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CHMP recommends label update for Esbriet in idiopathic pulmonary fibrosis

Roche has announced that Esbriet (pirfenidone) has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for an update to its European prescribing information, strengthening the efficacy claims and supporting the well-established safety profile based on the additional data from the phase III ASCEND trial.

Approved in the EU in 2011, Esbriet is indicated for the treatment of adults with mild to moderate IPF.

The CHMP recommendation includes data from the phase III ASCEND study, which showed that the proportion of patients with =10 percent decline in forced vital capacity (FVC) – a measure indicative of the risk of mortality in IPF – was significantly reduced in patients receiving Esbriet compared with patients receiving placebo at one year.

Also included in the label update is a pre-specified pooled analysis from ASCEND and the two phase III CAPACITY trials that showed that the risk of all-cause mortality was reduced by 48 percent in Esbriet-treated patients compared with the placebo group at one year.

The pooled analysis also showed that the risk of treatment-emergent IPF-related mortality in the Esbriet group compared to placebo was reduced by 68 percent in the pooled population at one year.1

"This recommendation from the CHMP acknowledges the compelling evidence for Esbriet to reduce the progression of this deadly disease in people with IPF," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Roche.

"The inclusion of the ASCEND data in the European prescribing label for Esbriet will provide important additional information for physicians and patients."

Following the CHMP positive opinion, the EU prescribing information will now be updated to include the ASCEND data. On October 15, the FDA approved Esbriet in the United States, under the Breakthrough Therapy Designation.

IPF is a fatal disease caused by irreversible, progressive scarring (fibrosis) of the lungs, which makes breathing difficult and prevents the heart, muscles and vital organs from receiving enough oxygen to work properly.8 The disease can advance quickly or slowly, but eventually the lungs will harden and stop working altogether.8 IPF’s rapid decline is often worse than many malignancies, including breast, ovarian and colorectal cancers.9

In August 2014, Roche and InterMune announced that they have entered into a definitive merger agreement for Roche to fully acquire InterMune. The transaction was completed in September 2014.

"This label amendment reinforces Esbriet’s role as an important treatment option for patients with IPF," said Jonathan Leff, M.D., Executive Vice President of Research and Development at InterMune. "Patients and their caregivers can remain confident in the safety and efficacy profile of Esbriet."

ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in IPF) evaluated the safety and efficacy of oral pirfenidone compared with placebo in 555 patients worldwide with IPF. Patients were enrolled at 127 centers in the United States, Australia, Brazil, Croatia, Israel, Mexico, New Zealand, Peru and Singapore.

The primary endpoint was defined as a change in forced vital capacity (FVC), or the measure of how well the lungs work based on the amount of air exhaled with force after inhaling as deeply as possible. A 10 percent or more decline in FVC in an IPF patient is considered clinically meaningful and strongly predictive of higher risk of mortality.

The ASCEND study results highlighted the following:

  • At week 52, 17 percent of patients receiving Esbriet showed a decline of 10 percent or more in predicted FVC as compared to 32 percent of patients receiving placebo (p<0.001).1Additionally, 23 percent of patients receiving Esbriet experienced no decline in FVC at week 52, compared with 10 percent receiving placebo.
  • Pirfenidone also significantly reduced the decline in six-minute walk distance (p=0.036) and improved progression-free survival (PFS) (p=.0001).
  • A pre-specified pooled analysis from ASCEND and the two phase III CAPACITY trials through one year showed that the risk of all-cause mortality was reduced by 48 percent in Esbriet-treated patients compared with the placebo group (HR 0.52, p=0.01).
  • The pooled analysis also showed that the risk of treatment-emergent IPF-related death in the Esbriet group compared to placebo was reduced by 68 percent in the pooled population at one year (HR 0.32, p=0.006).
  • Pirfenidone showed a favorable safety profile and was generally well tolerated.
  • Adverse events that occurred during the study included amongst others gastrointestinal and skin related events and both were more common in the pirfenidone group than in the placebo group. These events were generally mild to moderate in severity, reversible, and without clinically significant consequences.
  • There were fewer serious adverse events in the pirfenidone group (19.8 percent) than in the placebo group (24.9 percent). Adverse events led to the discontinuation of study treatment in 14.4 percent in the pirfenidone group and 10.8 percent in the placebo group. The most common adverse event resulting in treatment discontinuation was a worsening of IPF in 1.1 percent of patients in the pirfenidone group and 5.4 percent in the placebo group.