Novartis announced today additional positive one-year data from two key clinical studies, MARINA and FOCUS, of the investigational new drug Lucentis (ranibizumab). Both studies successfully reached their primary endpoints and reported unprecedented results in maintaining and/or improving vision for patients with wet age-related macular degeneration (AMD). The trial results were presented today at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS) in Montreal, Canada.

"We are delighted that these results show an improvement in vision, which is a significant breakthrough for AMD therapy and an important clinical outcome for physicians and the patients who suffer from this devastating disease," said Flemming urnskov, M.D., President, Novartis Ophthalmics Business Unit.

Data from MARINA, a Phase III clinical study of 716 patients with minimally classic or occult wet AMD, show that, at 12 months, approximately 95 percent of patients treated with Lucentis maintained or improved vision (defined as a loss of less than 15 letters in visual acuity on the Early Treatment of Diabetic Retinopathy (ETDRS) chart), regardless of whether they received 0.3 mg (94.5 percent, 226/238) or 0.5 mg (94.6 percent, 225/240) of Lucentis, compared with 62.2 percent (148/238) of those in the sham control group (p0.0001). To perform a sham injection, the treating physician prepares and anesthetizes the patient's eye but does not perform the injection.

Vision improved by more than 15 letters in 24.8 percent (59/238) of patients treated with 0.3 mg of Lucentis and 33.8 percent (81/240) of patients treated with 0.5 mg compared to approximately 4.6 percent (11/238) of patients in the control group (p0.0001).

From baseline to month 12, there was a 17 letter difference in mean change in visual acuity between treatment groups. At 12 months, patients treated with Lucentis experienced a mean increase of 7 letters in visual acuity, while patients in the control group experienced a mean decrease of 10.5 letters (p<0.0001).

"These data are very compelling because, for the first time, we have a potential treatment which has been shown to improve vision in a significant number of patients with wet AMD as opposed to just slowing progression of vision loss," said Joan W. Miller, M.D., retina specialist at the Massachusetts Eye and Ear Infirmary who presented the data today.

An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common ocular side effects occurring in the Lucentis arms more frequently than in the control group were mild to moderate and included conjunctival hemorrhage, eye pain and vitreous floaters. Serious ocular adverse events occurring more frequently in patients treated with Lucentis were uncommon (<1%) and included uveitis and endophthalmitis. There was no apparent imbalance in serious non-ocular adverse events.

FOCUS Trial Results

FOCUS, a Phase I/II clinical study investigated the safety and efficacy of Lucentis in combination with verteporfin (Visudyne(R)) photodynamic therapy (PDT) compared to PDT alone in patients with predominantly classic wet AMD.

FOCUS met its primary efficacy endpoint of maintaining or improving vision (defined as a loss of less than 15 letters in visual acuity on ETDRS chart). Results at 12 months showed that over 90 percent of patients (95/105) treated with the combination maintained or improved vision compared to approximately 68 percent (38/56) treated with PDT alone (p0.0003).

An analysis of the one-year data showed there was an increased risk of the ocular adverse event severe uveitis in patients treated with Lucentis in combination with PDT compared to patients treated with PDT alone. An amendment to the study protocol was made after data safety monitoring identified this imbalance. Serious uveitis was more common than previously observed in studies of Lucentis as monotherapy and occurred predominantly following the first dose. On average, patients in this group had a better visual outcome than those treated with PDT alone. After uveitis, endophthalmitis was the second most common ocular serious adverse event occurring in patients treated with Lucentis. Among non-ocular serious adverse events, the frequency of non-fatal cerebral vascular events was higher in those treated with Lucentis and PDT, while the frequency of non-fatal myocardial infarctions was higher in the PDT-alone arm. In both cases, the difference between groups was not statistically significant.

"These preliminary results are important because they further support Lucentis' efficacy. In addition, they show that combining Lucentis with PDT significantly improves visual outcomes," said Dr. Ørnskov.

About the MARINA Study

Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab (formerly, RhuFab) In the treatment of Neovascular AMD (MARINA) is a Phase III study of 716 patients in the United States with minimally classic or occult wet AMD who were randomized 2:1 to receive intravitreal injections of Lucentis or a control treatment (sham injections). Patients treated with Lucentis were further randomized to receive either a 0.3 mg or 0.5 mg dose of Lucentis once a month for two years. Exclusion criteria included prior subfoveal laser treatment, PDT or experimental treatments for wet AMD. Visual acuity was measured using the ETDRS chart, the standard method of quantifying visual acuity.

About the FOCUS Study

The FOCUS (RhuFab V2 Ocular Treatment Combining the Use of Visudyne(R) to Evaluate Safety) trial is a Phase I/II randomized, single-masked study evaluating the safety, tolerability and efficacy of Lucentis in combination with PDT. Conducted at 25 sites in the United States, 162 patients with predominantly classic subfoveal wet AMD were randomized 2:1 to receive PDT followed by either 0.5 mg injections of Lucentis or sham injections for 23 months. All patients received initial treatment with PDT but were only retreated with PDT at the treating physician's discretion based on the Visudyne package insert.

