The new Roche 625mg formulation of the HIV protease inhibitor Viracept^� (nelfinavir) may offer improved gastro-intestinal (GI) tolerability on top of a simpler dosing regimen compared to the current 250mg dosage regimen.

In addition to reducing pill count from 10 to 4 tablets per day, improvements in GI tolerability have been observed with the new Viracept 625mg formulation, while maintaining equivalent blood levels and hence efficacy.  These results, collated from three clinical studies^1,2,3 are  released for the first time today.  Submission of the Marketing Authorisation Application in the EU for the new formulation is expected in May 2003.

The first ever study in patients using this new formulation¹ was presented today in an interim analysis by Dr Margaret Johnson of the Royal Free Hospital, London. This gives an indication that the new Viracept 625mg formulation may offer patients a clinical improvement in GI tolerability.  Diarrhoea is known to be one of the common side effects usually associated with HIV protease inhibitors.  Patients being treated with Viracept 250mg* saw a noticeable, clinical improvement in 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).

Dr Johnson, a lead investigator in the trial, reports,   �A lot of drugs are offered now at reduced pill count without improvement of their side-effects profile.  It is interesting that the Viracept 625mg formulation may address both these issues, through an improvement in pill count and with less diarrhoea. Since HIV patients take a complicated cocktail of several different drugs on a daily basis, this would markedly improve convenience and quality of life for patients, and may improve adherence.�

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

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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

Nelfinavir-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, nelfinavir-based therapy has shown comparable efficacy to novel agents such as atazanavir,⁵ abacavir⁶ and boosted fosamprenavir (GW433908)⁷ in large, randomized clinical trials.

Nelfinavir 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

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), another 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.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-oriented healthcare groups in the fields of pharmaceuticals and diagnostics.  Roche's innovative products and services address prevention, diagnosis and treatment of diseases, thus enhancing people's well-being and quality of life.

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