New Treatment Significantly Improves Vision in Patients With Wet Age-Related Macular Degeneration - The Leading Cause of Blindness in the UK

FRIMLEY, England, October 5 /PRNewswire/ --

Data published today in the New England Journal of Medicine (NEJM) show that ranibizumab (Lucentis(R)), a potential new treatment for patients with wet AMD, is the first treatment to significantly improve vision[1] in large scale (phase III) clinical trials.

The data from MARINA, one of two pivotal studies show that ranibizumab prevented visual loss or actually improved[x] vision in 9 out of 10 patients with some forms[xx] of wet AMD versus 5 of 10 patients in the untreated group after 2 years (P<0.001). Furthermore, over a third of patients treated with the 0.5mg ranibizumab dose experienced a marked visual improvement of at least 15 letters or more versus only 4% in patients who were untreated (p<0.001).

Mr Yit Yang, Consultant Ophthalmologist from Wolverhampton said: "These results are very striking. With ranibizumab we will have the opportunity, at least in cases treated without delay, of reversing the visual loss and maintaining the improved vision for up to two years or longer. This is undoubtedly an important breakthrough for this condition and we are looking forward to being able to use this treatment once it is licensed."

Mr Yang added: "These results mean that potentially people with wet AMD can become independent again and return to activities such as reading, shopping and hobbies that they may have been forced to give up due to central vision loss caused by wet AMD.

Mr Steve Winyard, Director of Public Policy at RNIB said: "Although this is not a cure, ranibizumab is great news for individual patients, as it offers them the chance of having their vision restored. In addition, on a national level it raises the prospect of being able to significantly reduce the number of people being registered legally blind due to wet AMD. This would enable government to take a significant step forward on its Vision 2020[2] commitment to reduce avoidable sight loss."

Mr Winfried Amoaku, Consultant Ophthalmologist in Nottingham said: "Current treatments are very useful in that they allow us to preserve the level of vision that patients currently have, but Ranibizumab is the first therapy that could allow us to significantly improve patients' sight. We are looking forward to the availability of ranibizumab on the NHS once it receives its license so that wet AMD patients in the UK are able to receive the widest possible choices of treatments."

Steve Winyard added: "It is crucial that people have a regular eye test. In addition anyone who notices a change in their vision should go immediately to see their optician. The earlier wet AMD is diagnosed the better allowing prompt referral to a retinal specialist to potentially reduce the risk of severe vision loss.[3]"

The full results of the 2-year MARINA study and the first year results of the 2-year ANCHOR trial published in today's NEJM demonstrate that ranibizumab is effective and well tolerated. Ranibizumab has been submitted for European Union approval and is expected to be available in the UK at the end of 2006 / beginning of 2007.

Novartis is committed to ophthalmology and our mission is to discover and develop innovative products to improve eye health and enhance people's lives.

Notes for Editors:

More than 9 out of 10 ranibizumab treated patients avoided visual loss over 2 years versus approximately 52% of patients in the untreated group (P<0.001).

MARINA findings

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 who were randomized 1:1:1 to receive 0.3 mg of ranibizumab, 0.5 mg of ranibizumab or a placebo control - approximately 240 patients per study arm. The one- and two-year MARINA results demonstrate the following:

- One-year:

- 95 percent of patients receiving 0.3 mg ranibizumab and 0.5 mg ranibizumab lost fewer than 15 letters in visual acuity from baseline versus 62 percent of patients in the placebo controlled group. Visual acuity was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart.

- 25 percent of patients receiving 0.3 mg ranibizumab and 34 percent of patients receiving 0.5 mg ranibizumab had a gain of 15 letters or more in visual acuity compared to 5 percent of patients in the placebo controlled group.

- Ranibizumab -treated patients, on average, experienced an increase of 6.5 letters (0.3 mg) and 7.2 letters (0.5 mg) in mean visual acuity. Patients in the placebo controlled group, on average, lost 10.4 letters in mean visual acuity.

- Two-year:

- 92 percent of patients receiving 0.3 mg ranibizumab and 90 percent of patients receiving 0.5 mg ranibizumab lost fewer than 15 letters in visual acuity from baseline versus 53 percent of patients in the placebo controlled group.

- 26 percent of patients receiving 0.3 mg ranibizumab and 33 percent of patients receiving 0.5 mg ranibizumab had a gain of 15 letters or more in visual acuity compared to 4 percent of patients in the placebo controlled group.

- Ranibizumab -treated patients, on average, experienced an increase of 5.4 letters (0.3 mg) and 6.6 letters (0.5 mg) in mean visual acuity. Patients in the placebo controlled group, on average, lost 14.9 letters in mean visual acuity.

Adverse effects were similar to those seen in earlier trials of ranibizumab. Serious ocular adverse events occurring more frequently in ranibizumab treated patients were uncommon (<=1.3%) and included uveitis and endophthalmitis. There appeared to be no imbalance in serious non-occular adverse events.

