Gilead’s Odefsey® (Emtricitabine, Rilpivirine, Tenofovir Alafenamide) Meets Primary 48-Week Objective in Two Phase 3b Studies

FOSTER CITY, Calif.–(BUSINESS WIRE)–Gilead Sciences, Inc. (Nasdaq:GILD) today announced that two Phase 3b
switch studies evaluating Odefsey^® (emtricitabine
200mg/rilpivirine 25mg/tenofovir alafenamide 25mg) for the treatment of
HIV-1 infection met their primary objectives. The ongoing studies were
designed to explore the efficacy and safety of Odefsey among
virologically suppressed adult patients switching from the tenofovir
disoproxil fumarate (TDF)-based regimens Complera^®
(emtricitabine 200mg/rilpivirine 25mg/tenofovir disoproxil fumarate
300mg) (Study 1216) or Atripla^® (efavirenz
600mg/emtricitabine 200mg/tenofovir disoproxil fumarate 300mg) (Study
1160). Odefsey combines Gilead’s emtricitabine and tenofovir alafenamide
with rilpivirine, marketed by Janssen Sciences Ireland UC, one of the
Janssen Pharmaceutical Companies of Johnson & Johnson.
Odefsey maintained similar rates of virologic suppression as the
TDF-based regimens in both studies based on the proportion of patients
with HIV-1 RNA levels (viral load) <50 copies/mL. At Week 48, virologic
suppression was maintained in 94 percent of patients taking Odefsey and
in 94 percent of patients taking Complera in Study 1216 (difference:
-0.3 percent; 95 percent CI: -4.2 percent to +3.7 percent), and in 90
percent of patients taking Odefsey versus 92 percent of patients taking
Atripla in Study 1160 (difference: -2.0 percent; 95 percent CI: -5.9
percent to +1.8 percent).
Compared to the TDF-based regimens, Odefsey demonstrated statistically
significant improvements in bone mineral density (BMD) at the hip and
spine (p<0.001) in both studies. Additionally, improvements in total and
tubular proteinuria statistically favored Odefsey in both studies
(p<0.001). Study regimens were generally well tolerated, and general
safety and discontinuation rates due to adverse events were comparable
in the two studies. The most commonly reported adverse events for
Odefsey included upper respiratory tract infection, diarrhea,
nasopharyngitis, cough and headache. Gilead plans to submit these data
for presentation at scientific conferences in 2016.
“As people are living longer with HIV, there is an increasing need for
safe and tolerable treatment options to help address the long-term
health needs of people living with HIV,” said Norbert Bischofberger,
PhD, Executive Vice President, Research and Development and Chief
Scientific Officer, Gilead Sciences. “Results from these two studies
support the efficacy, as well as the renal and bone safety profile, of
Odefsey as a new treatment option for virologically suppressed patients.”
Odefsey was approved in the United States on March 1, 2016, and is
indicated as a complete regimen for the treatment of HIV-1 infection in
patients 12 years of age and older who have no antiretroviral treatment
history and HIV-1 RNA levels ≤100,000 copies/mL. Odefsey is also
indicated as replacement for a stable antiretroviral regimen in those
who are virologically suppressed (HIV-1 RNA <50 copies/mL) for at least
six months with no history of treatment failure and no known resistance
to the individual components of Odefsey. No dosage adjustment of Odefsey
is required in patients with estimated creatinine clearance ≥30 mL per
minute.
Odefsey has a boxed warning in its product label regarding the risks of
lactic acidosis/severe hepatomegaly with steatosis, and post treatment
acute exacerbation of hepatitis B. See below for important safety
information.
About Studies 1216 and 1160
Study 1216 is a Phase 3b, randomized, double-blind, multicenter study
among 630 virologically suppressed adults (HIV-1 RNA levels <50
copies/mL) on a stable regimen of Complera for ≥ six consecutive months.
Patients were randomized 1:1 to either maintain their Complera regimen
or switch to Odefsey. Study 1160 is a Phase 3b, randomized,
double-blind, multicenter study among 875 virologically suppressed
adults (HIV-1 RNA levels <50 copies/mL) on a stable regimen of Atripla
for ≥ six consecutive months. Patients were randomized 1:1 to either
maintain their Atripla regimen or switch to Odefsey. The studies will
follow patients for 96 weeks after randomization.
The studies are ongoing. The primary objective of each study is to
evaluate the efficacy of switching from Complera or Atripla to Odefsey
in HIV-1 positive subjects who are virologically suppressed as
determined by the proportion of subjects with HIV-1 RNA <50 copies/mL at
Week 48 as defined by the FDA snapshot algorithm. The secondary
objectives are to evaluate the bone safety of the regimens by the
percent change from baseline in hip and spine BMD at Week 48 and Week
96, to evaluate the safety and tolerability of the treatment arms
through Week 48 and to evaluate the efficacy, safety and tolerability of
the treatment arms through Week 96.
Additional information about the studies can be found at www.clinicaltrials.gov.
Important U.S. Safety Information for Odefsey
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and
POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

