive OA was observed in tanezumab-treated patients at a frequency of less than 1.5% and was not observed in the placebo arm. There were no events of osteonecrosis observed in the trial. No new safety signals were identified.

“Worldwide, millions are living with osteoarthritis, which is a progressive disease that can significantly impact people’s everyday lives,” said Christi Shaw, Senior Vice President, Eli Lilly and Company and President of Lilly Bio-Medicines. “We look forward to continuing to advance tanezumab in our ongoing global Phase 3 development program, which includes six studies in approximately 7,000 patients with osteoarthritis, chronic low back pain and cancer pain.”

In June 2017, Pfizer and Lilly announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for tanezumab for the treatment of OA pain and CLBP. Tanezumab is the first NGF inhibitor to receive Fast Track designation, which is a process designed to facilitate the development and expedite the review of new therapies that treat serious conditions and fill unmet medical needs.

The Phase 3 OA study (A4091056)

A 16-week randomized, double-blind, placebo-controlled, multicenter, parallel-group trial evaluating the efficacy and safety of subcutaneous administration of tanezumab compared to placebo in patients with OA of the knee or hip. The trial included a 24-week safety follow-up period. In the study patients were enrolled with moderate to severe OA pain who had experienced inadequate pain relief with other treatment options for OA pain or were unable to take other pain medications.

A total of 698 patients were randomized to three treatment groups in a 1:1:1 ratio to receive two injections over the 16-week study, once every eight weeks. The first group received two doses of placebo. The second group received two doses of tanezumab 2.5 mg. The third group received one dose of tanezumab 2.5 mg followed by one dose of tanezumab 5 mg eight weeks later. Both tanezumab treatment arms met all three co-primary endpoints.

Side effects are low in the 2.5 mg and 2.5/5 mg arms of the trial, 0.4 percent and 1.3 percent of patients discontinued treatment because of adverse events. In the placebo arm, 1.3 percent discontinued treatments from adverse events. Side events included the common cold, pain in the extremities, and tingling or numbness.

Prohost Observations

Osteoarthritis affects a large percentage of people over 55 years old. More than 30 million people in the United States are affected by OA, which is a progressive disease that causes joint inflammation, degeneration, accompanied by joint stiffness, swelling and pain. Any product that can replace opioids in alleviating  inflammation and pain is more than welcome.

We will discuss this treatment for OA in the next Week in Review.

The discussion will be interesting as we will tackle Regeneron’s and Teva’s product Efalizumab which, like  Pfizer’s & Lilly’s tanezumab, also targets NGF.

It is a must read.

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