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FOSTER CITY, Calif. — Gilead Sciences, Inc. (Nasdaq:GILD) today announced that Study 103, a Phase III clinical trial evaluating the company’s once-daily anti-HIV drug Viread([R]) (tenofovir disoproxil fumarate or tenofovir DF) 300 mg as a potential treatment for chronic hepatitis B virus (HBV) infection, met its primary efficacy endpoint. The data show that Viread is non-inferior to the company’s once-daily antiviral drug Hepsera([R]) (adefovir dipivoxil) among patients with "e" antigen (HBeAg)-positive chronic hepatitis B. The primary efficacy endpoint, the proportion of patients with a complete response at week 48, was defined by serum HBV DNA levels below 400 copies/mL and histologic improvement characterized by at least a two point reduction in the Knodell necroinflammatory score (a measure of necro-inflammation - an inflammatory process in the liver including or leading to death of liver cells) with no concurrent worsening of fibrosis (scarring of liver tissue).

At 48 weeks, 66.5 percent of patients in the Viread arm (n=176) had a complete response compared to 12.2 percent in the Hepsera arm (n=90; p<0.001). The most commonly observed treatment-emergent adverse events of moderate intensity or higher were abdominal pain, back pain, headache, respiratory infections and transaminase elevations. The incidence of these events was comparable between the Viread and Hepsera arms of the study. In addition, the most frequently observed grade 3 or 4 laboratory abnormalities were elevations in transaminase and serum amylase and were comparable between the two arms. Full study results will be submitted for presentation at an upcoming scientific meeting.

Study 103 is the second of two Phase III pivotal studies evaluating the efficacy, safety and tolerability of Viread for the treatment of chronic hepatitis B to have met its primary efficacy endpoint. Earlier this month, the company announced that the first study (Study 102) met its primary 48-week efficacy endpoint showing that Viread is non-inferior to Hepsera among patients with HBeAg-negative/anti-HBe positive (presumed pre-core mutant) chronic hepatitis B.

"The preliminary data observed in both Phase III trials evaluating Viread as a potential treatment option for chronic hepatitis B are very encouraging," said Franck Rousseau, MD, Vice President, Clinical Research, Gilead Sciences. "We look forward to reviewing these data with regulatory authorities and are working quickly to file a New Drug Application in the United States and Marketing Authorisation Application in Europe in the fourth quarter of this year."

The active ingredient in Viread, tenofovir DF, is currently the most prescribed molecule in the United States for combination HIV therapy. Viread received approval as an anti-HIV medication from the U.S. Food and Drug Administration (FDA) in October 2001 and from the European Commission in February 2002. Viread is not approved as a treatment for chronic hepatitis B, and data from this analysis have not been reviewed by the FDA.

Study Design

Study 103 is a multi-center, randomized, double-blind Phase III clinical trial that compares the efficacy, safety and tolerability of Viread and Hepsera over 48 weeks among patients with HBeAg-positive chronic hepatitis B. Two hundred and sixty-six patients were randomized in a 2:1 ratio to receive either Viread (300 mg once daily; n=176) or Hepsera (10 mg once daily; n=90).

About Viread (tenofovir disoproxil fumarate)

In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Viread should not be used in combination with the fixed-dose combination products Truvada([R]) or Atripla([TM]) because they already contain Viread.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Viread is not approved for the treatment of chronic hepatitis B and the safety and efficacy of Viread have not been established in patients coinfected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV and HBV and discontinue Viread. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported in association with the use of Viread. It is recommended that creatinine clearance be calculated in all patients prior to initiating therapy with Viread and as clinically appropriate during therapy. Coadministration of Viread and didanosine should be undertaken with caution. Patients should be monitored closely for didanosine-associated adverse events, and didanosine should be discontinued if these occur. Patients on atazanavir and lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events, and Viread should be discontinued if these occur. When co-administered with Viread, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.

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The failure of the Mississippi Department of Health (MDH) to provide timely and accurate information about the number of West Nile virus (WNV) cases in Mississippi could have reduced the impetus to deal with the problem, said Sen. Alan Nunnelee, chairman ofthe Senate Public Health & Welfare Committee, who held 2006 hearings into problems at the MDH.

