Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Fuzeon (Roche)

vials containing 90 mg/mL as powder for reconstitution

Approved indication: HIV infection

Australian Medicines Handbook section 5.3

Fusion inhibitors are a new class of drugs that prevent HIV from penetrating cells. By binding to an HIV transmembrane glycoprotein they stop the virus from fusing with the CD4 receptors on the patient's cells.

Enfuvirtide is given twice daily by subcutaneous injection. It reaches its peak concentration about four hours after the injection. As enfuvirtide is a peptide it is metabolised into amino acids. It has a half-life of approximately four hours.

Highly active antiretroviral therapy has improved the outlook for patients infected with HIV.1 However, HIV can become resistant to antiviral drugs so that treatment fails to adequately suppress viral replication. Introducing a drug of a new class may help to regain control of the infection.

Clinical trials of enfuvirtide have included patients infected with HIV which had become resistant during at least three months of antiviral treatment. A trial, involving 512 Australian and European patients, randomly added enfuvirtide to an optimised regimen of other drugs for HIV. After 24 weeks the concentrations of viral RNA had fallen further in the patients given enfuvirtide than they had in patients who just took the optimised regimen. There were less than 50 copies of HIV RNA/mL of plasma in 12% of the patients given enfuvirtide compared with 5% of the control group. The CD4 cell count increased in both groups, but the rise was significantly greater in the enfuvirtide group.2

A similar randomised trial in the Americas also found that a regimen containing enfuvirtide had greater efficacy than the same regimen without enfuvirtide. The 328 patients who injected enfuvirtide had greater decreases in viral RNA and greater increases in CD4 count than the 167 patients who took the optimised regimen. After 24 weeks 20% of the enfuvirtide group had less than 50 copies of HIV RNA/mL compared with 7% of the control group.3

Injection site reactions were the commonest adverse reactions to enfuvirtide in the clinical trials. Patients may develop painful itchy nodules at the injection site. Although patients are told to rotate the injection sites they may develop a reaction in more than one place. Approximately 3% of patients withdrew from the trials because of injection site reactions.

In addition to injection site reactions, adverse events tended to be slightly more frequent when enfuvirtide was added to the treatment regimen. Adverse reactions which occurred more frequently with enfuvirtide included peripheral neuropathy, pneumonia and depression. As enfuvirtide is a protein, patients can develop hypersensitivity reactions to its injection. More than 70% of patients treated with enfuvirtide had an adverse event (other than an injection site reaction) resulting in the withdrawal of approximately 8% from the clinical trials.2

The clinical trials are ongoing and preliminary results suggest the effect of enfuvirtide is sustained for 48 weeks. However, the measures of efficacy are surrogate end-points so it will take longer to find out if enfuvirtide improves the clinical outcomes for patients. It is unclear when treatment should be stopped in patients who do not initially respond to enfuvirtide. We also do not know if significant resistance will develop later.

While enfuvirtide is an advance, its use will have to be rationed. There are many steps in the manufacturing process and this may limit the supply of the drug. Until supplies increase enfuvirtide will be an expensive treatment4 (more than $20,000 for a year's treatment).