Roche's Fuzeon offers hope...to the 20% of patients that receive it

New clinical research presented at the 15th International AIDS Conference (IAC) shows that Fuzeon is proving to be remarkably effective in the first long-term trial of its benefits. Datamonitor's Laura Harris looks at some later line therapies that could be orally available, prompting greater uptake...

Fuzeon (enfuvirtide) was developed by Roche and Trimeris and launched in the US in March 2003, with European launches taking place throughout 2003 and 2004. It was licensed as a salvage therapy in patients who have demonstrated virologic failure to alternative antiretroviral (ARV) treatment and have developed resistant strains of HIV. Fuzeon is the first novel HIV drug to reach the market for a number of years and is the only entry inhibitor currently available.

Further support for Fuzeon

Initial studies demonstrated that the HIV load quickly fell to below detectable levels, with a concomitant increase in the CD4 cell count. Further data presented at IAC showed the drug was found to maintain this strong benefit after 96 weeks of use, without toxic side effects. Indeed, 56% of patients who began the drug were still continuing the treatment after the 96 weeks.

Despite these findings, a second study presented at the IAC found that currently only one out of five eligible patients is receiving Fuzeon as part of their ARV therapy, primarily due to the need to inject the drug. It is common for an adverse reaction to occur at the site of injection and, since two injections every day are required to ensure full efficacy, many patients prefer to take oral ARVs.

"It is alarming that many of these patients offered Fuzeon are not accepting the offer due to the fear of injection and are missing out on the modern era of HIV therapy," commented, Professor Joep Lange, president of the International AIDS Society.

Limited access

Roche and national AIDS organizations are offering education and support programs to help coach patients through the initial stages of Fuzeon therapy (it can be stored at room temperature (59 - 86 degrees Fahrenheit)).

In addition, the considerably high cost of Fuzeon, estimated to be between $15,000-$20,000 per year, has led to many patients being denied access to the drug, particularly in the US where the AIDS Drug Assistance Programs (ADAPs) are becoming increasingly cash-constrained. Correction - Reimbursement for FUZEON has been secured comprehensively across the EU and USA and in particular, in 42 of 50 ADAPs in the USA.

In the face of growing viral resistance to the main classes of ARVs used in first and second line therapy, the novel entry inhibitor class has generated significant interest from the pharmaceutical industry and physician and patient groups alike. Pharmaprojects, a database tracking global R&D pipelines, presented data at IAC showing a rise in the number of anti-HIV drug development strategies being adopted by pharmaceutical companies.

While the most popular ARV drug development strategies remain those that have already proved successful, such as reverse transcriptase inhibition (NRTIs/NNRTIs) and protease inhibitors (PIs), several newer mechanisms of action are now attracting serious attention from the industry. Various methods of entry inhibition, including CC chemokine receptor 5 (CCR5) antagonism, gp120 inhibition and HIV integrase inhibition, are currently being investigated. Recent Datamonitor research found that by 2012, these novel compounds are expected to account for 16% of total HIV market revenue.

In the pipeline

Particular attention is being focused on the orally available and highly active CCR5 inhibitors, with many physicians eagerly awaiting further clinical study results. At this early stage, all had good tolerability and safety profiles although many obstacles lie ahead.

However, the concern that blocking CCR5 co-receptor action may drive evolution of HIV strains towards those which utilize the CXCR4 co-receptor or others appeared to be borne out during the Pfizer trial of UK-427, 857. Strains using CXCR4 are associated with more rapid CD4 decline and disease progression so any selective pressure should be avoided.

Longer term safety studies are still required to establish the true implications of selective pressure and to assess how these drugs might be used or interact with other antiretrovirals. However, should these prove successful, these drugs could enable failing patients to move onto fourth and even later lines of therapy, resulting in high commercial return for the major HIV players, and significant increases in life-expectancy for the HIV/AIDS population.

Related research:

• HIV Resistance: Impact and Evolution
• Pipeline Insight: HIV - Enter the New Generation Inhibitors priced
• Stakeholder Opinions: HIV - Reaching the 'Untapped' Patient Population

To order these reports contact peter.barfoot@bioportfolio.com or telephone +44 1300 321501 or +1 415 680 2472 and a representative will get back to you.

You can also order on line at: http://www.bioportfolio.com/cgi-bin/acatalog/search.html