The only surprising thing about Novartis’ complete response letter for gouty arthritis treatment Ilaris is that it came a few days later than many had expected.
As widely predicted following an 11-1 vote against approval at an FDA advisory committee back in June, the US health authority declined yesterday to approve the drug, throwing a big spanner into the works for Novartis’ strategy to expand the drug into larger indications. The big question now is what Novartis will do with Ilaris (Ilaris misses chance in gout, June 22, 2011).
Although the Swiss group has said that it will carry on with development of Ilaris in inflammatory diseases where interleukin-1 beta plays a key role, with the prospect of big expensive trials ahead of it, for what might ultimately be a small patient population, gout is unlikely to be one of those diseases.
This setback is the second for the drug, which was abandoned in rheumatoid arthritis in phase II. It now leaves Ilaris, which has already been approved in the niche indication of cryopyrin-associated periodic syndrome, looking at juvenile idiopathic arthritis and osteoarthritis.
It now seems a long time since the likes of Credit Suisse were forecasting sales in gout of $400m, although in reality it was only back in April. But with the bad news already priced into the shares following the negative response from the advisory committee shares in Novartis actually rose yesterday in better markets.
As for its next move, Novartis might decide the fate of Ilaris following the outcome of European ruling in gout due by the end of the year, although the drug is almost certain to run up against similar safety concerns again.
What derailed Ilaris’ US approval was that less than 10% of trial patients had received the drug more than three times. Given that the drug is filed for gout flares, use over a lifetime would have easily exceeded this. Of particular worry to the regulator were the greater rates of infection and raised uric acid levels in the blood.
The FDA’s rejection highlights the fact that companies can no longer get away with limited safety data, unless the indication they are going after has few treatment options available.
While this is not a major blow to Novartis, it has failed to validate the group’s start small and expand philosophy. But one group it might make a difference to is the companies looking at new and novel gout treatments in a very thin field (Therapeutic focus - Gout pipeline looks thin but holds promise, May 26, 2011).
|Annual Sales WW - ($)|
|Status||Product||Generic Name||Company||Pharmacological Class||Launch WW||2010||2016|
|Filed||Ilaris||Bristol-Myers Squibb/Novartis/ Pharmaceuticals||Anti-IL-1-beta||31/03/2012||26||605|
|Arcalyst||rilonacept||Regeneron Pharmaceuticals||IL-1 antagonist||30/09/2012||25||97|
|Phase III||FYX-051||topiroxostat||Fuji Yakuhin/Suzuken Group||Anti-gout preparation||-||-||-|
|BCX-4208||-||BioCryst Pharmaceuticals||Purine nucleoside phosphorylase (PNP) inhibitor||31/12/2015||-||30|
|Phase II||RDEA594||lesinurad||Ardea Biosciences||URAT1 inhibitor||31/12/2014||-||238|
|RDEA806||-||Ardea Biosciences/Valeant Pharmaceuticals International||Non-nucleoside reverse transcriptase inhibitor (NNRTI)||31/12/2013||-||-|
|NU1618||tranilast||Kissei Pharmaceutical/Nuon Therapeutics||Xanthine oxidase inhibitor||-||-||-|
|MBX-102/JNJ 39659100||arhalofenate||Johnson & Johnson/Metabolex||Selective PPAR gamma modulator (SPPARM)||-||-||-|
|Phase I||Pegadricase||pegadricase||Polaris Group/3SBio||Urate oxidase||-||-||-|
|LC350189||-||LG Life Sciences||Anti-gout preparation||-||-||-|
|XOMA 052||gevokizumab||XOMA/Les Laboratoires Servier||Anti-IL-1-beta MAb||-||-||-|