— 33 Presentations Evaluating Marketed and Investigational Compounds for Chronic Hepatitis B and Liver Fibrosis —
SAN FRANCISCO–(BUSINESS WIRE)–Nov. 14, 2015— Gilead Sciences, Inc. (Nasdaq:GILD) today announced it will present results from multiple studies of Viread® (tenofovir disoproxil fumarate, TDF) 300 mg for the treatment of chronic hepatitis B virus (HBV) infection, as well as new data regarding its investigational agents for HBV and nonviral liver diseases, including nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC), at The Liver Meeting 2015 taking place November 13-17 in San Francisco.
“The data accepted for presentation this week underscore Gilead’s ongoing commitment to advancing the care of people living with progressive liver diseases,” said Norbert Bischofberger, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “In addition to long-term data for Viread for patients with HBV, we are pleased to present data that advances our understanding of a number of new compounds in our pipeline that may have the potential to address unmet needs in HBV, as well as in NASH and PSC – two diseases for which there currently are no approved treatment options.”
Approved for chronic HBV in 2008, Viread is currently the most prescribed therapy for a disease that affects more than 350 million people worldwide. Five-year data presented this week support the durable antiviral efficacy and consistent safety and resistance profile of Viread (Posters #2004 and #1678). Data also demonstrate the investigational role of Viread in reducing perinatal transmission of HBV from highly viremic mothers (Oral #209).
Liver Disease Pipeline
Hepatitis B – TAF (tenofovir alafenamide), GS-9620 and GS-4774
TAF, a novel targeted prodrug of tenofovir, has demonstrated potent antiviral efficacy at a dose less than one-tenth that of Viread, as well as improvements in renal and bone safety laboratory markers in several Phase 3 studies for the treatment of HIV infection. Phase 3 results for TAF in patients with chronic HBV infection are expected by the end of 2015. Results being presented this week include a study demonstrating the antiviral activity of TAF against drug-resistant HBV isolates (Poster #2021).
The company will also present data highlighting two investigational compounds, the oral TLR-7 agonist GS-9620 and GS-4774, a therapeutic T-cell vaccine. These compounds are designed to stimulate the innate (GS-9620) and T-cell (GS-4774) responses to HBV, which may be important to cure patients with chronic HBV infection. Data presented include in vitro studies exploring the cellular mechanisms of antiviral response to GS-9620 (Oral #35 and Poster #2009), and results from a Phase 2 study of GS-4774 in virally-suppressed patients with chronic HBV (Poster #2015) and the associated immunologic and biologic responses observed in the trial (Poster #2052).
NASH and PSC
Gilead is investigating two compounds (simtuzumab and GS-4997) for their utility in treating NASH and PSC. NASH results from metabolic dysfunction that is associated with steatosis (fat within the liver), which leads to inflammation, hepatocellular injury and progressive fibrosis. It may also lead to cirrhosis and is expected to become the leading indication for liver transplantation by 2020. PSC is a disease characterized by inflammation and stricturing of the bile ducts. PSC eventually can also lead to cirrhosis and other complications, including bile duct cancer.
GS-4997, an apoptosis signal-regulating kinase (ASK1) inhibitor, is currently being evaluated in a Phase 2 study of patients with NASH and moderate to severe liver fibrosis. Simtuzumab, an anti-lysyl oxidase-like-2 (LOXL2) antibody, is being evaluated for the treatment of NASH and PSC in ongoing Phase 2b trials.
Three abstracts were accepted for poster presentations that characterized in animal models the effects of simtuzumab alone (Poster #1379), GS-4997 alone (Poster #1359), and the combination of simtuzumab and GS-4997 on fibrosis and portal hypertension (Poster #1367).
Nine abstracts were also accepted for presentation as posters that characterize the patient populations enrolled in the ongoing Phase 2b trials of simtuzumab in NASH and PSC, respectively. These included the baseline disease associations of serum LOXL2, histology and portal pressure in these patient populations (Posters #616, #624, #632, #737, #739, #1428, #1435, #2149 and #2239).