“There was significant underreporting of West Nile Virus,” Nunnelee said. “How that affects the health of most Mississippians is that we know West Nile is a mosquito-borne virus. We live in the Deep South, and mosquitoes are bad in the summertime. When the statistics are significantly underreported, it impacts local governments in the amount of resources they would dedicate to mosquito eradication. It also alerts physicians when patient presents themselves with symptoms that might be consistent with West Nile Virus. It goes way up the radar screen. That is just one aspect.”

The MDH has corrected the problems with WNV reporting, says Carol Jones, a spokesperson for MDH.

“We are getting out the information as quickly as we get it,” Jones said.

In both 2006 and now again in 2007, Mississippi was the first state in the union to report a WNV case. So far in 2007, there have been five reported cases of WNV and one death in Mississippi, according Dr. Lovetta Brown, interim state epidemiologist for MDH. There has been one case in each of five counties: Madison, Scott, Lawrence, Warren and Walthall counties.

“We just have to be really careful because West Nile is here,” Brown said. “It is too early to tell if it is as bad as last year. We have launched campaigns in areas where we have had cases and have also distributed funding to many of the rural counties that were impacted by Katrina so these communities can do more mosquito abating procedures. Those programs, if done properly, are very instrumental in decreasing the cases of West Nile, and that is why we provided funding to the counties that were impacted by Katrina.”

Running the numbers

WNV claimed 14 lives in Mississippi in 2006. There were 184 cases reported in 2006 with the largest number, 30, in Forrest County. That gave the region including Forrest County the highest WNV rate in the state at approximately 21 cases per 100,000 population. There were also 20 cases in Hinds County, 18 in Rankin County and 12 in Harrison County.

The cases reported in 2006 were the highest since 2002 when 193 cases were reported statewide. There were 83 cases and two deaths reported in 2003, and 52 cases and four deaths reported in 2004. There were 70 cases of WNV and six deaths in 2005.

Dr. Ralph Kahler, infectious disease specialist at the Hattiesburg Clinic, said it appears that mosquito-spraying programs in the area have helped prevent the spread of WNV. In 2006 after local authorities learned of the high number of WNV cases, prevention efforts were ramped up. Kahler said the hearings in Jackson did serve to increase awareness of the problem and the response by the local governments.

Knowledge of the presence of the disease also led to increased awareness by health professionals. But Kahler doesn’t think that there were more cases reported in Hattiesburg than other areas simply because of increased awareness.

“Certainly after the first few cases, everyone had a higher index of suspicion,” Kahler said. “But I really do think we had more serious cases last year than in years past. That is the first time it has happened. We don’t know if it is some kind of post-Katrina hurricane aftermath or exactly what. But when we finally did recognize the magnitude of the problem, the spraying programs for mosquitoes got in high gear and it kind of trailed off after that. In years past the Jackson area has been a bit of the leader, but last year we had a profound jump in our cases. The flurry of cases seemed to come in late June and early July. Probably half of our cases came the first month.”

Reporting of WNV is complicated by the fact that 80% of the people who have West Nile never know that they have it because it doesn’t develop into a serious illness. Kahler said approximately 20% of victims have a flu-like illness with fever, aches, rash, some eye pain and sometimes headaches. Approximately 1% will have neurological manifestations of meningitis or encephalitis, and a small percentage of those will have permanent neurological deficit in the form of paralysis or death.

“Death is mostly in the older or more immuno-compromised groups,” Kahler said. “Most of the deaths I have personally seen have been in people over 65. As far as a convalescent period, it may take people months to get back tonormal where they aren’t having aches, weakness and difficulty concentrating.”

Residents and business owners need to do their part to help combat the problem. Kahler recommends going around yards and removing anything holding standing water that can serve as breeding areas for mosquitoes. Empty children’s wading pools when not in use, and replace the water weekly in pet dishes and bird baths. If outside and fairly sedentary, he recommends protective clothing and/or a mosquito repellent.

Information provided by: Findarticles.com