Tanezumab

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos. Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

Cristina Arias_Getty Images Another once-hopeful partnership has come to an end, as Eli Lilly and Pfizer announced Tuesday that they have ceased the development of tanezumab, a pain drug the two had been developing for osteoarthritis. The decision came following negative feedback from both U.S. and European regulators. Eli Lilly shared that the companies made the call after the U.S. Food and Drug Administration sent a complete response letter (CRL) that indicated the regulator would not approve tanezumab in its current form. Lilly made the announcement on its end in its Q3 Financial Results statement. Tanezumab, which has been under development since 2013, is a humanized monoclonal antibody that targets nerve growth factor (NGF), levels of which increase following injury, inflammation, or during chronic pain. The drug was intended to inhibit NGF, thereby preventing pain signals produced by muscles, skin and organs from reaching the brain. The companies had hoped the drug, which is part of a class called nerve growth factor inhibitors (NGF), could be an option for the treatment of moderate and severe osteoarthritis with opioids. Alternatives are clearly necessary, as the Centers for Disease Control and Prevention states that more than 760,000 Americans have died since 1999 from an opioid drug overdose. The decision will not come as a shock to those who have been following the drug's story. Despite showing definitively positive results in Phase III clinical trials, the FDA had raised critical safety concerns over tanezumab. Prime among them was the development of rapidly progressing osteoarthritis (RPOA), a condition both companies observed during clinical research. Lilly and Pfizer had sought to evaluate and monitor the drug and the associated safety issue under the FDA's Risk Evaluation and Mitigation Strategy (REMS). However, the agency stated in March that the "proposed REMS is not sufficient to mitigate the risk of RPOA and would not ensure that the benefits of tanezumab outweigh the risks of RPOA." The FDA's Joint Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee voted 19-1 that the REMS would not ensure the drug's benefits outweigh its risks. At the time, Ken Verburg, tanezumab development team leader at Pfizer Global Product Development said, "we continue to believe that tanezumab has a positive benefit-risk pro patients with moderate-to-severe osteoarthritis pain for whom current treatments are ineffective or not appropriate." Verburg added that these patients have not had a new class of medications available to them in more than a decade and are eager for new, non-opioid options. In September, the program took a hit when the European Medicines Agency's Committee for Medicinal Products for Human Use recommended against tanezumab's approval in Europe. Tanezumab is only the latest drug in the NGF class to fall victim to safety concerns. In 2010, Johnson & Johnson had a drug placed on hold over FDA concerns that it could be linked to a serious bone disorder. In 2016, the FDA put Teva and Regeneron's NGF inhibitor fasinumab on hold after one trial participant developed arthropathy, which is the rapid destruction of a joint. Fasinumab was being developed for the treatment of chronic lower back pain.