Basel, May 23, 2005 - Novartis announced today that a Phase III clinical study of the investigational new drug Lucentis(TM) (ranibizumab) met its primary efficacy endpoint of maintaining vision in patients with wet age-related macular degeneration (AMD).
Approximately 95 percent of patients maintained or improved vision (defined as a loss of less than 15 letters in visual acuity) at one year when treated with Lucentis injections compared to approximately 62 percent of those treated in the control arm (p<0.0001).
Patients treated with Lucentis for 12 months had, on average, a significant improvement in visual acuity compared to their visual acuity at study entry, an important secondary endpoint, while the control group demonstrated a substantial decrease in mean visual acuity from baseline to 12 months. One-year data from the trial will be presented at the 23rd Annual Meeting of the American Society of Retina Specialists (ASRS), July 16 to 20 in Montreal, Canada.
"We are delighted that these results show vision improvement which is an important objective for AMD therapy, and exceeded our expectations. Lucentis will be the first therapeutic antibody which achieves a statistically significant improvement in visual acuity," commented Flemming Ørnskov, M.D., President, the Novartis Ophthalmics Business Unit. "We look forward to sharing these data with the health authorities in due course."
A preliminary analysis of the data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common 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 Lucentis-treated patients were rare (<1%) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-ocular adverse events.
Lucentis is a humanized antibody fragment developed at Genentech and designed to bind and inhibit Vascular Endothelial Growth Factor A (VEGF-A), a protein that plays a critical role in angiogenesis (the formation of new blood vessels).
About the 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 Lucentis injections or a control regimen. The control regimen consisted of a sham injection meaning the treating physician prepares and anesthetizes the patient's eye but does not perform an injection. 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, verteporfin photodynamic therapy, or experimental treatments for wet AMD. Visual acuity was measured using the Early Treatment of Diabetic Retinopathy (ETDRS) chart, the standard method of quantifying visual acuity.
Ongoing phase III studies
Genentech and Novartis are conducting two additional Phase III studies of Lucentis. ANCHOR (ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularization in AMD) is a randomized, multi-center, double-masked, active treatment controlled, Phase III study comparing two different doses of Lucentis to verteporfin photodynamic therapy in 423 patients. The trial is ongoing in the United States, Europe and Australia in patients with predominantly classic wet AMD. Results from this study are expected in Q4 2005.
A Phase IIIb study of 184 patients, PIER (A Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovasularization with or without Classic CNV Secondary to Age-Related Macular Degeneration), is also underway. 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.
About Lucentis
Lucentis (ranibizumab) is a humanized antibody fragment developed at Genentech and designed to bind and inhibit VEGF-A, a protein that plays a critical role in angiogenesis (the formation of new blood vessels). Lucentis is designed to block new blood vessel growth and leakiness, which are thought to lead 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, which 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. This results 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"; "will be", "preliminary", "look forward to"; "ongoing", "are expected", "exceeded", 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. For more information, visit www.novartisophthalmics.com or www.novartisophthalmics.com/us.
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 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world. Further information is available at www.novartis.com.
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