Investor Update

Basel, 16 November 2013

Roche presents lampalizumab biomarker data from phase II study in advanced form of dry macular degeneration

  • MAHALO phase II data previously showed a reduction in disease progression in patients with geographic atrophy, the advanced form of dry age-related macular degeneration (AMD)
  • Strongest treatment effect was observed in patients positive for the Complement Factor I (CFI) genetic biomarker
  • Roche will continue to investigate the biomarker strategy to identify people who would benefit most from treatment with lampalizumab

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced additional encouraging phase II results with lampalizumab from the MAHALO study in patients with geographic atrophy (GA). GA is characterised by the irreversible loss of retinal tissue in the macula that results in permanent blind spots in a patient’s central vision. In a sub-population of GA patients positive for the Complement Factor I (CFI) biomarker, who received monthly lampalizumab, data from an exploratory analysis show a 44 percent decrease (p<0.005) in the rate of disease progression at 18 months. When lampalizumab was administered every other month, the rate of disease progression was decreased by 18 percent (p=0.23) in the biomarker defined sub-group of patients. No unexpected or unmanageable serious adverse events were detected in the MAHALO study. These data were presented at the 2013 Retina Subspecialty Day Session of the Annual Meeting at the American Academy of Ophthalmology in New Orleans, Louisiana, USA.

“The phase II results are good news for patients with geographic atrophy, a major vision-impairing disease where there is currently no treatment available,” said Richard Scheller, Ph.D., Head of Genentech Research and Early Development. “These preliminary biomarker data show the CFI biomarker could help identify patients most likely to respond to treatment with lampalizumab.”

AMD has a strong genetic component with genetic factors accounting for more than 50 percent of the risk for the disease.1 Genetic polymorphisms in the complement pathway have been implicated in the development of AMD including GA. In the MAHALO study, 57 percent of genotype samples collected from 93 patients were positive for the CFI biomarker. Although the phase II study was relatively small, these results suggest the CFI biomarker is both prognostic for GA area progression and predictive for lampalizumab treatment response. Only MAHALO patients that were positive for the CFI biomarker showed a treatment effect with lampalizumab.

AMD is a leading cause of blindness in adults over 55 years of age in the developed world. There are two forms of AMD, wet AMD and dry AMD. GA, the advanced form of dry AMD, affects more than 8 million people worldwide.2 While therapies have become available for wet AMD, currently there are no approved treatments for people with GA.

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). Four genetic biomarkers were examined in MAHALO, including complement factor H (CFH), C3, C2/CFB and CFI. In the MAHALO study, most patients had a background of CFH and C2/CFB.

Lampalizumab showed a 20.4 percent reduction rate in the area of geographic atrophy at 18 months that was statistically significant (p=0.1170) 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. A secondary endpoint of change in GA area from baseline to month 18 was assessed by colour fundus photographs and these results confirmed the FAF primary endpoint outcome.

In a sub-population of GA patients treated monthly with lampalizumab that were positive for the CFI exploratory biomarker, the GA progression rate was decreased by 44 percent at 18 months (p<0.005).  

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.3-4 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. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age related maculopathy. Am J Ophthalmol 1997; 123: 199-206.
2. 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.
3. 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.
4. Zarbin MA, Rosenfeld PJ. Pathway-based therapies for age-related macular degeneration: an integrated survey of emerging treatment alternatives. Retina 2010;30:1350–67.