Roche Bearer Share : initiates phase III trials for lampalizumab, first potential treatment for geographic atrophy (GA)

Basel, 15 September 2014

• No approved treatment exists for this advanced form of age-related macular degeneration
• The two identical phase III pivotal studies are evaluating potential benefit of lampalizumab on GA lesion progression

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that phase III clinical studies have been initiated for lampalizumab, an investigational drug for geographic atrophy (GA), the advanced form of age-related macular degeneration (AMD), a progressive condition which can result in blindness. The phase III study program will evaluate the safety and efficacy of lampalizumab and its potential to slow the progression of GA. The studies will also further explore if people with a specific genetic biomarker, a mutation in complement factor I, may benefit more from lampalizumab treatment. The trial design was released at the 14th EURETINA Congress 2014 in London.

The MAHALO phase II primary endpoint showed a 20 percent reduction in GA lesion progression in patients treated monthly with lampalizumab as compared with sham at month 18.1 Additionally, data from a sub-population of GA patients receiving monthly lampalizumab and positive for the complement factor I (CFI) biomarker, demonstrated a 44 percent decrease in the rate of disease progression at 18 months.1 This exploratory biomarker analysis will be further evaluated in the phase III program.

"Lampalizumab has the potential to represent a significant breakthrough for this disease and could provide real hope for GA patients," said Sandra Horning, M.D., Head of Global Product Development and Chief Medical Officer at Roche. "It is the first complement targeted therapy for GA to enter phase III, and the only ophthalmic drug in clinical development that specifically targets complement factor D."

The phase III trials, called Chroma (GX29176) and Spectri (GX29185), are identically-designed, double-masked, randomized studies comparing 10 mg dose of lampalizumab administered every 4 or 6 weeks by intravitreal injection to sham injections. Approximately 936 patients will be enrolled in each study (188 biomarker-positive patients and 124 biomarker-negative patients each for the sham, lampalizumab q4w, and lampalizumab q6w treatment groups, in each study). The studies will recruit patients from approximately 300 physician-investigator sites in 24 countries worldwide. Key inclusion criteria are similar to that of the phase II MAHALO study and include the presence of geographic atrophy in both eyes with no history of neovascular (wet) AMD.

The primary objective of the studies is to demonstrate a reduction in the rate of GA disease progression. This efficacy endpoint, evaluated at one year (week 48), is defined as the mean change in the GA lesion area of the chosen study eye from baseline, as measured by fundus autofluorescence (FAF), an imaging technique used to provide information about the size and type of GA lesions in the macula. Secondary objectives of the studies, planned for evaluation at two years (96 weeks), focus on assessing the impact of lampalizumab treatment on patients' visual function. If successful, long-term follow-up of patients completing Chroma and Spectri is planned to continue through a subsequent, open-label extension study.

As analysis of the MAHALO phase II study suggested that the treatment effect with lampalizumab might be stronger in patients positive for the CFI genetic biomarker; therefore, this biomarker will continue to be investigated in phase III.

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).

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 the study drug and no ocular serious AEs in the study eye leading to treatment discontinuation.

Lampalizumab is being investigated to determine its effect on the progression of GA associated with advanced AMD. Lampalizumab 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), a component of the immune system. Genetic polymorphisms as well as hyperactivity of the ACP have been implicated in the development of AMD including GA.

Geographic atrophy is a severe and advanced form of AMD, affecting more than 5 million people worldwide.2 GA is a progressive, irreversible and blinding disease. 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.

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.

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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