Gilead Sciences, Inc. (Nasdaq: GILD) today presented longer-term
results from the DISCOVER trial of Descovy (emtricitabine 200 mg
and tenofovir alafenamide 25 mg tablets, F/TAF) for pre-exposure
prophylaxis (PrEP), demonstrating continued non-inferior efficacy
and continued favorable changes in key markers of renal and bone
safety at Week 96 compared with Truvada® (emtricitabine 200 mg and
tenofovir disoproxil fumarate 300 mg, F/TDF) for PrEP. These
results were achieved in the overall study population of men and
transgender women at risk for HIV infection, as well as in study
sub-populations of participants age 50 and older, those younger
than 25 years, and those with moderate renal impairment. A separate
analysis of the DISCOVER trial demonstrated that Descovy and
Truvada were effective and well-tolerated in Black and
Hispanic/Latinx participants. These data were presented at the 2020
Conference on Retroviruses and Opportunistic Infections (CROI) in
Boston.
“At Gilead, we believe continued scientific innovation is
essential to altering the future of the HIV epidemic,” said Diana
Brainard, MD, Senior Vice President, HIV and Emerging Viral
Infections, Gilead Sciences. “The longer-term efficacy and safety
outcomes from the DISCOVER trial continue to demonstrate that
Descovy is effective for HIV prevention with non-inferior efficacy
to Truvada, and that Descovy has an improved bone and renal safety
profile compared with Truvada.”
In addition to new data from the DISCOVER trial, the company
also presented the results of a preclinical study with an
investigational combination of bictegravir, emtricitabine and
tenofovir alafenamide (BIC+F/TAF; 100+200/25 mg) for event-driven
post-exposure prophylaxis (PEP).
In the United States, Descovy for PrEP® is indicated to reduce
the risk of sexually acquired HIV-1 infection in at-risk adults and
adolescents weighing at least 35 kg, excluding individuals at risk
of HIV-1 from receptive vaginal sex because effectiveness in this
population has not been evaluated.
Descovy has a Boxed Warning in its U.S. product label regarding
the risk of drug resistance when used for PrEP in undiagnosed early
HIV infection, and the risk of post-treatment acute exacerbation of
hepatitis B. See below for Indication and Important Safety
Information.
96-Week Safety Data from the DISCOVER Trial
This 96-week analysis of the DISCOVER trial (Oral 2940)
demonstrated significant differences in key markers of bone and
renal safety in study participants across different age groups.
These differences were also observed in the overall population, in
addition to differences in lipid parameters and change in baseline
weight. The long-term clinical significance of these differences in
renal, bone and lipid parameters are not known; however, these
measures are important to consider as people at risk increasingly
use PrEP for longer periods of time.
At Week 96, statistically significant differences in
measurements of renal safety favoring Descovy were observed in the
overall trial population, as well as in older participants and in
those with moderate renal impairment (baseline eGFR=60-≤90 mL/min).
In participants older than 50 years of age, those receiving Descovy
showed a smaller decrease in median estimated glomerular filtration
rate (eGFR) compared with those receiving Truvada (-1 mL/min vs. -6
mL/min) at Week 96. Key differences favoring Descovy were also
observed in markers of proximal tubular function
(β2-microglobulin:creatinine ratio and retinol binding
protein:creatinine ratio). Among participants with moderate renal
impairment, those randomized to Descovy also had smaller changes in
eGFR and markers of proximal tubular function. In this sub-group,
eGFR increased by 3 mL/min among those taking Descovy and decreased
by 1 mL/min in those taking Truvada.
The analysis also found changes in bone mineral density (BMD)
favoring Descovy in the overall trial population and among
participants younger than 25 years of age. At Week 96 in
participants younger than 25 years, spine BMD increased by 1.39
percent in the Descovy group and decreased by 1.2 percent in the
Truvada group. Hip BMD increased 1.21 percent from baseline in the
Descovy group and decreased by 1.7 percent in the Truvada
group.
Study participants receiving Descovy had stable lipid levels
through 96 weeks, whereas those receiving Truvada had decreases in
lipid levels after 48 and 96 weeks. Fasting glucose levels were
similar between the 2 groups. Participants in the Truvada group
showed smaller mean weight increases than those in the Descovy
group (+0.5 kg vs. +1.7 kg at Week 96). These findings are
consistent with the lower lipid levels and decreased weight
previously observed with TDF.
“These data continue to support the role of Descovy for PrEP as
an option for a range of appropriate individuals at risk for HIV
infection,” said Onyema Ogbuagu, MD, FACP, Director of HIV Clinical
Trials program at Yale School of Medicine. “We are especially
pleased to see that Descovy, unlike Truvada, did not result in a
decrease in bone mineral density among younger participants and
that more favorable measures of renal function were observed among
study participants including older individuals and those with
moderate renal impairment.”