PDT and Lucentis were initially given 7 days apart. The protocol was later amended such that in the remainder of the study, PDT was administered at least 28 days prior to and no sooner than 21 days after administration of Lucentis. The formulation of Lucentis used in this study is different from the one used in monotherapy clinical trials like MARINA and ANCHOR, and will not be commercialized.

Ongoing Phase III Studies

Genentech and Novartis Pharma AG are conducting an additional Phase III study of Lucentis called ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD). This is a randomized, multi-center, double-masked, active treatment controlled study comparing two different doses of Lucentis to PDT in 423 patients. The trial is ongoing in the United States, Europe and Australia with predominantly classic wet AMD. Results from this study are expected in the fourth quarter of 2005.

Genentech is conducting an additional Phase IIIb study, PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or without Classic CNV Secondary to Age-Related Macular Degeneration), a randomized, double-masked, sham injection-controlled study comparing one of two doses of Lucentis to sham injections in 184 patients in the United States with wet AMD. In this trial, Lucentis is administered once per month for the first three doses followed thereafter by doses once every three months for two years. Results from this study are expected in the first half of 2006.

Novartis is committed to further investigating treatment possibilities that can potentially maintain and/or improve vision in patients with wet AMD. Currently, Novartis is conducting the PROTECT study to evaluate the safety of Lucentis administered on the same day as PDT. In contrast to FOCUS, which used the Phase I/II formulation of Lucentis, PROTECT is using the same formulation of Lucentis that is used in the registration trials, MARINA and ANCHOR. Results from the PROTECT study are expected by the end of the year.

About Lucentis

Lucentis (ranibizumab) is a humanized monoclonal antibody fragment designed to bind and inhibit VEGF-A, a protein that plays a critical role in angiogenesis (the formation of new blood vessels).

Consequently Lucentis blocks new blood vessel growth and leakiness which leads to wet AMD disease progression and vision loss. Lucentis is being developed by Genentech and the Novartis Ophthalmics Business Unit. Genentech retains commercial rights for Lucentis in North America (United States, Canada and Mexico). Novartis has exclusive commercialization rights for the rest of the world.

About AMD

AMD is a major cause of painless central visual loss and is the leading cause of blindness for people over the age of 50. It affects over 25 million people worldwide. AMD occurs in two forms: dry and wet. The dry form is associated with atrophy of the central retina or macula, that is required for fine vision used for activities such as reading, driving or recognizing faces. The wet form is caused by growth of abnormal blood vessels also known as choroidal neovascularization (CNV) or ocular angiogenesis under the macula. These vessels leak fluid and blood and cause scar tissue that destroys the macula. These changes result in a deterioration of sight over a period of months to years.

About angiogenesis

Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. In 1989, Napoleone Ferrara, M.D., and a team of scientists at Genentech conducted seminal work in the field, which resulted in the identification and cloning of a gene termed Vascular Endothelial Growth Factor (VEGF), now known as VEGF-A. The VEGF protein plays a critical role in angiogenesis, and serves as one of the key contributors to physiological or pathological conditions that can stimulate the formation of new blood vessels. The process of angiogenesis is normally regulated throughout development and adult life, and the uncontrolled growth of new blood vessels is an important contributor to a number of pathologic conditions, including wet AMD.

The foregoing press release contains certain forward-looking statements that can be identified by terminology such as "investigational"; ", "preliminary", "ongoing", "are expected", "can potentially maintain and/or improve", or similar expressions, or by express or implied discussions regarding potential marketing approvals of Lucentis , or regarding any potential revenues from Lucentis. Such forward-looking statements involve known and unknown risks, uncertainties or other factors that may cause the actual results to be materially different from any future results, performance, or achievements expressed or implied by such statements. There can be no guarantee that Lucentis will be approved for sale in any market or that it will reach any particular sales levels. In particular, management's expectations relating to Lucentis could be affected by, among other things, uncertainties relating to clinical trials; unexpected regulatory actions or delays or government regulation generally; the ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; as well as factors discussed in the Company's Form 20-F filed with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis Ophthalmics

With worldwide headquarters in Basel, Switzerland, the Novartis Ophthalmics Business Unit is a global leader in research, development and manufacturing of leading ophthalmic pharmaceuticals that assist in the treatment of age-related macular degeneration, eye inflammation, glaucoma, ocular allergies and other diseases and disorders of the eye. Novartis Ophthalmics products are available in more than 110 different countries. Novartis Ophthalmics products are made in Switzerland, France, the United States and Canada..

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 83,700 people and operate in over 140 countries around the world.

Source:
John Gilardi
Novartis