New Viracept: same efficacy with 4 rather than 10 pills and less gastrointestinal side effects

Basel, 7 May 2003 � Roche Pharmaceuticals today filed its submission to the European Authorities for its long awaited new 625mg formulation of top selling HIV protease inhibitor Viracept^� (nelfinavir).  When approved, the new formulation will reduce Viracept's pill count from 10 to four tablets per day compared to the current 250mg tablet, offering patients a much simpler dosing regimen with the same level of efficacy. Moreover, it will offer a marked reduction in the occurrence of diarrhoea � one of the most common side effects associated with protease inhibitors.

Study results^1,2,3 showed that patients being treated with Viracept 250mg* saw a noticeable, clinical improvement in gastro-intestinal (GI) tolerability when they switched to the 625mg formulation (8.1% of patients being treated with the 250mg tablet experienced moderate or severe diarrhoea compared to 1.6% when those patients switched to the 625mg formulation). Final results are expected in July at the International AIDS Society�s 2^nd Conference on Pathogenesis and Treatment.

�Viracept has been an important first line therapy in HIV treatment for several years now.�  comments Dr Santiago Marco Ibanez, International Medical Manager, Roche Pharmaceuticals.  �Soon we hope to be able to offer patients and treating physicians the same safety, efficacy and unique resistance profile they have always had with Viracept, but with under half the number of pills each day and less gastrointestinal upset. We hope that the improved convenience and tolerability of the new Viracept formulation will strengthen its use as first line therapy allowing prescribers to later on use further PI options.�

An approval is expected in mid 2004. Filing in additional countries will follow shortly.

 For more information please contact:

Daniel Kent	Santiago Marco Ibanez
Ketchum, London	Roche, Basel
Telephone:  + 44 207 611 3677	Telephone: +41 61 68 82091
E-Mail: daniel.kent@ketchum.com	Email: Santiago.marco_ibanez@roche.com

Editor�s Note: Study Details

An interim analysis of this multi-centre, international exploratory study was presented on 82 randomised patients; 62 patients switching from the existing 250 mg tablets and 20 �new� patients initiating Viracept. All patients were given 1250 mg twice daily of the existing 250mg tablets for two weeks followed by 4 weeks with the new 625mg formulation.  Interim results from patient diary data demonstrated that in switch patients diarrhoea was absent in 45/61 (74%) patients while on the 625mg formulation compared with 30/62 (48%) patients receiving the 250mg formulation. In accordance with normal clinical practice, the use of anti-diarrhoeal medication was not prohibited. However, only 11/62 and 3/20 patients (switch and new arm respectively) chose to take antidiarrhoeal medication (loperamide and calcium carbonate) at any point during the study period.

Similar results were seen in one other study exploring the GI side effects of the two Viracept formulations in healthy volunteers³. Bioequivalence (equivalent rate and extent of absorption in the body) was confirmed between the Roche 625 mg tablet and the commercial 250 mg tablet at the dose of 1250 mg recommended for the twice-daily regimen.²

Viracept-based highly active antiretroviral therapy (HAART) has been clinically proven to provide potent and durable suppression of HIV replication over at least 4 years of continuous treatment.⁴ In addition, viracept-based therapy has shown comparable efficacy to novel agents such as atazanavir,⁵ abacavir⁶ and boosted fosamprenavir (GW433908)⁷ in large, randomized clinical trials.

Viracept allows the future use of boosted protease inhibitors (PIs) through its unique resistance profile,⁸ and has excellent tolerability and safety profiles that are characterized by low rates of toxicity-related therapy discontinuations and a lack of major organ toxicities.⁴

Under the current co-licensing agreement Roche�s 625mg formulation of Viracept will be manufactured and marketed in all countries except the US and Canada.  For information on Viracept 625mg in the US and Canada please contact Agouron Pharmaceuticals.

* Interim analysis on 82/188 with a switch/new ratio of 62/20.

