– DISCOVER Trial Meets Primary and Secondary Endpoints and Will Support Supplemental Regulatory Filing for Descovy for Pre-Exposure Prophylaxis (PrEP) –
FOSTER CITY, CA, USA I March 06, 2019 I Gilead Sciences, Inc. (NASDAQ: GILD) today announced results from the DISCOVER trial, a two-year Phase 3 randomized, controlled, double-blind study evaluating the safety and efficacy of the investigational use of once-daily Descovy® (emtricitabine 200 mg and tenofovir alafenamide 25mg) for HIV pre-exposure prophylaxis (PrEP), compared with Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg), in men who have sex with men and transgender women at risk for sexually acquired HIV infection.
In a late-breaker oral abstract presented today at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, 5,387 study participants were randomized in a 1:1 ratio and received either Descovy or Truvada. Among the 2,694 participants (4,370 patient-years) who were at risk of HIV-1 infection and received once-daily Descovy, seven HIV infections (HIV incidence 0.16/100 person-years (PY)) were reported. Among the 2,693 participants (4,386 patient-years) who were at risk of HIV-1 infection and received Truvada, 15 HIV infections (0.34/100 PY) were reported. Descovy met the pre-established criteria for non-inferiority to Truvada using a stringent rate ratio statistical comparison, as demonstrated by the upper bound of the 95 percent confidence interval for HIV-1 infection rate ratio being less than the predefined non-inferiority margin of 1.62/100 PY. Additionally, statistically significant advantages with respect to bone and renal laboratory parameters were observed for participants receiving Descovy as compared with those receiving Truvada, which were pre-specified secondary endpoints.
“As the largest HIV prevention trial conducted to date, the DISCOVER trial results clearly demonstrate Descovy for PrEP™ achieved a clinical profile similar to the high efficacy of Truvada and a more favorable bone and renal safety profile,” said John McHutchison, AO, MD, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. “We look forward to filing regulatory applications for Descovy for the PrEP indication as a potential important new option to prevent individuals from becoming infected and contribute to the achievement of national and global HIV prevention goals.”
In the U.S., Descovy is approved in combination with other antiretroviral agents for the treatment of HIV infection in patients weighing ≥ 35 kg and is not indicated for PrEP. Truvada is indicated in combination with safer sex practices for HIV PrEP to reduce the risk of sexually acquired HIV in at-risk adults and adolescents weighing ≥ 35 kg. Descovy and Truvada each have a Boxed Warning in their respective product labels regarding the risk of post-treatment acute exacerbation of hepatitis B; the Truvada label also carries a Boxed Warning for the risk of drug resistance with PrEP in undiagnosed early HIV infection. See below for Important Safety Information and complete Indications.
“The DISCOVER trial enrolled more than 5,000 men who have sex with men and transgender women who were at risk of acquiring HIV in order to gain insights about the efficacy and safety of Descovy and Truvada for PrEP in populations with some of the highest rates of HIV infection,” said Brad Hare, MD, Chief of Infectious Diseases at Kaiser-Permanente, San Francisco. “The very low incidence of HIV in both treatment arms, combined with Descovy’s improved renal and bone safety as compared with Truvada, demonstrate that Descovy for PrEP may help build on the progress made by Truvada, a proven public health tool in the fight against HIV.”
All DISCOVER study participants were adult cis-men who have sex with men or transgender women who had risk of HIV infection through documented high-risk sexual behavior at study entry. Sexually transmitted infection (STI) screening results also demonstrated that participants maintained their sexual risk behavior during the study. Per study protocol, all participants were tested for STIs every three months at three anatomic sites (oropharynx, urethra, rectum), and all received medical treatment and contact tracing as appropriate. Overall, during the study, 57 percent were diagnosed with gonorrhea or chlamydia (from any anatomic site), 42 percent were diagnosed with rectal gonorrhea or rectal chlamydia, and 10 percent were diagnosed with syphilis.
Among the 22 HIV infections reported in the DISCOVER study, five were likely acquired before study entry, 15 occurred in the setting of low or undetectable intracellular drug levels, and two occurred with intermediate or expected intracellular drug levels detected.
Descovy and Truvada were well tolerated and had low discontinuation rates due to adverse events of 1.3 percent and 1.8 percent, respectively. The most common (>15 percent in either group) adverse events were similar in each group and included anal chlamydia, oropharyngeal gonorrhea and rectal gonorrhea.
Study participants randomized to receive Descovy had improved bone and renal safety outcomes relative to those who received Truvada. Bone mineral density (BMD) was tested in a subset of 383 participants. The percent change in spine BMD was reduced by 1.1 percent for those on Truvada while it increased by 0.5 percent in those on Descovy (p<0.001) at Week 48. The percent change in hip BMD was reduced by 1.0 percent in those on Truvada while it was increased by 0.2 percent for those on Descovy (p<0.001) at Week 48.
All DISCOVER study participants had renal laboratory testing at every visit. The creatinine clearance (estimated glomerular filtration rate) increased by 1.8 mL/min for those randomized to Descovy while it was reduced by 2.3 mL/min in those who received Truvada (p<0.001) at Week 48. There were no cases of Fanconi Syndrome in the Descovy arm while one case was reported in the Truvada arm, which led to premature discontinuation of study drug.
The use of Descovy for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally.
INDICATION
Descovy is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in patients weighing at least 35 kg.
Descovy is also indicated, in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.
Limitations of Use:
Descovy is not indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV-1 infection.
INDICATION
Truvada for PrEP (pre-exposure prophylaxis) is indicated to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) who are at risk for HIV, when used in combination with safer sex practices. HIV-negative status must be confirmed immediately prior to initiation
- If clinical symptoms of acute HIV-1 infection are present and recent exposures (<1 month) are suspected, delay initiation for at least 1 month until HIV-negative status is reconfirmed. Alternatively, confirm HIV-negative status with a test cleared by FDA to aid in the diagnosis of acute HIV-1 infection
Individuals at risk for sexually acquired HIV-1 may include those:
- With HIV-1 infected partner(s), or
- Who engage in sexual activity in a high prevalence area or social network and have additional risk factors, such as: inconsistent or no condom use, diagnosis of sexually transmitted infections (STIs), exchange of sex for commodities, use of illicit drugs or alcohol dependence, incarceration, or sexual partners of unknown HIV status with any of these risk factors
About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.
For nearly 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, testing and linkage to care, and cure research. Today, it’s estimated that more than 11.5 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com.
SOURCE: Gilead Sciences
Post Views: 54
– DISCOVER Trial Meets Primary and Secondary Endpoints and Will Support Supplemental Regulatory Filing for Descovy for Pre-Exposure Prophylaxis (PrEP) –
FOSTER CITY, CA, USA I March 06, 2019 I Gilead Sciences, Inc. (NASDAQ: GILD) today announced results from the DISCOVER trial, a two-year Phase 3 randomized, controlled, double-blind study evaluating the safety and efficacy of the investigational use of once-daily Descovy® (emtricitabine 200 mg and tenofovir alafenamide 25mg) for HIV pre-exposure prophylaxis (PrEP), compared with Truvada® (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg), in men who have sex with men and transgender women at risk for sexually acquired HIV infection.
In a late-breaker oral abstract presented today at the Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, 5,387 study participants were randomized in a 1:1 ratio and received either Descovy or Truvada. Among the 2,694 participants (4,370 patient-years) who were at risk of HIV-1 infection and received once-daily Descovy, seven HIV infections (HIV incidence 0.16/100 person-years (PY)) were reported. Among the 2,693 participants (4,386 patient-years) who were at risk of HIV-1 infection and received Truvada, 15 HIV infections (0.34/100 PY) were reported. Descovy met the pre-established criteria for non-inferiority to Truvada using a stringent rate ratio statistical comparison, as demonstrated by the upper bound of the 95 percent confidence interval for HIV-1 infection rate ratio being less than the predefined non-inferiority margin of 1.62/100 PY. Additionally, statistically significant advantages with respect to bone and renal laboratory parameters were observed for participants receiving Descovy as compared with those receiving Truvada, which were pre-specified secondary endpoints.
“As the largest HIV prevention trial conducted to date, the DISCOVER trial results clearly demonstrate Descovy for PrEP™ achieved a clinical profile similar to the high efficacy of Truvada and a more favorable bone and renal safety profile,” said John McHutchison, AO, MD, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. “We look forward to filing regulatory applications for Descovy for the PrEP indication as a potential important new option to prevent individuals from becoming infected and contribute to the achievement of national and global HIV prevention goals.”
