Clinical Trials

Date: 2011-12-13

Type of information:

phase: 3

Announcement: results

Company: Novartis (Switzerland)

Product: INC424 (ruxolitinib)

Action mechanism: INC424 is an oral inhibitor of the JAK1 and JAK2 tyrosine kinases.

Disease: myelofibrosis

Therapeutic area: Cancer - Oncology - Blood diseases

Country: USA, Canada and Australia.

Trial details:

COMFORT-I Study Details for Symptom and Overall Survival Analyses
Patients were randomized to start INC424 or placebo at doses of 15 mg or 20 mg PO BID, depending on baseline platelet count (100-200 X10⁹/L or >200X10⁹/L, respectively). A total of 309 patients were randomized, 155 to INC424 and 154 to placebo. The dose was optimized for efficacy and safety during treatment.

The COMFORT-I study was conducted by collaboration partner Incyte Corporation in the US, Canada and Australia.

Latest news:

Novartis has announced additional results from two pivotal Phase III trials evaluating Janus kinase (JAK) inhibitor INC424 (ruxolitinib) in myelofibrosis. These data demonstrate the important potential role of INC424 in treating patients with myelofibrosis, a life-threatening blood cancer characterized by bone marrow failure, enlarged spleen (splenomegaly) and debilitating symptoms.

Results are being presented at the 53^rd Annual Meeting of the American Society of Hematology (ASH) in San Diego. A post-hoc analysis from the COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study evaluated patient-reported health-related quality of life (HRQoL) measures for INC424 versus best available therapy (BAT). The results showed a substantial improvement in HRQoL and myelofibrosis symptoms compared with baseline for patients receiving INC424 but remained the same or worsened for patients receiving BAT. Results were based on a broad range of validated QoL instruments.

In the COMFORT-I updated analysis, INC424 also demonstrated an overall survival advantage over placebo. A total of 13 INC424 and 24 placebo patients died during the study or during extended follow up after median follow up of 51 and 52 weeks, respectively, representing a hazard ratio (95% CI) of 0.499 (0.254, 0.98) (p=0.0395). Survival was estimated by the Kaplan-Meier method.

In the second Phase III study, COMFORT-I researchers evaluated INC424 versus placebo in symptom improvement and spleen volume reduction, as well as overall survival. Results showed that patients receiving INC424 had higher response rates based on reductions in spleen volume and Total Symptom Score (TSS). The TSS evaluated changes in symptoms, such as abdominal discomfort, pain under the ribs on the left side, early satiety, itching, night sweats and bone or muscle pain. These benefits were consistent across all patient subgroups, including myelofibrosis disease subtype, age, risk group, presence or absence of JAK2 mutation, hemoglobin, spleen size and TSS.

Is general: Yes