Additional Data and Results from the DISCOVER Trial
On Monday, March 9, data were presented from 96-week follow-up
of Black (n=474; 9%) and Hispanic/Latinx (n=1,318; 24%)
participants in the DISCOVER trial (Poster 4033), which showed that
both Descovy and Truvada were effective and well-tolerated in Black
and Hispanic/Latinx participants.
Additional results presented from the DISCOVER trial included an
analysis of transgender female trial participants who were taking
high-dose gender-affirming hormone therapy (n=27) during the study
(Poster 4018). This analysis of concomitant hormone therapy on the
pharmacokinetics, efficacy and safety profile of Descovy or Truvada
builds on the data from the dedicated Phase 1 studies that
demonstrated lack of an effect of oral contraceptive hormones on
the plasma exposure of TAF, TFV and FTC, and the lack of effect of
plasma TAF, TFV, and FTC on ethinyl estradiol exposures, FSH, LH,
or progesterone levels.
An analysis of drug levels and adherence in the DISCOVER trial
(Poster 3815) will be presented tomorrow, March 11.
Descovy, Truvada, and BIC/FTC/TAF do not prevent other sexually
transmitted infections or cure HIV or AIDS.
About the DISCOVER Trial
The DISCOVER trial is a multi-year global Phase 3 registrational
clinical trial evaluating the safety and efficacy of once-daily
Descovy for PrEP compared with Truvada for PrEP® in men and
transgender women who have sex with men and are at risk for
sexually acquired HIV infection. The primary analysis of the study
was at Week 48; the Week 96 analysis was a prespecified secondary
analysis. At both Weeks 48 and 96, Descovy for PrEP demonstrated
non-inferior efficacy to Truvada for PrEP.
Important U.S. Safety Information and
Indication for Descovy for PrEP
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY
FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT
ACUTE EXACERBATION OF HEPATITIS B
- DESCOVY FOR PrEP must be prescribed only to patients
confirmed to be HIV negative immediately prior to initiation and at
least every 3 months during use. Drug-resistant HIV-1 variants have
been identified with use of emtricitabine/tenofovir disoproxil
fumarate (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1
infection. Do not initiate if signs or symptoms of acute HIV-1
infection are present unless HIV-negative status is
confirmed
- Severe acute exacerbations of hepatitis B have been reported
in patients infected with hepatitis B virus (HBV) who discontinued
products containing FTC and/or TDF and may occur with
discontinuation of DESCOVY. Closely monitor hepatic function with
both clinical and laboratory follow-up for at least several months
in patients with HBV who discontinue DESCOVY. If appropriate,
anti-hepatitis B therapy may be warranted
Contraindication
- DESCOVY FOR PrEP is contraindicated in patients with unknown or
positive HIV status
Warnings and precautions
- Comprehensive management to reduce risks:
- Use DESCOVY FOR PrEP to reduce the risk of HIV-1 infection as
part of a comprehensive strategy that includes adherence to daily
dosing and safer sex practices, including condoms, to reduce the
risk of sexually transmitted infections (STIs)
- HIV-1 risk factors: Behavioral, biological, or
epidemiologic HIV-1 risk factors may include, but are not limited
to: condomless sex, past or current STIs, self-identified HIV risk,
having sexual partners of unknown HIV-1 viremic status, or sexual
activity in a high-prevalence area or network
- Reduce STI risk: Counsel on the use of STI prevention
measures (e.g., consistent and correct condom use, knowledge of
partner’s HIV-1 viremic status, regular testing for STIs)
- Reduce potential for drug resistance: Only prescribe
DESCOVY FOR PrEP to patients confirmed to be HIV negative
immediately prior to initiation, at least every 3 months while
taking DESCOVY, and upon an STI diagnosis. HIV-1 resistance
substitutions may emerge in patients with undetected HIV-1
infection who are taking only DESCOVY because DESCOVY alone is not
a complete regimen for treating HIV-1
- Some HIV tests may not detect acute HIV infection. Prior to
initiating DESCOVY FOR PrEP, ask patients about potential recent
exposure events. If recent (<1 month) exposures are reported or
suspected, or symptoms of acute HIV infection (e.g., fever,
fatigue, myalgia, skin rash) are present, confirm HIV-negative
status with a test approved by the FDA for use in the diagnosis of
acute HIV infection
- If HIV-1 infection is suspected or if symptoms of acute
infection are present while taking DESCOVY FOR PrEP, convert the
DESCOVY FOR PrEP regimen to a complete HIV treatment regimen until
HIV-negative status is confirmed by a test approved by the FDA for
use in the diagnosis of acute HIV infection
- Counsel on adherence: Counsel patients to strictly
adhere to daily dosing, as efficacy is strongly correlated with
adherence. Some patients, such as adolescents, may benefit from
more frequent visits and counseling
- New onset or worsening renal impairment: Cases of acute
renal failure and Fanconi syndrome have been reported with the use
of tenofovir prodrugs. Do not initiate DESCOVY in patients with
estimated creatinine clearance (CrCl) <30 mL/min. Patients with
impaired renal function and/or taking nephrotoxic agents (including
NSAIDs) are at increased risk of renal-related adverse reactions.
