FRIMLEY, England, May 27 /PRNewswire/ --

- RECORD-1 trial shows RAD001 reduces risk of disease progression by 70%(1) - Exceptional interim results caused independent data monitoring committee to immediately share findings; patients on placebo offered RAD001(2) - RAD001 is first and only drug to date to show significant benefit after failure of approved therapies Sutent(R) (sunitinib), or Nexavar(R) (sorafenib),** with potential to address unmet medical need(1) - Once-daily oral RAD001 directly targets and continuously inhibits mTOR, a protein that controls tumour cell division and blood vessel growth(1)

New data show RAD001 (everolimus) may provide an important new treatment option for patients with advanced kidney cancer who have failed standard therapies.

The interim study findings demonstrated that RAD001, an investigational drug being studied in multiple tumour types, significantly extended the time without tumour growth from 1.9 to 4 months and reduced the risk of cancer progression by 70% (hazard ratio = 0.30 with 95% CI 0.22 to 0.40; p-value < 0.0001).(1) The study, RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily), will be presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois, US on Saturday, 31 May, 2008.

"These findings provide important information on the efficacy of RAD001, the first and only drug to date that has demonstrated clinical benefit in advanced kidney cancer patients who have experienced treatment failure with the most commonly used first-line therapies," said Dr Peter Harper, Consultant Medical Oncologist, Guy's and St Thomas'. "I am encouraged by these results and of the potential of RAD001 to address an unmet medical need for this population of very ill patients."

Earlier this year, an independent data monitoring committee stopped the RECORD-1 trial after interim results showed that patients receiving RAD001 experienced a significantly longer time without their cancer worsening compared to patients receiving placebo. The trial included patients whose cancer had stopped responding to approved treatments for renal cell carcinoma (RCC), such as Nexavar(R) or Sutent(R), or both.(1)

RAD001 is a once-daily oral therapy that may offer a new approach to cancer treatment by continuously inhibiting the mTOR protein, a central regulator of tumour cell division and blood vessel growth in cancer cells. RAD001 is currently being studied in multiple types of cancer including neuroendocrine, breast, gastric, lung, and lymphoma.(2)

"Every year there are about 6,000 newly diagnosed cases of kidney cancer in the UK -- that's 16 new cases per day or one every 90 minutes -- and the incidence is steadily increasing," said Pat Hanlon, Kidney Cancer UK. "Advanced kidney cancer is especially difficult to treat effectively; we are therefore excited by the results from the RECORD-1 study, which offer hope to this group of very ill people who have few other treatment options available to them."

During the second half of 2008, the interim results from RECORD-1 will be used to submit a new drug application for RAD001 as a treatment for metastatic RCC.


1. Novartis data on file

2. Novartis press release (28 Feb 2008)

3. Novartis data on file

4. McLaughlin JK, Lipworth L, Tarone RE. Epidemiological aspects of renal cell carcinoma. Semin Oncol. 2006 Oct;33(5):527-33. [Abstract]

5. American Cancer Society .asp Last accessed 21.05.08

Notes to editors

About renal cell carcinoma (RCC)

Renal cell cancer accounts for 2% of all new cancer cases worldwide with occurrence rates rising steadily around the world.(4) In the UK, RCC has increased by 22% over the last ten years. Each year, approximately 6,600 people in the UK are diagnosed with kidney cancer, which also causes around 3,600 deaths each year.(3) There are several types of RCC, but the most common, called clear cell, accounts for 80% of diagnoses.(5) In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumour.

About RAD001

RAD001, an oral inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. In cancer cells, RAD001 inhibits mTOR, a protein that acts as a central regulator of tumour cell division, cell metabolism, and blood vessel growth. RAD001 is a once-daily oral therapy that provides continuous inhibition of mTOR.(3)

In addition to RCC, RAD001 is presently being evaluated in neuroendocrine tumours, lymphoma, other cancers, and tuberous sclerosis as a single agent or in combination with existing cancer therapies.(2)

As an investigational compound, the safety and efficacy profile of RAD001 has not yet been established in oncology. Access to RAD001 is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that RAD001 will ever be commercially available for oncology indications anywhere in the world. Everolimus is approved under the trade-name Certican(R) for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003 and is available in more than 60 countries.

RECORD-1 results

RECORD-1 is the largest Phase III clinical trial investigating the effects of an oral mTOR inhibitor in metastatic RCC. It is a randomised, double-blind placebo-controlled multicentre trial of more than 400 patients with RCC whose cancer worsened despite prior treatment, including Nexavar or Sutent, or both.(1) In addition, prior therapy with Avastin, interferon, and interleukin-2 was allowed. (1)

The primary endpoint of RECORD-1 was progression-free survival (PFS) assessed via a blinded, independent central review and defined as the amount of time between randomisation and first documented disease progression or death due to any cause.(1) Results of the study demonstrated a statistically significant improvement in PFS for RAD001 compared to placebo (hazard ratio = 0.30 with 95% CI 0.22 to 0.40; p-value < 0.0001; median PFS 4 months vs. 1.9 months, respectively). (1)

Secondary endpoints included comparison of overall survival, objective response rate, quality of life, safety, and pharmacokinetics. There was no significant difference in overall survival between the RAD001 and placebo groups (hazard ratio = 0.83 with 95% CI 0.50 to 1.37; p-value = 0.23).(1) The study design allowed patients to be unblinded at the time of radiological disease progression; patients receiving placebo were allowed to cross over to receive RAD001.(2) There was no significant difference in objective response rate between the RAD001 and placebo groups (1% vs. 0% of responders). However, in a central review among patients evaluable for best percentage change in target lesions (223 and 107 in RAD001 and placebo arms, respectively), tumour shrinkage was observed in 50% of patients receiving RAD001 during the double-blind portion of the study versus 8% of patients receiving placebo. (1) Quality of life measurements taken throughout the study showed no significant difference between the RAD001 and placebo groups.(1)

Safety findings in the study were consistent with those seen in prior Phase II studies. The most frequent adverse events in patients who took RAD001 included mouth sores (40%), feelings of weakness (37%), and rash (25%). There was a low incidence of grade 3 or 4 drug-related adverse events (> 1% of patients listed): mouth sores (3%), lung inflammation (3%), infection (3%), tiredness/feelings of weakness (4%), diarrhoea (1%), mucosal inflammation (1%), and difficulty breathing (1%). The trial had a low rate of adverse drug reactions leading to discontinuation among patients who took RAD001 (6%).(1)

About Novartis

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world. For more information, please visit

**Sutent is a registered trademark of Pfizer Inc. Nexavar is a registered trademark of Bayer HealthCare Pharmaceuticals, Inc.

For more information, please contact: Fiona Turner, Novartis Pharmaceuticals UK Ltd, Tel: +44(0)1276-698086, Fax: +44(0)1276-698605, Email:; Charlotte Binstead, Red Health, Tel: +44(0)207-025-6592, Fax: +44(0)207-025-6499, Email: