Brand name: Not yet established
Generic name: cobicistat, (formerly GS-9350), or COBI
Class: PK enhancer
Manufacturer: Gilead Sciences, www.gilead.com, (800) GILEAD-5 (445-3235)
AWP: TBD; drug not yet approved at press time.
Standard Dose: Not yet established. 150 mg used in research. Cobicistat is not an HIV drug, but is used to increase the levels of elvitegravir (investigational INSTI, see elvitegravir) and HIV protease inhibitors, which will allow for lower and fewer doses of these medications while maintaining their effectiveness. Take missed dose as soon as possible, unless it is closer in time to your next dose. Do not double up on your next dose.
Potential side effects and toxicity: Seen in clinical studies: diarrhea, nausea, lipid elevations (increases in cholesterol and triglycerides), creatine kinase, hematuria (red blood cells in the urine -- urine may look reddish), increased serum creatinine, and decreased estimated glomerular filtration rate (e-GFR) -- the last two are signs of possible kidney malfunction. The increase in serum creatinine is seen within days of initiating cobicistat, but it is reversible and kidney function returns to normal within a few days after stopping cobicistat. The decreased e-GFR appears to not impact health. Available data are limited due to investigational drug status.
Potential drug interactions: Cobicistat is a potent CYP3A4 inhibitor and is likely to increase blood levels of any medications that use this enzyme system to be metabolized. The drug interaction profile will likely not be as extensive as Norvir's because cobicistat only affects CYP3A4, unlike Norvir, which affects other CYP enzymes resulting in more drug interactions. Again, available data are limited due to investigational drug status.
More information: Still in experimental studies, cobicistat is not an HIV medication, but a drug used to boost blood levels of other medications. As such, it is being developed as an alternative to Norvir, an HIV medication used for this same purpose. Specifically, cobicistat and Norvir boost blood levels of HIV protease inhibitors, allowing for fewer pills and (usually) once-daily dosing. Norvir can be difficult to tolerate, has a long list of drug interactions, and its manufacturer angered the HIV community by raising its price 400% one year to make up for its widely used smaller booster dose (initially, it was used in higher doses to fight HIV, like other PIs). Cobicistat is in three advanced Phase 3 trials and Gilead hopes to file the NDA (new drug application) to the FDA during the second quarter of 2012. As an alternative to Norvir, COBI's development has created a lot of excitement. Unfortunately, it has the increased cholesterol and triglycerides of Norvir, along with some of the stomach upsets. There are also concerns about a possible negative impact on the kidneys, although further findings have been reassuring. The 10% increase in creatinine levels that was seen in the first two weeks of study did not continue to increase out to 48 weeks, and was reversible upon stopping cobicistat. Gilead is also creating a single-tablet regimen with COBI in it (see the "Quad" page). Such is COBI's promise that two other HIV drug manufacturers have signed agreements with Gilead to create co-formulations of their drugs with COBI in it. These include Prezista from Janssen Therapeutics and Reyataz from Bristol-Myers Squibb (BMS). While the agreement with BMS is for a boosted Reyataz pill, the agreement with Janssen is for a boosted Prezista pill, as well as a complete HIV regimen in one tablet that includes Prezista (darunavir), cobicistat, emtricitabine, and Gilead's GS-7340, an investigational pro-drug (inactive substance that metabolizes into active form in the body) of its popular Viread (tenofovir). Reyataz boosted by COBI has been studied compared to Norvir-boosted Reyataz. Gilead will submit the results from its 114 study (atazanavir/emtricitabine/tenofovir/cobicistat vs. atazanavir/emtricitabine/tenofovir/ritonavir) at a scientific conference this year. The 48-week data from this study showed that 85% of patients taking the cobicistat formulation achieved undetectable viral load of less than 50 copies/mL, compared to 87% of patients taking the Norvir one. At 48 weeks, there was similar efficacy, safety, and tolerability. See package insert when available for more complete information on potential side effects and interactions.
Cobicistat is expected to be the first approved non-Norvir boosting agent, to be combined with PIs and elvitegravir. Its main advantage over Norvir is likely to be co-formulation: while Norvir is currently co-formulated only with lopinavir in the form of Kaletra, cobicistat may eventually be co-formulated with elvitegravir (including a single-tablet "Quad" regimen that will also contain tenofovir and emtricitabine), atazanavir, and darunavir. A second "quad" tablet containing darunavir, cobicistat, emtricitabine, and an investigational tenofovir pro-drug is also being developed, which, if successful, will be the first single-tablet PI-based regimen.
-- Joel Gallant, M.D., M.P.H.
Talk about hopes and expectations being too high! Many of us were hoping this would rid us of the typical boosters that cause diarrhea -- the worst side effect there is, especially if you're out and about and an accident happens! Unfortunately, this new booster has many of the same side effects as the existing Norvir booster. One glimmer of hope (or a silver lining if you will) will be in co-formulations. Having everything in one pill helps reduce pill burden, and reduce co-pays and deductibles for those having to pay. At least we're getting more options out there, and that is always better.
-- Joey Wynn