Discontinue DESCOVY in patients who develop clinically significant
decreases in renal function or evidence of Fanconi syndrome.
Monitor renal function in all patients (see Dosage and
Administration section)
- Lactic acidosis and severe hepatomegaly with steatosis:
Fatal cases have been reported with the use of nucleoside analogs,
including FTC and TDF. Discontinue use if clinical or laboratory
findings suggestive of lactic acidosis or pronounced hepatotoxicity
develop, including hepatomegaly and steatosis in the absence of
marked transaminase elevations
Adverse reactions
- Most common adverse reactions (≥2%) in the DESCOVY FOR
PrEP clinical trial were diarrhea, nausea, headache, fatigue, and
abdominal pain
Drug interactions
- Prescribing information: Consult the full Prescribing
Information for DESCOVY for more information, warnings, and
potentially significant drug interactions, including clinical
comments
- Metabolism: Drugs that inhibit P-gp can increase the
concentrations of tenofovir alafenamide (TAF), a component of
DESCOVY. Drugs that induce P-gp can decrease the concentrations of
TAF, which may lead to loss of efficacy
- Drugs affecting renal function: Coadministration of
DESCOVY with drugs that reduce renal function or compete for active
tubular secretion may increase concentrations of FTC and tenofovir
and the risk of adverse reactions
Dosage and administration
- Dosage: One tablet taken once daily with or without
food
- HIV screening: Test for HIV-1 infection immediately
prior to initiating, at least every 3 months during use, and upon
diagnosis of an STI (see Warnings and Precautions section)
- HBV screening: Test for HBV infection prior to or when
initiating DESCOVY
- Renal impairment and monitoring: Not recommended in
patients with creatinine clearance (CrCl) <30 mL/min. Prior to
or when initiating DESCOVY, and during use on a clinically
appropriate schedule, assess serum creatinine, CrCl, urine glucose,
and urine protein in all patients. In patients with chronic kidney
disease, assess serum phosphorus
INDICATION
DESCOVY for PrEP is indicated in at-risk adults and adolescents
(≥35 kg) to reduce the risk of sexually acquired HIV-1 infection,
excluding individuals at risk from receptive vaginal sex.
HIV-1–negative status must be confirmed immediately prior to
initiation.
- Limitation of Use: DESCOVY FOR PrEP is not indicated in
individuals at risk of HIV-1 from receptive vaginal sex because
effectiveness in this population has not been evaluated.
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 more than 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 12 million people living with HIV globally
receive antiretroviral therapy provided by Gilead or one of the
company’s manufacturing partners.
Forward-Looking Statement
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 possibility of unfavorable results from ongoing and
additional clinical trials involving Descovy for PrEP, Truvada for
PrEP and the combination of BIC/FTC/TAF for post-exposure
prophylaxis, and the possibility that we are unable to complete one
or more of such trials on the currently anticipated timelines or at
all. In addition, it is possible that Gilead may make a strategic
decision to discontinue development of BIC/FTC/TAF for
post-exposure prophylaxis, and as a result, it may never be
successfully commercialized. All statements other than statements
of historical fact are statements that could be deemed
forward-looking statements. 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 Annual Report
on Form 10-K for the year ended December 31, 2019, as filed with
the U.S. Securities and Exchange Commission. All forward-looking
statements are based on information currently available to Gilead,
and Gilead assumes no obligation to update any such forward-looking
statements.
U.S. full Prescribing Information for Descovy
and Truvada, including BOXED WARNINGS, is available at
www.gilead.com
Descovy, Descovy for PrEP, Truvada, Truvada for
PrEP and Gilead are trademarks of Gilead Sciences, Inc. or its
related companies.
For more information on Gilead Sciences, please
visit the company’s website at www.gilead.com, follow Gilead on
Twitter (@GileadSciences) or call Gilead Public Affairs at
1-800-GILEAD-5 or 1-650-574-3000.
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version on businesswire.com: https://www.businesswire.com/news/home/20200310005729/en/
Douglas Maffei, PhD, Investors (650) 522-2739
Brian Plummer, Media (650) 524-7708
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