FDA starts review of Pfizer, Lilly’s non-opioid painkiller

After years in development, the FDA has started its review of Pfizer and Eli Lilly’s new painkiller tanezumab, one of two remaining drugs in the ill-fated nerve growth factor (NGF) inhibitor class.

The US regulator is carrying out a standard 10-month review of tanezumab as a treatment for chronic pain due to moderate-to-severe osteoarthritis (OA) in those who can’t get sufficient pain relief with other analgesic drugs, with a verdict due in December.

Tanezumab and Regeneron/Teva’s fasinumab are the last survivors in a class that at one time was predicted to have multibillion dollar potential thanks to the promise of sidestepping the addiction problems associated with opioid analgesics.

Pfizer says there are about 27 million Americans that suffer from osteoarthritis and 11 million of those have moderate to severe disease. Of these, 80% have tried and failed three or more analgesics.

Tanezumab’s marketing application reveals the long path taken by Lilly and Pfizer on their way to market, with data from 39 phase 1 to 3 trials involving around 18,000 subjects included in the dossier.

The two partners have wrestled with a persistent safety concern with NGF inhibitors – rapidly progressing joint destruction – that has already claimed multiple casualties among other drugs in the class, including candidates from Johnson & Johnson/Amgen, AstraZeneca/Medimmune and AbbVie.

With safety a lingering concern, it’s no surprise that the FDA has indicated it will call an advisory committee meeting to discuss tanezumab’s marketing application.

Tanezumab has posted positive trial data in osteoarthritis and chronic lower back pain, although lower doses of the NGF inhibitor were ineffective and the drug had more adverse safety events than comparators. It is also being developed for cancer pain due to bone metastases.

Pfizer and Lilly have filed for approval of a 2.5 mg subcutaneous dose, which had mixed results in the osteoarthritis study reported last year. A higher 5 mg dose was associated with a greater risk of rapidly progressing osteoarthritis.

Pfizer’s head of bioscience Angela Hwang said on the company’s fourth-quarter results call in January that the filing of the 2.5 mg dose followed “close collaboration” with the FDA.

“There is just a huge amount of unmet need in this patient population. Patients are cycling through a number of pain medications, and there…is an incredible need for new options,” she added.

Regeneron and Teva meanwhile are still waiting for the results later this year from a phase 3 programme for fasinumab in osteoarthritis pain, including long-term safety studies comparing the drug to non-steroidal anti-inflammatory drugs (NSAIDs) like naproxen.

Lilly has made chronic pain a key area of focus for its R&D, and last year signed a $1 billion licensing deal with Centrexion Therapeutics for CNTX-0290, a small-molecule somatostatin receptor type 4 (SSTR4) agonist in phase 1 testing that also has potential as a non-opioid painkiller.