Novartis’ niche-and-expand strategy for Ilaris has hit a big bump. An FDA expert panel strongly rejected the antibody for treatment of gout, raising concerns about long-term safety (Event – Novartis hoping to keep growing Ilaris with gout approval, June 14, 2011).
The tone of the advisory committee’s discussions suggest that the agency will want further safety studies, and then probably consider the drug only for the most severe patients. Given that its currently authorised indication of cryopyrin-associated periodic syndrome (CAPS) - a very rare disorder - accounts for a small share of its forecast 2016 sales, the Swiss group will face some key development choices should the regulator follow the adcom’s guidance.
Effective, but is it safe?
Ilaris is intended to treat acute spells of gout, an accumulation of uric acid in the body that manifests itself by crystallising in the joints, leading to inflammation and pain. Known generically as canakinumab, the antibody binds to human interleukin-1 beta, inhibiting the pro-inflammatory signalling of the protein.
Novartis had tested Ilaris in the hope of obtaining approval for treatment and prevention of outbreaks of acute gout flares in patients unable to take colchicine or non-steroidal anti-inflammatory medicines, the usual protocol for flares. This that would have given it potentially wider application among the estimated 3.9% of American adults who suffer from gout.
However, in an end-of-phase II meeting, the FDA told the company the data probably only supported a treatment indication, a much smaller indication. The panel agreed, voting unanimously against recommending it as a drug to prevent, delay and reduce the frequency of future outbreaks.
The panellists agreed that Ilaris was effective in treating outbreaks, but said the trial data was not sufficient to demonstrate long-term safety: only 43 of 454 patients had received three or more injections. Among the safety concerns raised by agency staff were greater rates of infection, a decline in creatinine clearance, elevated uric acid levels in the blood and hypertrigylceridaemia.
Now with an 11-1 vote against approval that will almost certainly lead to a no from the agency in the third quarter. In response to the hearing, Novartis signalled that it will continue to try to identify the patients who might benefit.
Currently forecast as Novartis’ 15th biggest drug in 2016, Ilaris had been expected to derive one-third of its $663m in sales that year from gout, according to EvaluatePharmaconsensus data. A rejection would drive that forecast down, especially if the agency asks for time-consuming trials that push its launch out two years or more. CAPS, the currently marketed indication, is expected to earn just 4% of that total forecast sales, a not surprising result given a prevalence of just 1 in 1 million, or about 300 Americans.
The antibody has already hit a bump in its development process: abandonment of phase II trials for rheumatoid arthritis, potentially its biggest indication. Phase III trials are still ongoing in juvenile idiopathic arthritis and atherosclerosis, and phase II trials in osteoarthritis, which is forecast as its biggest opportunity.
The negative news for Ilaris also is a big disappointment for gout patients and specialists, who only in recent years have seen new treatments hit the market to supplement older medications, cholcicine and allopurinol (Therapeutic focus - Gout pipeline looks thin but holds promise, May 26, 2011).
Ilaris’ struggles may represent opportunity for Regeneron Pharmaceuticals and Arcalyst. Also an interleukin-1 antagonist used to treat CAPS, it has successfully completed phase III trials in preventing gout flares and expects to file for approval sometime in the middle of this year.
Should the FDA affirm the adcom decision, as is likely, the question for Novartis executives will be whether to spend money on additional clinical trials for an opportunity that seems to be shrinking at every critical catalyst. With big musculoskeletal and cardiovascular opportunities out there, the decision may very well be no.