Two phase III trials that found treatment with the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib)

In Clinical Trials by Simon Crompton-ReidLeave a Comment

Two phase III trials that found treatment with the investigational Janus kinase (JAK) inhibitor INC424 (ruxolitinib) significantly reduced disease burden in patients with myelofibrosis, according to study results published by the New England Journal of Medicine (NEJM). The results of COMFORT-I and COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) were first presented at the 47th American Society of Clinical Oncology (ASCO) annual meeting in June 2011.

In the COMFORT-II trial, INC424 produced a volumetric spleen size reduction of 35 per cent or greater (roughly equivalent to a reduction in palpable spleen size by 50 per cent) in 28 per cent of patients compared to 0 per cent of patients in the best available therapy (BAT) group at 48 weeks (p<0.001).

At week 24, 32 per cent of patients treated with INC424 demonstrated a 35 per cent or greater volumetric spleen size reduction compared to 0 per cent of patients treated with the BAT (p<0.001) for the key secondary endpoint. Additionally, INC424 was associated with improvements in myelofibrosis symptoms at each evaluation as compared to the BAT.

Continuous INC424 therapy also provided a marked and durable improvement in overall quality of life measures, functioning and symptoms, including appetite loss, dyspnea (shortness of breath), fatigue, insomnia and pain, at week 48, compared to a worsening of symptoms in BAT-treated patients. INC424 showed modest toxicity as compared with the BAT, with increased frequency of anemia and thrombocytopenia.

The most frequently reported serious adverse event (SAE) was anemia for both groups (INC424, 5 per cent; BAT, 4 per cent). Pneumonia was the only SAE reported in >=5 per cent of patients in either group (INC424, 1 per cent; BAT, 5 per cent). These findings are consistent with previous investigation of INC424.

COMFORT-II is a randomized, open-label, phase III trial of INC424 versus the BAT that enrolled 219 patients with primary myelofibrosis (MF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) in 56 study locations. Two-thirds of the patients enrolled received INC424 (starting dose 15 or 20 mg twice daily) and one-third received the investigator-selected BAT.

Novartis licensed INC424 from Incyte for development and potential commercialization outside the US. Incyte has retained rights for the development and potential commercialization of INC424 in the US. Both the European Commission (EC) and the US FDA granted INC424 orphan drug status for myelofibrosis.

Christopher Fang, Worldwide Director, Clinical Research & Medical affairs, DePuy Spine, Johnson & Johnson, USA, will be presenting at Pharma Trials World Asia 2012 this March on "Utilising clinical technology to accelerate your trial progress."

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