• Lactic acidosis and severe hepatomegaly with steatosis, including
  fatal cases, have been reported with the use of nucleoside analogs in
  combination with other antiretrovirals.
• Odefsey is not approved for the treatment of chronic hepatitis B
  virus (HBV) infection, and the safety and efficacy of Odefsey have not
  been established in patients coinfected with HIV-1 and HBV. Severe
  acute exacerbations of hepatitis B have been reported in patients who
  are coinfected with HIV-1 and HBV and have discontinued products
  containing emtricitabine and/or tenofovir disoproxil fumarate (TDF),
  and may occur with discontinuation of Odefsey. Hepatic function should
  be monitored closely with both clinical and laboratory follow-up for
  at least several months in patients who are coinfected with HIV-1 and
  HBV and discontinue Odefsey. If appropriate, initiation of
  anti-hepatitis B therapy may be warranted.

Contraindications

• Coadministration: Do not use with drugs that induce CYP3A or
  increase gastric pH as this may lead to loss of efficacy and possible
  resistance to Odefsey or the NNRTI class. Do not use with
  carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin,
  rifapentine, proton pump inhibitors (e.g., dexlansoprazole,
  esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole),
  systemic dexamethasone (>1 dose) and St. John’s wort.

Warnings and precautions

• Skin and hypersensitivity reactions: Severe skin and
  hypersensitivity reactions have been reported with the use of
  rilpivirine-containing regimens, including cases of Drug Reaction with
  Eosinophilia and Systemic Symptoms (DRESS). In rilpivirine clinical
  trials, most rashes were Grades 1-2 and occurred in the first 4-6
  weeks of treatment; Grades 2-4 rash occurred in 1% of subjects.
  Discontinue Odefsey immediately if severe skin or hypersensitivity
  reactions occur, including severe rash or rash accompanied by fever,
  blisters, mucosal involvement, conjunctivitis, facial edema,
  angioedema, hepatitis or eosinophilia. Monitor clinical status
  including laboratory parameters and initiate appropriate therapy.
• Loss of virologic response due to drug interactions: See
  Contraindications and Drug Interactions sections. Consider the
  potential for drug interactions prior to and during Odefsey therapy
  and monitor for adverse reactions.
• Prolongation of QTc interval: Rilpivirine doses 3 and 12 times
  higher than the recommended dose can prolong the QTc interval.
  Consider alternatives to Odefsey in patients at higher risk for
  Torsade de Pointes or when coadministered with a drug with known risk
  of Torsade de Pointes.
• Depressive disorders: Evaluate patients with severe depressive
  symptoms to assess if symptoms are due to Odefsey and if the risks of
  continued treatment outweigh the benefits. In rilpivirine adult
  clinical trials (N=686), the incidence of depressive disorders was 9%,
  Grades 3-4 depressive disorders was 1%, discontinuation due to
  depressive disorders was 1%, and suicidal ideation and suicide attempt
  was reported in 4 and 2 subjects, respectively. In a rilpivirine
  adolescent clinical trial (N=36), the incidence of depressive
  disorders was 19%, Grades 3-4 depressive disorders was 6%, and
  suicidal ideation and suicide attempt were reported in 1 subject.
• Hepatotoxicity: Hepatic adverse eventshave been
  reported, including cases of hepatic toxicity, in patients without
  pre-existing hepatic disease or other identifiable risk factors. In
  patients with hepatic abnormalities (e.g., hepatitis, elevated
  liver-associated tests), order laboratory tests before starting
  treatment and monitor for hepatotoxicity during treatment; consider
  testing and monitoring in all patients.
• Fat redistribution or accumulation has been observed in
  patients receiving antiretroviral therapy.
• Immune reconstitution syndrome, including the occurrence of
  autoimmune disorders with variable time to onset, has been reported.
• New onset or worsening renal impairment: Cases of acute renal
  failure and Fanconi syndrome have been reported with the use of
  tenofovir prodrugs. In clinical trials of emtricitabine and tenofovir
  alafenamide with elvitegravir and cobicistat, there have been no cases
  of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not
  initiate Odefsey 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 Odefsey in patients who
  develop clinically significant decreases in renal function or evidence
  of Fanconi syndrome.
  Renal monitoring: In all patients,
  monitor CrCl, urine glucose, and urine protein prior to initiating and
  during therapy. In patients with chronic kidney disease, additionally
  monitor serum phosphorus.

