FDA worried about Pfizer/Lilly pain drug safety ahead of key meeting

Red spine and vertebral column of a human skeleton

After a long and troubled development the fate of Pfizer/Lilly’s tanezumab painkiller injection is in the balance ahead of a key meeting of advisers later this week. 

Safety has been an issue throughout development and in 2012 the FDA put tanezumab on clinical hold because of a class-related issue with joint destruction, which was finally lifted in 2015.

Tanezumab is now the most developed of the two remaining drugs in development in the NGF class, in pain caused by osteoarthritis.

But first FDA arthritis and safety experts will run the rule over trial evidence at a joint meeting – and a review prepared by FDA staffers ahead of the meeting on Wednesday and Thursday does not bode well.

While the committee’s decision is not binding, the FDA usually follows the advice of its experts when making a final decision on whether to approve drugs.

According to the document the FDA reviewers are “not sufficient to mitigate the risk of RPOA [Rapidly Progressive Osteoarthritis Rheumatology]” and may not even ensure the “benefits of tanezumab outweigh the risks of RPOA”.

The FDA pointed out that of the small number of patients developing RPOA, 15% needed total joint replacement and after early signs of trouble 60% needed their joints replacing.

In one large study mentioned in the document of tanezumab 11 patients out of 998 on the highest dose developed RPOA (1.1%) while at the lower dose, three out of 1,002 patients developed the condition.

Stopping the drug after progression to more serious disease does not appear to be effective in preventing further damage to joints, the FDA added.

There is also a concern about mild nerve pain, with the most common from this being carpal tunnel syndrome.

Balanced against this is a “modest” benefit and “no convincing evidence of a superior efficacy” compared with non-steroidal anti-inflammatory drugs (NSAIDS), the FDA added.

Regeneron and Teva’s fasinumab is the only other serious contender from the class, which is in late stage clinical development.

Johnson & Johnson axed development of its rival fulranumab five years ago and returned rights to Amgen, although at the time the company said the decision was not based on any emerging safety concerns.

Amgen doesn’t seem to have done anything with fulranumab since – it is not mentioned the company’s pipeline round-up – meaning the search for a new class of non-addictive painkillers may continue for some time.