US approval for darunavir (TMC-114, Prezista)

On 23 June 2006, the Food and Drug Administration (FDA), granted accelerated approval in the U.S. for darunavir (formerly TMC-114, tradename Prezista), for treatment experienced adults who are not responding to treatment with other antiretroviral drugs.

Darunavir is a protease inhibitor and needs to be boosted with a low-dose of ritonavir to increase plasma concentrations. The recommended oral dose of darunavir tablets is 600 mg (two 300 mg tablets) twice daily taken with ritonavir 100 mg twice daily.

Darunavir/r needs to be taken with food, although the type of food does not affect exposure to darunavir.

The accelerated approval is based on two randomised, controlled studies comparing the safety and effectiveness of a darunavir/r combination with other ritonavir-boosted protease inhibitor combinations. Patients in both arms of these trials also used other anti-HIV drugs, with or without T-20 (enfuvirtide).

Seventy percent of treatment-experienced patients achieved a virologic response with darunavir/r in combination therapy compared to 21 percent in comparitor-PI control group at week 24.

The most common side effects reported by patients on the darunavir/r regimen included diarrhea, nausea, and headache. About seven percent of patients on this combination therapy experienced skin rashes ranging from mild to serious.

The risks and benefits of darunavir have not been established for treatment naive adults or for children.

Darunavir is manufactured for Tibotec, and distributed by Janssen Cilag, part of the Johnson & Johnson group.

Comment

The UK currently has a named-patient programme for patients requiring darunavir prior to European approval.

The average wholesale price announced for darunavir in the US was $25.00 a day (excluding cost of boosting ritonavir, and other ARVS used in the combination), which is very close to atazanavir.

In the weeks prior to approval a wide networks of community advocates and organisations in the US petitioned Tibotec over pricing of darunavir. Historically, it has been the rule, rather than the exception (ie probably all ARVs except indinavir and nevirapine) for companies to price new compounds significantly higher than existing antiretrovirals.

The prices of the last two protease inhibitors, atazanavir (Reyataz) from Bristol Myers Squibb and tipranavir (Aptivus) from Boeringher Ingelheim, each in turn set new record high prices for drugs in their class, bringing the US price of protease inhibitors alone to well over $10,000 and the cost of a typical regimen in excess of $16.000.

While the cost of treatment at the current levels is prohibitive for many, and burdens US assistance programmes like ADAP, where many states already have waiting lists for ARV therapy, the response from some activist groups recognised the positive effect from pricing darunavir at the same level as atazanavir. Reading between the lines – it could have been worse.

AIDS Treatment News commented that the lower price could well be in the companys financial interest, by allowing first-line use if the drug proves suitable – especially important now that its rival tipranavir does not seem to be working well as a first-line treatment, because of performance that appears slightly inferior to a good standard treatment based on Kaletra and that there is much hope for darunavir as first-line therapy, but we do not have the data yet.