HTB South

Cobicistat approved as pharmacokinetic (PK) booster for atazanavir and darunavir in EU prior to the US

Simon Collins, HIV i-Base

On 25 September 2013, Gilead announced that its pharmacokinetic booster cobicistat had been approved in Europe with an indication to boost once-daily use of either atazanavir (300 mg) or darunavir (800 mg), in combination with other ARVs in a combination. [1]

Approval is based on results from a Phase 3 study (study 114) in which cobicistat was non-inferior compared to ritonavir at boosting atazanavir over 48 weeks. All patients also used tenofovir and FTC. Additional PK studies showed cobicistat and ritonavir produce a similar boosting effect on darunavir drug levels.

As with ritonavir, cobicistat has the potential to interact with a wide range of other drugs.

Cobicistat is a selective inhibitor of the cytochrome 450 3A4 liver enzyme responsible for metabolising atazanavir and darunavir which, similar to ritonavir, results in higher drug levels and slower clearance of the boosted drug. Cobicistat is also a CYP3A substrate, a weak CYP2D6 inhibitor and is metabolised, to a minor extent, by CYP2D6. The transporters that cobicistat inhibits include p-glycoprotein (P-gp), BCRP, OATP1B1 and OATP1B3.

Until full prescribing information is available on the EMA website, please see the Gilead press statement for further details. [1]

In Study 114, cobicistat was well tolerated and most adverse events were mild to moderate. The most common adverse reactions (incidence greater than or equal to 10 percent, all grades) were jaundice, ocular icterus and nausea.

Based on the information in the SPC for Stribild, Cobicistat inhibits the tubular secretion of creatinine and may cause modest increases in serum creatinine and modest declines in creatinine clearance (see section 4.8). Patients who experience a confirmed increase in serum creatinine of greater than 26.5 μmol/L (0.3 mg/dL) from baseline should be closely monitored for renal safety.

Cobicistat is dosed at 150 mg once-daily.

Cobicistat is marketed under the brand name Tybost.

References:

  1. Gilead press statement. European Commission approves Gilead Sciences’ Tybost, a new boosting agent for HIV therapy.
    http://www.gilead.com/news/press-releases/2013/9/european-commission-approves-gilead-sciences-tybost-a-new-boosting-agent-for-hiv-therapy
  2. Gilead press statement. Gilead receives complete response letters from U.S. Food and Drug Administration for elvitegravir and cobicistat. (29 April 2013).
    http://www.gilead.com/news/press-releases

Links to other websites are current at date of posting but not maintained.