In the U.S., Descovy is approved in combination with other antiretroviral agents for the treatment of HIV infection in patients weighing ≥ 35 kg and is not indicated for PrEP. Truvada is indicated in combination with safer sex practices for HIV PrEP to reduce the risk of sexually acquired HIV in at-risk adults and adolescents weighing ≥ 35 kg. Descovy and Truvada each have a Boxed Warning in their respective product labels regarding the risk of post-treatment acute exacerbation of hepatitis B; the Truvada label also carries a Boxed Warning for the risk of drug resistance with PrEP in undiagnosed early HIV infection. See below for Important Safety Information and complete Indications.
“The DISCOVER trial enrolled more than 5,000 men who have sex with men and transgender women who were at risk of acquiring HIV in order to gain insights about the efficacy and safety of Descovy and Truvada for PrEP in populations with some of the highest rates of HIV infection,” said Brad Hare, MD, Chief of Infectious Diseases at Kaiser-Permanente, San Francisco. “The very low incidence of HIV in both treatment arms, combined with Descovy’s improved renal and bone safety as compared with Truvada, demonstrate that Descovy for PrEP may help build on the progress made by Truvada, a proven public health tool in the fight against HIV.”
All DISCOVER study participants were adult cis-men who have sex with men or transgender women who had risk of HIV infection through documented high-risk sexual behavior at study entry. Sexually transmitted infection (STI) screening results also demonstrated that participants maintained their sexual risk behavior during the study. Per study protocol, all participants were tested for STIs every three months at three anatomic sites (oropharynx, urethra, rectum), and all received medical treatment and contact tracing as appropriate. Overall, during the study, 57 percent were diagnosed with gonorrhea or chlamydia (from any anatomic site), 42 percent were diagnosed with rectal gonorrhea or rectal chlamydia, and 10 percent were diagnosed with syphilis.
Among the 22 HIV infections reported in the DISCOVER study, five were likely acquired before study entry, 15 occurred in the setting of low or undetectable intracellular drug levels, and two occurred with intermediate or expected intracellular drug levels detected.
Descovy and Truvada were well tolerated and had low discontinuation rates due to adverse events of 1.3 percent and 1.8 percent, respectively. The most common (>15 percent in either group) adverse events were similar in each group and included anal chlamydia, oropharyngeal gonorrhea and rectal gonorrhea.
Study participants randomized to receive Descovy had improved bone and renal safety outcomes relative to those who received Truvada. Bone mineral density (BMD) was tested in a subset of 383 participants. The percent change in spine BMD was reduced by 1.1 percent for those on Truvada while it increased by 0.5 percent in those on Descovy (p<0.001) at Week 48. The percent change in hip BMD was reduced by 1.0 percent in those on Truvada while it was increased by 0.2 percent for those on Descovy (p<0.001) at Week 48.
All DISCOVER study participants had renal laboratory testing at every visit. The creatinine clearance (estimated glomerular filtration rate) increased by 1.8 mL/min for those randomized to Descovy while it was reduced by 2.3 mL/min in those who received Truvada (p<0.001) at Week 48. There were no cases of Fanconi Syndrome in the Descovy arm while one case was reported in the Truvada arm, which led to premature discontinuation of study drug.
The use of Descovy for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally.
INDICATION
Descovy is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in patients weighing at least 35 kg.
Descovy is also indicated, in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.
Limitations of Use:
Descovy is not indicated for use as pre-exposure prophylaxis (PrEP) to reduce the risk of acquiring HIV-1 infection.
INDICATION
Truvada for PrEP (pre-exposure prophylaxis) is indicated to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) who are at risk for HIV, when used in combination with safer sex practices. HIV-negative status must be confirmed immediately prior to initiation
- If clinical symptoms of acute HIV-1 infection are present and recent exposures (<1 month) are suspected, delay initiation for at least 1 month until HIV-negative status is reconfirmed. Alternatively, confirm HIV-negative status with a test cleared by FDA to aid in the diagnosis of acute HIV-1 infection
Individuals at risk for sexually acquired HIV-1 may include those:
- With HIV-1 infected partner(s), or
- Who engage in sexual activity in a high prevalence area or social network and have additional risk factors, such as: inconsistent or no condom use, diagnosis of sexually transmitted infections (STIs), exchange of sex for commodities, use of illicit drugs or alcohol dependence, incarceration, or sexual partners of unknown HIV status with any of these risk factors
About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.
For nearly 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, testing and linkage to care, and cure research. Today, it’s estimated that more than 11.5 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com.
SOURCE: Gilead Sciences
Post Views: 54
