CHMP recommends label update for Esbriet in idiopathic pulmonary fibrosis, strengthening mortality benefit and reinforcing safety profile

• Pooled analysis of ASCEND and two CAPACITY phase III trials show 48 percent reduction in mortality risk at one year¹
• ASCEND data reinforces the Esbriet safety and efficacy profile¹
• Approximately 110,000 people in Europe have idiopathic pulmonary fibrosis (IPF), an irreversible, progressive, fatal lung disease^{2- 5}
• Only 20–40 percent of IPF patients survive five years after diagnosis^6,7

Basel, 24 October 2014 – Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today 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.¹ 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.^1,2 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.”

About ASCEND

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.¹⁰

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.¹
• Pirfenidone also significantly reduced the decline in six-minute walk distance (p=0.036) and improved progression-free survival (PFS) (p=.0001).¹
• 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).¹
• 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).¹
• Pirfenidone showed a favorable safety profile and was generally well tolerated.¹
• 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.¹
• 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.¹

About IPF

Approximately 100,000 people in the United States¹¹ and 110,000 in Europe have IPF,^2-5 an irreversible and ultimately fatal disease characterised by progressing loss of the ability of the lungs to absorb oxygen due to scarring.⁸ The cause is unknown and there is no cure. A limited number of patients with IPF undergo lung transplantation. IPF inevitably causes shortness of breath and destruction of healthy lung tissue.¹² The median survival time from diagnosis is two to five years, and the five-year survival rate is approximately 20 to 40 percent.^6,7 IPF typically occurs in people over the age of 45, and tends to affect slightly more men than women.^{12, 13}

About Esbriet

Esbriet is an oral medicine approved for the treatment of idiopathic pulmonary fibrosis. The mechanism of action of Esbriet is not fully understood, although it is believed to interfere with the production of Transforming Growth Factor (TGF)-beta, a small protein in the body involved in how cells grow and produce scars (fibrosis), and Tumor Necrosis Factor (TNF)-alpha, a small protein that is involved in inflammation. Earlier this year, the FDA granted Esbriet Breakthrough Therapy Designation based on these positive data and the serious and life-threatening nature of IPF. It has also been granted Orphan Drug designation in the United States and Europe.

Esbriet was developed for use by InterMune in the United States, Europe and other countries. On October 15, 2014, Esbriet received US FDA approval. It was granted marketing authorisation in the EU in 2011 for the treatment of adults with mild to moderate IPF in all 28 EU member countries, and has since been approved in Norway, Iceland and Canada. Pirfenidone has been marketed as Pirespa® since 2008 in Japan and since 2012 in South Korea by Shionogi & Co. Ltd. Under different trade names, pirfenidone is also approved for the treatment of IPF in China, India, Argentina and Mexico.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References:
1.King TE Jr. Bradford WZ, Castro-Bernardini S. A. N Engl J Med 2014; 370(22):2083−92
2.Eurostat News Release. Available at http://ec.europa.eu/eurostat. Accessed on 7 October 2014
3.Coultas DB et al. Am J Respir Crit Care Med 1994;150:967−997
4.Hodgson U et al. Thorax 2002; 57:338−342
5.Meltzer EB, Noble PW et al – Orphanet J Rare Dis (2008); 3:8−22
6.Bjoraker JA et al. Am J Respir Crit Care Med 1998;157:199−203
7.Collard HR et al. Am J Respir Crit Care Med 2003; 168:538–542
8.American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med 2002; 165:277−304
9.Cancer Facts and Figures 2009, American Cancer Society. PAH data source: Hamilton, N. and Elliot C.
10.Du Bois RM, Weycker D, Albera C, et al. Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med. 2011;184(12):1382-9. doi:10.1164/rccm.201105-0840OC
11.United States National Library of Medicine website.“Idiopathic Pulmonary Fibrosis http://ghr.nlm.nih.gov/condition/idiopathic-pulmonary-fibrosis. Accessed October 7, 2014
12.Raghu G et al. Am J Respir Crit Care Med 2011;183 :788−824
13.National Institutes for Health website. “Idiopathic Pulmonary Fibrosis” http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/. Accessed October 2, 2014

SOURCE: Roche