– Efficacy and Safety Profile of Once-Daily
Vemlidy Demonstrated in Children Six Years of Age (Weighing at
Least 25kg) and Older –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
U.S. Food and Drug Administration (FDA) has approved the
supplemental new drug application (sNDA) for Vemlidy® (tenofovir
alafenamide) 25 mg tablets as a once-daily treatment for chronic
hepatitis B virus (HBV) infection in pediatric patients six years
of age and older and weighing at least 25 kg with compensated liver
disease.
Vemlidy is a targeted prodrug of tenofovir that was approved by
the FDA in 2016 as a once-daily treatment for adults with chronic
HBV infection with compensated liver disease. In 2022, the FDA
approved Vemlidy for the treatment of chronic HBV infection in
pediatric patients 12 years of age and older with compensated liver
disease. Vemlidy is recommended as a preferred or first-line
treatment for adults with chronic HBV with compensated liver
disease by the American Association for the Study of Liver Diseases
(AASLD) and European Association for the Study of the Liver (EASL)
guidelines.
“Chronic hepatitis B can have a significant and lasting impact
on the health of children. If left untreated, hepatitis B can lead
to liver cirrhosis and liver cancer,” said Chaun-Hao Lin, MD,
Associate Professor of Clinical Pediatrics Krek School of Medicine
of USC. “As a clinician, I am well aware of the critical importance
of promptly treating this disease to avoid possible complications
and liver damage. The clinical trial demonstrated that tenofovir
alafenamide may represent an effective treatment option for
children as young as six years old affected by this chronic
disease.”
Vemlidy’s approval in this pediatric patient population is
supported by Week 96 data from a Phase 2 clinical trial (Trial
1092) comparing treatment with Vemlidy 25 mg to placebo among 18
treatment-naïve and treatment-experienced patients aged 6 to less
than 12 years weighing at least 25 kg (Cohort 2, Group 1).
Participants in the Vemlidy group and in the placebo group who
switched to open-label Vemlidy after Week 24 demonstrated
progressive increases in the rates of virological suppression
through Week 96 overall and within both study cohorts (children and
adolescents).
“The expanded indication for Vemlidy for the treatment of
children as young as six years old is a testament to the safety,
tolerability and efficacy profile of this therapy,” said Frank
Duff, MD, Senior Vice President, Virology Therapeutic Area Head,
Gilead Sciences. “Effective and tolerable options for children
require our best science and a dedicated focus. The work of our
Gilead Pediatric Center of Excellence is responsible for
coordinating pediatric clinical trials for treatments for cancer,
HIV, hepatitis B, and COVID-19 and we will continue our research to
help address unmet treatment needs for children.”
Vemlidy has a boxed warning in its product label regarding
post-treatment severe acute exacerbation of hepatitis B. See below
for important safety information.
U.S. IMPORTANT SAFETY INFORMATION AND INDICATION FOR THE USE
OF VEMLIDY
BOXED WARNING: POSTTREATMENT SEVERE ACUTE EXACERBATION OF
HEPATITIS B
Discontinuation of anti-hepatitis B therapy, including
VEMLIDY, may result in severe acute exacerbations of hepatitis B.
Hepatic function should be monitored closely with both clinical and
laboratory follow-up for at least several months in patients who
discontinue anti-hepatitis B therapy, including VEMLIDY. If
appropriate, resumption of anti-hepatitis B therapy may be
warranted.
Warnings and Precautions
- Risk of Development of HIV-1 Resistance in HBV/HIV-1
Coinfected Patients: Due to this risk, VEMLIDY alone should not
be used for the treatment of HIV-1 infection. Safety and efficacy
of VEMLIDY have not been established in HBV/HIV-1 coinfected
patients. HIV antibody testing should be offered to all
HBV-infected patients before initiating therapy with VEMLIDY, and
if positive, an appropriate antiretroviral combination regimen that
is recommended for HBV/HIV-1 coinfected patients should be
used.
- New Onset or Worsening Renal Impairment: Postmarketing
cases of renal impairment, including acute renal failure, proximal
renal tubulopathy (PRT), and Fanconi syndrome, have been reported
with TAF-containing products. Patients with impaired renal function
and/or taking nephrotoxic agents (including NSAIDs) are at
increased risk of renal-related adverse reactions. Discontinue
VEMLIDY 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.
- Lactic Acidosis and Severe Hepatomegaly with Steatosis:
Fatal cases have been reported with the use of nucleoside analogs,
including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY
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 events in the week 96 pediatric population
reported in ≥5% were: nasopharyngitis, headache, COVID-19, pyrexia,
diarrhea, upper respiratory tract infection, cough, respiratory
tract infection viral, abdominal pain upper. Overall, abdominal
pain upper and metabolic nephropathy were the only study
drug–related adverse events, which occurred in > 1 participant,
reported in 2.3% (2/88 participants) each.
Drug Interactions
- Coadministration of VEMLIDY with drugs that reduce renal
function or compete for active tubular secretion may increase
concentrations of tenofovir and the risk of adverse reactions.
- Coadministration of VEMLIDY is not recommended with the
following: oxcarbazepine, phenobarbital, phenytoin, rifabutin,
rifampin, rifapentine, or St. John’s wort. Such coadministration is
expected to decrease the concentration of tenofovir alafenamide,
reducing the therapeutic effect of VEMLIDY. Drugs that strongly
affect P-glycoprotein (P-gp) and breast cancer resistance protein
(BCRP) activity may lead to changes in VEMLIDY absorption.
- Coadministration of VEMLIDY with carbamazepine, the tenofovir
alafenamide dose should be increased to two tablets once
daily.