References:

1. L. Nieto-Cisneros, M. Johnson, A. Horban, K. Arasteh, J. Gonzalez-Garcia, S. Proll, R. Foreman and P. Smith.  Investigation of the gastrointestinal tolerability and pharmacokinetics of the Roche nelfinavir 625 mg film-coated tablets in comparison with nelfinavir 250 mg film-coated tablets (Viracept^�) in HIV patients. 4^th International Workshop on     Clinical Pharmacology of HIV Therapy. Cannes, France, March 2003; Poster Number: 6.6.

2. J.-E. Charoin, P. Oxley, M. Gerber, N. Saiedabadi, B. Kaeser.  Pharmacokinetics of Roche nelfinavir 625 mg film-coated tablets and nelfinavir 250 mg film-coated tablets (Viracept^�) are bioequivalent. 4^th International Workshop on Clinical Pharmacology of HIV Therapy. Cannes, France, March 2003; Poster Number: 6.5.

3. B Kaeser, D-J Akintola, A Saifulanwar, M Boyce, P Smith. Improved gastrointestinal (GI) tolerability of Roche nelfinavir 625 mg film-coated tablets in comparison with nelfinavir 250 mg film-coated tablets (Viracept^�). 4^th International Workshop on Clinical Pharmacology of HIV Therapy. Cannes, France, March 2003; Poster 6.4.

4. Gathe et al. 8^th European Conference on Clinical Aspects and Therapy of HIV Infection. Athens, Greece, 2001; poster LB/P10.

5. Sanne et al. 41^st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, USA, 2001; abstract I-667.

6. Matheron et al. XIII International AIDS Conference. Durban, South Africa, 2000; abstract WeOrB605.

7. Sch�rmann et al. 6^th International Congress on Drug Therapy in HIV Infection. Glasgow, UK, 2002; poster PL14.4.

8. Tebas P, Patrick A, Kane EM et al. AIDS 1999; 13:F23-F28

Viracept 625mg data

In addition to the GI study in HIV patients two additional studies were presented at the International Workshop on Clinical Pharmacology on HIV Therapy:

1. Results of the pharmacokinetics trial confirmed bioequivalence of new 625mg formulation with commercial 250mg tablet at a single dose of 1250mg after administration in fed state.

 2. Results of GI tolerability trial in healthy volunteers comparing tolerability of new 625mg formulation with nelfinavir 250 mg found no incidences of moderate or severe diarrhoea with either treatment.

Roche in HIV

Roche is at the forefront of efforts to combat HIV infection and AIDS, committed since 1986 to groundbreaking research and development of innovative new drugs and diagnostic technology. Saquinavir was the first Protease Inhibitor (PI) and was first introduced by Roche in 1995 in the US.

As a consequence of Roche's continuous research and development, the combination of boosted saquinavir with ritonavir (1000/100 mg twice daily) has shown encouraging results in the MaxCmin 1 trial with high efficacy and an excellent safety and tolerability profile. Saquinavir/r was approved in the EU in August 2002. Viracept (nelfinavir), a leading  PI is supplied by Roche outside the US and Canada. In first-line HIV therapy, Viracept delivers consistent long-term efficacy and safety. When used first line, Viracept also allows the subsequent use of both NNRTIs and other PIs for most patients due to its unique resistance pattern. Fuzeon and T-1249 are being co-developed by Roche and Trimeris.

The viral load measurements in the clinical trials for Fuzeon were performed using the AMPLICOR HIV-1 MONITOR version 1.5 assay. This test from Roche Diagnostics is considered to be a highly sensitive measurement of the amount of HIV circulating in a patient�s blood (�viral load�). With a limited number of treatment regimens available, the accurate monitoring of viral load levels is essential to establish and monitor the effectiveness of therapeutic regimens and assess the potential onset of drug resistance.

Roche is a committed partner of the Accelerating Access Initiative to increase access to HIV care in sub-Saharan Africa and the world's Least Developed Countries. For more information on Roche policy and pricing of HIV protease inhibitors for these regions and research in HIV, visit www.roche-hiv.com.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world�s leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people�s health and quality of life. Roche employs roughly 62,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.

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