Novartis Unveils Positive Phase II Results For Genetic Auto-inflammatory Disease Candidate

Interleukin 1b blocker ACZ885 achieves complete clinical remission in seven days for Cryopyrin-Associated Periodic Syndrome Patients.

Novartis reported promising Phase II data for ACZ885, its human monoclonal antibody interleukin 1b blocker in trials for Cryopyrin-Associated Periodic Syndromes, April 8 during the International Congress on Familial Mediterranean Fevers and Systemic Autoinflammatory Diseases in Rome.

ACZ885, which has moved into Phase III, is being developed for CAPS in the U.S. and European Union, where it has orphan drug status. The compound also is in Phase II for systemic onset juvenile idiopathic arthritis, for which it has orphan status in the EU only.

In a Phase II study of 20 patients with CAPS, a group of serious, life-long diseases including Muckle Wells Syndrome, ACZ885 produced an improvement in symptoms within one day and complete clinical remission within seven days. On average, clinical remission lasted 115 days, Novartis said.

CAPS diseases generally present immediately after birth and involve symptoms such as fever, joint pain and rashes, which can lead to severe complications. Phillip Hawkins, a lead investigator of the Phase II study, said no treatment had worked until patients were administered anikinra (Amgen's Kineret ), the first IL-1 inhibitor to reach the market, in 2002.

"I've been working with patients with Muckle Wells Syndrome for about 10 years, and we have treated them with many different anti-inflammatory drugs, indeed almost every inflammatory drug of the type that are commonly used in rheumatoid arthritis, without any success whatsoever," Hawkins, a professor at England's National Amyloidosis Centre, told "The Pink Sheet" DAILY.

"We performed the first studies with ACZ885, which had an extremely dramatic effect leading to complete resolution of all the inflammation and symptoms within literally hours of administering," he added. "This has had a very prolonged benefit in all of the patients that were treated, so it's really a complete response of all of the symptoms of the disease."

Initially, patients were dosed intravenously every six months, Hawkins explained, after which they were given a dosage by subcutaneous injection every two months. Adults receive a 150 mg dose, while children are dosed with 2 mg for each kilo of body weight.

Novartis also is investigating the compound, which blocks only IL-1B, for rheumatoid arthritis, using a tailored approach with biomarkers to predict response to treatment. The firm claims that if this approach succeeds, suitable patients will have access to a personalized approach to treating RA.

In the meantime, the Phase III study of ACZ885 in CAPS is well underway; Hawkins told the DAILY the first of about 40 to 50 participants will complete treatment in May, and the trial should complete in about six months. The primary endpoint is clinical benefit measured by a composite symptom score, he said.

While Novartis is targeting a general CAPS indication, ACZ885 will not be the first therapy for Muckle Wells Syndrome to reach the market. Regeneron recently launched Arcalyst (rilonacept) for that disease and another CAPS indication, familial cold auto-inflammatory syndrome (¹ (Also see "Regeneron’s Ultra-Orphan Arcalyst Hits The Market With A Rare Price" - Pink Sheet, 28 Feb, 2008.)).

Arcalyst was launched with a wholesale acquisition cost of $250,000 per year due to its ultra-orphan indication.

The path forward for ACZ885 will be paved by Novartis' new head of global development, Trevor Mundel, who succeeds James Shannon (² (Also see "Drug Development Chief Departs Beleaguered Novartis" - Pink Sheet, 20 Mar, 2008.)).

-Joseph Haas ([email protected])