Investor Update

Basel, 27 August 2013

Roche’s lampalizumab phase II data shows benefit in patients with the advanced form of dry age-related macular degeneration

Phase II data met its primary efficacy endpoint in slowing the progression of geographic atrophy lesions in patients with advanced dry age-related macular degeneration

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced positive phase II results from the MAHALO study demonstrating that lampalizumab (also referred to as anti-factor D) showed a 20.4 percent reduction rate in the area of geographic atrophy at 18 months in patients with this advanced form of dry age-related macular degeneration (AMD). The MAHALO phase II data also showed no unexpected or unmanageable serious adverse events associated with lampalizumab. These data were presented at the 31st Annual Meeting of the American Society of Retina Specialists in Toronto, Ontario, Canada.

AMD is a leading cause of blindness in adults over 55 years of age in the developed world. There are two forms of AMD, neovascular or wet AMD and dry AMD. Geographic atrophy is the advanced form of dry AMD and is characterised by the irreversible loss of retinal tissue in the macula that results in permanent blind spots in a patient’s central vision.

Geographic atrophy (GA) affects more than 8 million people worldwide.1 While therapies have become available for wet AMD, currently there are no approved treatments for people with GA. MAHALO is the first study to show a beneficial treatment effect with a complement inhibitor in geographic atrophy. Efficacy of lampalizumab was observed in the monthly group beginning at month six and was maintained through month 18.

“The phase II results are encouraging for patients with geographic atrophy, a major vision-impairing disease where there is a great need for treatment options,” said Richard Scheller, Ph.D., Head of Genentech Research and Early Development. “We are continuing to investigate our emerging biomarker strategy to identify people who would be appropriate candidates for treatment with lampalizumab.”

In a specific sub-population of GA patients treated monthly with lampalizumab that were identified using exploratory biomarkers, the GA progression rate was decreased by 44 percent (p<0.005) at 18 months. In the subset of patients positive for the exploratory biomarkers who presented with better vision (20/50 to 20/100), progression of the GA area was reduced by 54 percent (p<0.005) at 18 months when treated with monthly lampalizumab. From the patient samples collected in the MAHALO study, 57 percent of patients were positive for the exploratory biomarkers. More information on the biomarkers will be shared at a future medical congress.

About the MAHALO study

The phase II trial was a multi-centre, randomised, single-masked, controlled study of the safety, tolerability and evidence of activity of lampalizumab in patients with GA associated with AMD. Study participants received lampalizumab injections in one eye either monthly or every other month for 18 months. The primary endpoint was change of GA area from baseline to month 18 compared with control, as assessed with fundus autofluorescence (FAF). Lampalizumab showed a 20.4 percent reduction rate in the area of geographic atrophy at 18 months (p<0.1170, statistically significant per pre-specified protocol criteria) in patients with this advanced form of dry AMD. The efficacy assessed by FAF was observed in those receiving monthly injections beginning at month six and maintained through month 18. There was no apparent treatment effect observed in the all-comer every other month dosing group. A secondary endpoint of change in GA area from baseline to month 18 was assessed by colour fundus photographs and confirmed the FAF primary outcome results.   

Safety outcome measures included incidence and severity of ocular and non-ocular (systemic) adverse events (AE). Intraocular inflammation AE rates and intraocular pressure elevation AE rates were consistent with Lucentis rates for these AEs in wet AMD. The most frequently reported AEs in the study eye were associated with the injection procedure. There were no intraocular infections, no unexpected or unmanageable serious AEs, no death or ocular serious AEs suspected to be caused by study drug and no ocular serious AEs in study eye leading to treatment discontinuation.

About lampalizumab

Lampalizumab is being investigated to determine its effect on the progression of GA associated with advanced dry AMD. The molecule is an antigen-binding fragment (Fab) of a humanised, monoclonal antibody directed against complement factor D. Complement factor D is a rate-limiting enzyme involved in the activation of the alternative complement pathway (ACP). The ACP is a component of the immune system's natural defence against infections. Genetic polymorphisms as well as hyperactivity of the ACP have been implicated in the development of AMD including GA.

About geographic atrophy (GA)

GA is an advanced form of AMD and is a progressive, irreversible and blinding disease. GA is responsible for irreversible severe vision loss in approximately 20 percent of all patients with AMD.2-3 Visual impairment associated with GA tends to affect both eyes in many individuals. GA patients report visual problems with reading, recognising faces, and activities in low illumination. GA represents a significant unmet medical need as there are no approved treatments for this condition.

About Roche in ophthalmology

Roche’s ophthalmology medicines include Lucentis (ranibizumab injection), which is indicated in the United States for the treatment of wet age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion (RVO) and diabetic macular edema (DME).

Lucentis was discovered by Genentech and continues to be developed by Genentech and Novartis for diseases or disorders of the eye. Genentech retains commercial rights in the U.S. and Novartis has exclusive commercial rights for the rest of the world.

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, infectious diseases, ophthalmology, inflammation, metabolism 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 diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2012 Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 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.Rudnicka, A. et al,"Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis,"Ophthalmology, 2012; 119:571–580.
2.Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL III; Age-Related Eye Disease Study Research Group. Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS) AREDS report no. 19. Ophthalmology 2005;112:533–9.
3.Zarbin MA, Rosenfeld PJ. Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives. Retina 2010;30:1350–67.