Further information about the clinical studies described above can be found at www.clinicaltrials.gov.
Abstracts for Gilead’s presentations can be accessed at http://www.aasld.org/sites/default/files/2015SupplementFULLTEXT.pdf
GS-4774, GS-4997, GS-9620, simtuzumab and TAF are investigational products and have not been determined to be safe or efficacious.
Important Safety Information About Viread for Chronic Hepatitis B
BOXED WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including Viread, in combination with other antiretrovirals
Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. 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 Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted
Warnings and precautions
New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of Viread. In all patients, assess estimated creatinine clearance (CrCl) prior to initiating and during therapy. In patients at risk for renal dysfunction, including those who previously experienced renal events while receiving adefovir dipivoxil, additionally monitor serum phosphorus, urine glucose, and urine protein. In patients with CrCl <50 mL/min, adjust dosing interval and closely monitor renal function. Avoid concurrent or recent use with a nephrotoxic agent. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in HIV-infected patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients. Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function.
Coadministration with other products:
– Do not use in combination with other products containing tenofovir disoproxil fumarate
– Do not administer in combination with adefovir dipivoxil
Patients coinfected with HIV-1 and HBV: Due to the risk of development of HIV-1 resistance, Viread should only be used in HIV-1 and HBV coinfected patients as part of an appropriate antiretroviral combination regimen. HIV-1 antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread.
Bone effects: Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in patients treated with Viread. Consider assessment of BMD in adult and pediatric patients who have a history of pathologic bone fracture or other risk factors for bone loss. In a clinical trial conducted in pediatric subjects 12 to <18 years of age with chronic hepatitis B, total body BMD gain was less in Viread -treated subjects as compared to the control group. In patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms, hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered
In HBV-infected subjects with compensated liver disease: Most common adverse reaction (all grades) was nausea (9%). Other treatment-emergent adverse reactions reported in >5% of patients treated with Viread included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain, and skin rash
In HBV-infected subjects with decompensated liver disease: Most common adverse reactions (all grades) reported in ≥10% of patients treated with Viread were abdominal pain (22%), nausea (20%), insomnia (18%), pruritus (16%), vomiting (13%), dizziness (13%), and pyrexia (11%)
Didanosine: Coadministration increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (e.g., pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In patients weighing >60 kg, the didanosine dose should be reduced to 250 mg once daily when it is coadministered with Viread and in patients weighing <60kg, the didanosine dose should be reduced to 200 mg once daily when coadministered with Viread
HIV-1 protease inhibitors: Coadministration decreases atazanavir concentrations and increases tenofovir concentrations; use atazanavir given with ritonavir. Coadministration of Viread with atazanavir and ritonavir, darunavir and ritonavir, or lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity
Drugs affecting renal function: Coadministration of Viread with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir
Dosage and Administration
Recommended dose, in adults and pediatric patients ≥12 years of age (≥35 kg), for the treatment of chronic hepatitis B: one 300 mg tablet, once daily, taken orally, without regard to food
In the treatment of chronic hepatitis B, the optimal duration of treatment is unknown
Safety and efficacy in pediatric patients <12 years of age or weighing <35kg with chronic hepatitis B have not been established
The dosing interval of VIREAD should be adjusted and renal function closely monitored in patients with baseline creatinine clearance (CrCL) <50 mL/min. For patients with CrCL 30-49mL/min, the interval is every 48 hours and with CrCL 10-29mL/min, the interval is every 72-96 hours. For hemodialysis patients, the interval is every 7 days or after a total of approximately 12 hours of dialysis. Consult the full Prescribing Information for additional information.
The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients
No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein should be performed in these patients
No data are available to make dose recommendations in pediatric patients with renal impairment
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.
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 these studies and other ongoing and subsequent clinical trials involving GS-4774, GS-4997, GS-9620, simtuzumab, TAF and Viread. 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 September 30, 2015, 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 WARNING for Viread is available at www.gilead.com.
Viread is a registered trademark of Gilead Sciences, Inc.
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.
Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)
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