Named-patient access programme available in UK for new protease inhibitor darunavir (TMC114)

Over the last month named-patient programmes for darunavir (TMC114) have opened in Europe. The drug, produced by Tibotec is currently being reviewed for fast-track approval in the US, based on impressive results in Phase II studies.

The results from the 24-week combined interim analysis of the phase IIB trials of darunavir were presented at the 12th Conference on Retroviruses and Opportunistic Infections (CROI) in February this year and were covered in HTB April 2005. [1]

The study looked at people who had experienced at least 3 classes of antiretrovirals with prior use of at least 1 PI, had at least one primary PI mutation, and viral load >1,000 copies/mL.

Patients were randomised to receive optimal background therapy (OBR, at least 2 NRTIs with or without T-20) and one of 4 doses of darunavir/ritonavir (400/100mg once a day, 800/100mg once a day, 400/100mg BD or 600/100mg BD) or chosen PI (CPI). Based on the 24-week results, the selected dose of darunavir/r for treatment-experienced patients in phase III trials was 600mg/100mg BID.

Baseline median CD4 count and viral load were 141 cells/mm³ and 4.6 log10 copies/mL respectively.

Patients in the highest dose group, 600mg/100mg BID, plus optimised background regimen, experienced a mean reduction in plasma HIV RNA of -1.85 log, compared to a reduction of -0.27 log in the control group.

The 600/100mg twice-daily dosing produced a greater mean change in viral load, a greater percentage of subjects with 1log or more reduction, a marginally greater percentage with fewer than 400 copies/mL, and a greater percentage with fewer that 50 copies/mL than any other group. Mean change in CD4 was +75 cells/mm3 for darunavir/r 600/100 twice-daily vs +15 cells/mm3 for CPI.

Darunavir is being distributed by Janssen-Cilag, a subsiduary of Johnson and Johnson, which in turn is the parent company of Tibotec Therapeutics.

For participation or additional information in the UK please contact the Medical Information Team at Janssen-Cilag on 01494 567444.

Comment

As with every new antiretroviral drug darunavir will only provide limited short-term results if added to an existing failing regimen, or if it is not used in combinations that include other active drugs.

However when darunavir was used with enfuvirtide (T-20), in T-20-naive patients resulted in 63% patients achieving viral suppression <50 copies/mL.

If these results are supported in other studies then this will shift the paradigm for the management of treatment-experienced patients where viral suppression has often been seen as an unrealistic goal. This now show that changing treatment for experenced patients can realistically lead to maximal suppression in the majority of patients, as with other stages of treatment.