July 24, 2012
Gilead’s Boosting Agent Cobicistat for HIV Therapy as Effective as Ritonavir in Pivotal Phase 3 Study
“These data demonstrate that cobicistat may be an effective option for
boosting the potency of HIV regimens that are based on protease
In the trial (Study 114), treatment-naïve adult patients received either
cobicistat or ritonavir for 48 weeks. All patients also received
atazanavir (a protease inhibitor) plus Truvada®
(emtricitabine and tenofovir disoproxil fumarate). At 48 weeks, the
study found that 85 percent of patients on the cobicistat-containing
regimen compared to 87 percent of patients on the ritonavir-containing
regimen achieved HIV RNA (viral load) levels less than 50 copies/mL,
based on the
“We believe that cobicistat has a central role to play in boosting
protease-based HIV therapies,” said
Gilead submitted a New Drug Application to
Gilead announced topline results for Study 114 on
About Study 114
Study 114 is a randomized, double-blind Phase 3 clinical trial comparing
the efficacy and safety of cobicistat-boosted atazanavir versus
ritonavir-boosted atazanavir, each administered with Truvada, over a
192-week period at more than 200 study sites in
The primary endpoint of the study is the proportion of patients
achieving HIV RNA levels of less than 50 copies/mL at 48 weeks of
treatment, as determined by the
At baseline, patients in the cobicistat and ritonavir arms had a median HIV RNA of 4.78 log10 copies/mL and 4.84 log10 copies/mL and mean CD4 cell count of 353 cells/mm3 and 351 cells/mm3, respectively.
Mean increases in CD4 cell counts were 213 cells/mm3 for cobicistat patients and 219 cells/mm3 for ritonavir patients at 48 weeks (p=0.67). Virologic failure rates were low in both arms – 6 percent for patients receiving cobicistat and 4 percent for those receiving ritonavir. Drug resistance was also low – two patients developed an NRTI resistance mutation in the cobicistat arm, and none in the ritonavir arm.
Incidence of laboratory abnormalities (Grade 3-4) was similar in both arms of the study. Laboratory abnormalities (Grade 3-4) occurring in at least one percent of patients in either treatment arm included hyperbilirubinemia, creatine kinase, hematuria, ALT, AST, amylase, glycosuria, hyperglycemia, GGT and neutropenia. Only hyperbilirubinemia (65 percent in the cobicistat arm vs. 57 percent in the ritonavir arm, p=0.023) and creatine kinase (6 percent in both arms) occurred in more than 5 percent of patients in either arm.
The most common adverse events occurring in greater than or equal to 10 percent of patients in either treatment arm included jaundice (21 percent in the cobicistat arm vs. 16 percent in the ritonavir arm), ocular icterus (18 percent in both arms), nausea (18 percent vs. 16 percent), diarrhea (15 percent vs. 20 percent), headache (11 percent vs. 16 percent), nasopharyngitis (11 percent vs. 15 percent), hyperbilirubinemia (11 percent vs. 10 percent) and upper respiratory infection (10 percent vs. 8 percent).
The median increases in serum creatinine were 0.13 mg/dL for the cobicistat arm and 0.09 mg/dL for the ritonavir arm at 48 weeks (p<0.001). Discontinuation rates due to renal adverse events were low and comparable in both arms (1.7 percent in the cobicistat arm vs. 1.4 percent in the ritonavir arm).
Median changes from baseline to Week 48 in total cholesterol were +4 mg/dL and +10 mg/dL (p=0.081); median changes in low-density lipoprotein (LDL or “bad” cholesterol) were +5 mg/dL and +8 mg/dL (p=0.32); and median changes in triglycerides were +16 mg/dL and +24 mg/dL (p=0.63) for patients in the cobicistat and ritonavir arms, respectively. Median increases in high-density lipoprotein (HDL or “good” cholesterol) were similar in the cobicistat and ritonavir arms (+4 mg/dL vs. +3 mg/dL, p=0.69).
Study 114 is ongoing in a blinded fashion. Additional information about the study can be found at www.clinicaltrials.gov.
Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. Unlike ritonavir, cobicistat acts only as a pharmacoenhancer and has no antiviral activity. Pharmacokinetic studies have demonstrated that cobicistat boosts the widely prescribed protease inhibitors atazanavir and darunavir.
The Quad contains elvitegravir, cobicistat (a pharmacoenhancing or
“boosting” agent that enables once-daily dosing of elvitegravir), and
Truvada (emtricitabine and tenofovir disoproxil fumarate). In
Cobicistat, elvitegravir and the Quad are investigational products and their safety and efficacy have not yet been established.
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that Gilead may fail to obtain approvals for cobicistat and Quad
from regulatory authorities and any marketing approval, if granted, may
have significant limitations on their use. As a result, cobicistat and
Quad may never be successfully commercialized. In addition, Gilead may
make a strategic decision to discontinue development of cobicistat or
Quad if, for example, it believes commercialization will be difficult
relative to other opportunities in its pipeline. Further, Gilead may be
unsuccessful in developing and commercializing fixed-dose combinations
that combine cobicistat with other protease inhibitors, including
darunavir and atazanavir. These risks, uncertainties and other factors
could cause actual results to differ materially from those referred to
in the forward-looking statements. The reader is cautioned not to rely
on these forward-looking statements. These and other risks are described
in detail in Gilead's Quarterly Report on Form 10-Q for the quarter
U.S. full prescribing information for Truvada is available at www.Truvada.com.
Truvada is a registered trademark of
For more information on
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Erin Rau, 650-522-5635 (Media)