Consult the full prescribing information for VEMLIDY for more
information on potentially significant drug interactions, including
clinical comments.
Dosage and Administration
- Testing Prior to Initiation: HIV infection.
- Prior to or When Initiating, and During Treatment: On a
clinically appropriate schedule, assess serum creatinine, estimated
creatinine clearance, urine glucose, and urine protein in all
patients. In patients with chronic kidney disease, also assess
serum phosphorus.
- Dosage: 1 tablet taken once daily with food.
- Renal Impairment: Not recommended in patients with
end-stage renal disease (ESRD; eCrCl <15 mL/min) who are not
receiving chronic hemodialysis; in patients on chronic
hemodialysis, on hemodialysis days, administer VEMLIDY after
completion of hemodialysis treatment. No data are available to make
dose recommendations in pediatric patients with renal
impairment.
- Hepatic Impairment: Not recommended in patients with
decompensated (Child-Pugh B or C) hepatic impairment.
Indication
VEMLIDY is indicated for the treatment of chronic hepatitis B
virus infection in adults and pediatric patients six years of age
and older and weighing at least 25 kg with compensated liver
disease.
About the 1092 Study
Study 1092 is an ongoing Phase 2 clinical trial that randomized
88 treatment-naïve and treatment-experienced patients with chronic
hepatitis B infection between the ages of 12 to less than 18 years
weighing at least 35 kg to receive either Vemlidy 25 mg (N=47) or
placebo (N=23) and 6 to less than 12 years weighing at least 25 kg
to receive either Vemlidy 25 mg (N = 12) or placebo (N=6) once
daily. The study met its primary endpoint of percentage of patients
with HBV DNA levels below 20 IU/mL at 24 weeks of therapy; overall,
19% (11/59) of patients treated with Vemlidy 25 mg achieved HBV DNA
< 20 IU/mL at Week 24 compared to 0% (0/23) of patients treated
with placebo. The overall percentage of patients with HBV DNA <
20 IU/mL progressively increased in the Vemlidy 25 mg group
relative to the Week 24 time point at both Week 48 (37% [22/59
subjects]) and Week 96 (61.0% [36/59 subjects]).
The overall median change from baseline in ALT values for the
Vemlidy and placebo-Vemlidy treatment groups, respectively, was
-39.5 U/L and -46.5 U/L at Week 96. At 96 weeks, ALT normalization
(AASLD criteria) was achieved for 54% of Vemlidy-treated patients
and 57% of patients who switched from placebo to Vemlidy. Serum ALT
is an enzyme used to monitor liver damage. Importantly, the mean
percent changes in bone mineral density from baseline to Week 24
were similar for Vemlidy-treated patients and placebo-treated
patients (1.6% (N=48) and 1.9% (N=23) for lumbar spine, and 1.9%
(N=50) and 2.0% (N=23) for whole body, respectively). At Week 24,
mean changes from baseline BMD Z-scores were 0.01 and -0.07 for the
lumbar spine, and -0.04 and -0.04 for whole body, for Vemlidy and
placebo groups, respectively.
About Hepatitis B
Hepatitis B (HBV) is a serious disease that attacks the liver
and can cause chronic (lifelong) infection, cirrhosis of the liver,
liver cancer, and death in up to a third of patients. Hepatitis B
is spread through infected blood or body fluids, sexual contact,
injection drug use, or perinatally from mother to child. Early
symptoms may include loss of appetite, fever, generalized aches and
pains, fatigue, itching, urticaria (hives), and joint pain. The
disease is often asymptomatic, which may lead to undiagnosed
individuals. Later symptoms may include nausea and vomiting,
halitosis (bad breath), dark brown urine, jaundice (yellowing of
the skin and eyes), and right-sided abdominal pain (especially with
external pressure or palpitation).
About Gilead Sciences in Liver
Disease
For more than 20 years, Gilead has sought to address some of the
biggest challenges in liver disease. The company has transformed
the trajectory of multiple liver diseases through a relentless
pursuit of innovation and pioneering access programs to bring
meaningful therapies to people around the world. More work is
required, and Gilead is committed to advancing innovative
therapeutics to address the most pressing unmet needs in liver
disease and overcoming barriers to better care.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades with the goal of creating a healthier world for all people.
The company is committed to advancing innovative medicines to
prevent and treat life-threatening diseases, including HIV, viral
hepatitis, COVID-19 and cancer. Gilead operates in more than 35
countries worldwide, with headquarters in Foster City,
California.
Forward-Looking
Statements
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 Gilead’s ability to initiate, progress or complete
clinical trials or studies within currently anticipated timelines
or at all, and the possibility of unfavorable results from ongoing
and additional clinical trials or studies, including those
involving Vemlidy; the risk that physicians may not see the
benefits of prescribing Vemlidy for the treatment of chronic HBV in
pediatric patients; and any assumptions underlying any of the
foregoing. These risks, uncertainties, and other factors could
cause actual results to differ materially from those referred to in
the forward-looking statements. All statements other than
statements of historical fact are statements that could be deemed
forward-looking statements. The reader is cautioned that any such
forward-looking statements are not guarantees of future performance
and is cautioned not to place undue reliance 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, 2023, 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 and
disclaims any intent to update any such forward-looking
statement.
U.S. Prescribing Information for Vemlidy,
including BOXED WARNINGS, is available at www.gilead.com
Vemlidy, Gilead, and the Gilead logo are
registered trademarks of Gilead Sciences, Inc., or its related
companies.
For more information about Gilead, 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240327502740/en/
Meaghan Smith, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Jul 2024 to Aug 2024
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Aug 2023 to Aug 2024