ANCHOR findings

ANti-VEGF Antibody for the Treatment of Predominantly Classic CHORoidal Neovascularisation in AMD (ANCHOR) is a Phase III, multi-center, randomized, double-blinded, active treatment-controlled study of ranibizumab administered as a monthly intravitreal injection compared with photodynamic therapy (PDT) administered according to label.

ANCHOR enrolled 423 patients in the United States, Australia and Europe who were randomized 1:1:1 to receive 0.3 mg of ranibizumab, 0.5 mg of ranibizumab or PDT - approximately 140 patients per study arm.

- One-year:

- 94 percent of patients receiving 0.3 mg ranibizumab and 96 percent of patients receiving 0.5 mg ranibizumab lost fewer than 15 letters in visual acuity from baseline versus 65 percent of patients receiving PDT. Visual acuity was measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart.

- 36 percent of patients receiving 0.3 mg ranibizumab and 40 percent of patients receiving 0.5 mg ranibizumab had a gain of 15 letters or more in visual acuity compared 6 percent of patients receiving PDT.

- Ranibizumab-treated patients, on average, experienced an increase of 8.5 letters (0.3 mg) and 11.3 letters (0.5 mg) in mean visual acuity. Patients receiving PDT, on average, lost 9.5 letters in mean visual acuity.

Two year ANCHOR data is expected in fourth quarter 2006.

Preliminary safety findings were consistent with those observed in the other Phase III pivotal study of ranibizumab, MARINA. Serious ocular adverse events that occurred more frequently in the ranibizumab-treated arms were uncommon and included endophalmitis (1.3% ). Among non-ocular and serious ocular events, the frequency of cerebral vascular events were equal across all three arms. The frequency of myocardial infarctions was slightly higher in patients treated with 0.5mg (3/140) of ranibizumab than in the other two arms

About Ranibizumab

Ranibizumab is an anti-VEGF (anti-Vascular endothelial growth factor) therapy, designed to treat the underlying cause of wet AMD. VEGF is a protein that is thought to play a critical role in the formation, growth and leakage of abnormal blood vessels (angiogenesis) which leak fluid and blood causing distorted central vision that occurs in the eye in wet AMD[4]. Anti-VEGF therapies bind to VEGF with the aim of blocking its effect to try and prevent more blood vessels from growing.[5]

About Novartis

Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2004, the Group's business achieved sales of USD 28.2 billion and a 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. For further information please consult http:/www.novartis.com

About AMD

- AMD (Age-related Macular Degeneration) is the leading cause of blindness in the UK affecting approximately 417,000 people[6] and accounts for more than half of registered blindness in the UK[7]

- AMD affects the macular - the central part of the retina at the back of the eye that is responsible for the 'straight-ahead' vision necessary for everyday activities, like reading, driving, telling the time or identifying faces central vision.[8] AMD also takes away a person's independence and confidence, and can lead to depression.[9]

- There are two types of AMD, dry and wet.[8] Although wet AMD is the minority form of the disease it is very aggressive and accounts for 90% of blindness caused by this condition.[8] Wet AMD is associated with the growth of new blood vessels in the macula (angiogenesis). These vessels are fragile and leak fluid and blood, leading to the development of scar tissue that destroys the macula.[8]

[x] In clinical trials improvement of vision is defined as a gain of 0 letters or more in visual acuity as measured on an Early Treatment of Diabetic Retinopathy (ETRDS) chart, the standard method of quantifying visual acuity. Visual acuity refers to the ability of patients to detect fine detail or small distances with the eye.

[xx] Minimally Classic and Occult no Classic wet AMD

[1] Ranabizumab for Neovascular Agre-related Macular Degeneration Rosenfeld et al N ENGL J MED 355:14, Oct 2006

and Ranabizumab versus Verteporfin for Neovascular Agre-related Macular Degeneration Brown D. M. et al N ENGL J MED355:14, Oct 2006

[2] National eye care services steering group: first report

[3] Sickenberg M. Early Detection, Diagnosis and management of Choroidal Neovascularisation in Age-Related Macular Degeneration: The Role of Ophthalmologists. Ophthalmologica. 2001;215:247-253.

[4] Witmer AN et al. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 2003; 22: 1-39

[5] Ferrara N, Gerber HP, Jennifer Couter J. The biology of VEGF and its receptors. Nature Medicine 2003; 9: 669-676.

[6] Owen C G, Fletcher A E, Donoghue M et al. How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom? Br J Ophthalmol. 2003; 87: 312-317.

[7] Evans J, Wormald R. Is the incidence of registerable blindness age-related macular degeneration increasing? Br J Ophthalmol. 1996; 80: 9-14.

[8] Bressler NM. Early detection and treatment of Neovascular age-related macular degeneration. JABF. 2002; 15:2.

[9] Brody L, Gamst AC, Williams RA et al. Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration. Ophthalmology 2001;108:1893-1901.