• Bone loss and mineralization defects: Decreases in bone mineral
  density (BMD) have been reported with the use of tenofovir prodrugs.
  Consider monitoring BMD in patients with a history of pathologic
  fracture or risk factors for bone loss. Mineralization defects,
  including osteomalacia associated with PRT, have been reported with
  the use of TDF-containing products.

Adverse reactions

• Most common adverse reactions with rilpivirine (incidence ≥2%,
  Grades 2-4) are depressive disorders (2%), insomnia (2%) and headache
  (2%); and with emtricitabine and tenofovir alafenamide (incidence
  ≥10%, all grades) is nausea (10%).

Drug interactions

• Prescribing information: Consult the full prescribing
  information for Odefsey for more information on Contraindications,
  Warnings, and potentially significant drug interactions, including
  clinical comments.
• Metabolism: Drugs that induce CYP3A or P-gp and drugs that
  increase gastric pH can decrease the concentrations of components of
  Odefsey. Drugs that inhibit CYP3A or P-gp can increase the
  concentrations of components of Odefsey.
• QT prolonging drugs: Consider alternatives to Odefsey in
  patients taking a drug with known risk of Torsade de Pointes.
• Drugs affecting renal function: Coadministration of Odefsey
  with drugs that reduce renal function or compete for active tubular
  secretion may increase concentrations of emtricitabine and tenofovir
  and the risk of adverse reactions.

Dosage and administration

• Dosage: Patients 12 years and older (≥35 kg): 1 tablet taken
  orally once daily with a meal.
• Renal impairment: Not recommended in patients with CrCl <30
  mL/min.
• Testing prior to initiation: Test patients for HBV infection
  and assess CrCl, urine glucose and urine protein.
• Testing after initiation: In virologically-suppressed patients,
  additional monitoring of HIV-1 RNA and regimen tolerability is
  recommended.

Pregnancy and lactation

• Pregnancy: There are insufficient data on the use of Odefsey
  during pregnancy. In animal studies, no adverse developmental effects
  were observed with the components of Odefsey. An Antiretroviral
  Pregnancy Registry has been established.
• Lactation: Women infected with HIV-1 should be instructed not
  to breastfeed, due to the potential for HIV-1 transmission.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company’s mission is to advance the care of patients suffering
from life-threatening diseases. Gilead has operations in more than 30
countries worldwide, with headquarters in Foster City, California.
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 risk
that physicians may not see the benefits of prescribing Odefsey. 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 ended March 31, 2016, 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, including BOXED WARNINGS,
for Atripla, Complera and Odefsey
are available at www.gilead.com.

Atripla, Complera and Odefsey are registered 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.