A new Medicare analysis conducted by Johns Hopkins University presented at the Association for Research in Vision and Ophthalmology (ARVO) meeting represents the largest available dataset comparing the relative safety of unlicensed intravitreal Avastin (bevacizumab) and Lucentis (ranibizumab). These data contribute to the existing body of evidence that suggest that the risk of death and stroke may be higher in patients treated with intravitreal Avastin compared to Lucentis.

"Data presented this week at ARVO underscore the importance of drug design with the patient in mind - aiming for an appropriate balance of efficacy and safety for a given indication and patient population," said Trevor Mundel, MD, global head of development at Novartis Pharma AG. "Now more than ever it is clear that Lucentis and Avastin are different, and Novartis believes Lucentis is the best treatment option for patients with wet AMD."

"Patient safety, informed consent and full disclosure are major priorities for the AMD Alliance International," said Narinder Sharma, chief executive officer, AMD Alliance International. "The Johns Hopkins' data gives us valuable additional information that patients and physicians need to consider and discuss when evaluating anti-VEGF treatment for wet AMD patients."

Novartis believes that unlicensed use of drugs should be limited to cases where there is an unmet medical need which cannot be fulfilled by licensed medications.

The presentation of the large retrospective cohort analysis conducted by Johns Hopkins University follows the announcement of the CATT (Comparison of Age-related macular degeneration Treatment Trials: Lucentis-Avastin Trial) data. Gower et al from Johns Hopkins University is a retrospective database analysis that includes 77,886 Medicare beneficiaries to compare safety of unlicensed intravitreal Avastin compared to Lucentis in patients with wet age-related macular degeneration (AMD).

Over 10 months, patients with wet age-related macular degeneration treated with unlicensed intravitreal Avastin experienced an 11% increased risk of death and a 57% increased risk of hemorrhagic stroke compared to patients treated with Lucentis. There were no statistically significant differences in heart attack and ischemic stroke. The author's noted that the analysis suggest differences in the safety profile of Lucentis and unlicensed intravitreal Avastin, though the study was limited by incomplete information on certain factors such as smoking and blood pressure although adjustment for baseline comorbidities and socioeconmic status was performed.

In the one year results of the CATT, unlicensed intravitreal Avastin administered monthly was non-inferior to Lucentis monthly. Lucentis given 'as needed', which is the treatment regimen registered in the European Union and used by most physicians outside of the United States, was non-inferior to monthly Lucentis. However 'as needed' Avastin failed to meet this endpoint despite a statistically significant higher number of injections. Reductions in retinal thickness and accumulation of fluid in the retina, potential surrogate markers for efficacy, were significantly better with Lucentis, suggesting Lucentis may prove more effective than intravitreal Avastin beyond one year of treatment.

The CATT data also showed numerically more patients on intravitreal Avastin died (Avastin=15, Lucentis=9 at one year) and a significantly higher risk of serious systemic adverse events associated with hospitalizations with unlicensed intravitreal Avastin compared to Lucentis (24.1% vs 19.0%, respectively, p=0.04 ). As highlighted in the recent New England Journal of Medicine report on the CATT results, differences in rates of serious adverse events require further study.

Currently, Lucentis is licensed in more than 85 countries for the treatment of wet age-related macular degeneration (AMD), and in more than 30 countries for the treatment of visual impairment due to diabetic macular edema (DME). In March 2011, Lucentis received a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) for the treatment of visual impairment due to macular edema secondary to retinal vein occlusion (RVO), including both branch- and central-RVO.

Lucentis has a well characterized safety profile and Novartis systematically registers and evaluates the safety and tolerability of Lucentis for licensed indications on an ongoing basis. To date there is more than 750,000 patient-treatment years of exposure globally with Lucentis.

Further, Novartis has launched the Luminous programme, one of the largest observational studies in ophthalmology that will provide additional long-term evidence on Lucentis effectiveness and safety in licensed indications in real-life settings.