With hopes of soon filing a new drug application for Ampligen, Hemispherx Biopharma Inc. presented new Phase III data that support the drug's use in chronic fatigue syndrome.

At the 44th annual Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, the Philadelphia-based company highlighted data from its pivotal Phase III trial of Ampligen in CFS. The data showed increases in exercise capacity with Ampligen vs. placebo, which were correlated with an improved ability to use oxygen, or so-called maximum oxygen consumption (VO₂max).

VO₂max has been shown to be decreased in people with CFS. Additional data on subset analyses showed that both cohorts improved exercise capacity substantially. The new data, following 40 weeks of treatment with Ampligen, also showed significant correlations between improvements in treadmill exercise duration and Karnofsky Performance Score.

The company expects the data to support the upcoming new drug application filing.

The Phase III trial focused on the efficacy and safety of Ampligen, given at the 400-mg dose twice weekly vs. placebo in patients with severely debilitating CFS.

It randomized 234 patients at 12 centers across the U.S. The primary endpoint was improved physical performance as measured by Treadmill Exercise Tolerance Testing (ETT): Duration. With ETT, significance is determined by at least a 6.5 percent increase in mean exercise duration from baseline to week 40.

Patients receiving Ampligen for 40 weeks improved exercise treadmill performance 21.2 percent vs. 5.1 percent in the placebo group.

Hemispherx released initial data from the pivotal trial in May. (See BioWorld Today, May 4, 2004.)

CFS affects more than 500,000 people in the U.S. and a similar number in Europe each year. The Centers for Disease Control and Prevention set the annual economic cost of CFS in the U.S. at more than $9 billion.

Ampligen, a double-stranded RNA drug, is in two Phase IIb trials for other chronic diseases. The FDA has granted Ampligen orphan drug status.

In other news from ICAAC:

• Abbott Laboratories, of Abbott Park, Ill., said study data presented showed no primary protease inhibitor resistance in antiretroviral-na ve patients taking a Kaletra-based regimen through six years of therapy. Data also showed the majority of patients taking Kaletra in combination with other antiretroviral agents maintained an undetectable viral load of less than 50 copies per milliliter. Kaletra generally was well tolerated through the 300 weeks.

• ActivBiotics Inc., of Lexington, Mass., said rifalazil in a Phase II trial to treat acute non-gonococcal urethritis met all of its primary endpoints. The trial was conducted at 11 sites in the U.S. and enrolled 170 men diagnosed with acute NGU and screened for Chlamydia trachomatis. All patients received a single dose of either rifalazil or azithromycin. Primary endpoints were clinical cure, microbiologic cure, safety and a composite endpoint of therapeutic cure.

• Dynavax Technologies Inc., of Berkeley, Calif., said data from a randomized, double-blind Phase II trial of its prophylactic hepatitis B virus vaccine showed superior results compared to London-based GlaxoSmithKline plc's Engerix-B vaccine. Protective antibody responses were achieved faster and maintained longer with Dynavax's HBV vaccine than with Engerix-B. Dynavax's vaccine combines its immunostimulatory sequence co-administered with HBV surface antigen.

• Ecopia BioSciences Inc., of Montreal, presented data on ECO-0501 in three posters showing the product could be an effective antibacterial agent to treat antibiotic-resistant infections commonly acquired in hospital settings. The data demonstrated that the antibacterial agent kills bacteria by exerting action through cell-membrane disruption. In addition to its potency, ECO-0501 has demonstrated a good safety profile and therapeutic window.

• Elusys Therapeutics Inc., of Pine Brook, N.J., presented data on its Heteropolymer (HP) antibody technology. The Elusys S. aureus-HP consists of an antibody to CR1, a receptor on red blood cells, crosslinked to an antibody to Staphylococcus aureus. Elusys evaluated the ability of the S. aureus-HP to prevent infection in mice injected with the bacteria, and compared its ability to the single S. aureus monoclonal antibody alone. The study found that the mice given the Elusys HP were protected against a lethal injection of S. aureus strains, including methicillin-resistant S. aureus, and all survived. In comparison, none of the mice given a much higher dose of the single monoclonal antibody survived.

• Gilead Sciences Inc., of Foster City, Calif., presented 24-week data from an ongoing clinical trial that suggest treatment-na ve patients with HIV who receive a once-a-day regimen of Viread, Emtriva and efavirenz had fewer adverse event-related study discontinuations (3 percent), compared to those who received twice-daily Combivir and once-daily efavirenz (9 percent). The study is an open-label Phase III trial in more than 500 patients in the U.S. and Europe. The FDA recently granted accelerated approval of Truvada, a fixed-dose tablet containing Viread and Emtriva, to be taken once daily in combination with other antiretrovirals. A separate presentation at ICAAC focused on the drug, Tamiflu (oseltamivir), which is co-developed by Gilead and Hoffmann-La Roche Inc., of Nutley, N.J. New data confirm that oseltamivir, an oral neuraminidase inhibitor, is effective against the human H5N1 and avian H5N1 influenza virus, which is circulating in Vietnam and Thailand. Tamiflu also showed its ability to reduce the risk of pneumonia in patients diagnosed with flu in a retrospective cohort study of more than 70,000 Americans. Reduction in pneumonia was most pronounced in higher-risk groups, with a 59 percent decrease in older Americans, and a 66 percent decrease in children aged 12 and younger.

• Idenix Pharmaceuticals Inc., of Cambridge, Mass., presented data on telbivudine and valtorcitabine, candidates for hepatitis B virus infection being developed in collaboration with Basel, Switzerland-based Novartis Pharma AG. Data from the one-year Phase IIb trial for telbivudine showed that patients demonstrated faster and more profound first-phase clearance (within two weeks) as well as improved second-phase clearance (week three to week 12), compared to lamivudine alone. A separate presentation made at the American Association for the Study of Liver Diseases meeting evaluated virologic data from the four-week Phase I dose-escalation trial of telbivudine and confirmed those results. Telbivudine is in a Phase III head-to-head study against lamivudine. Also at AASLD, the company reported valtorcitabine results that support development in combination with telbivudine for hepatitis B patients unable to achieve optimal therapeutic response with a single agent.

• Incyte Corp., of Wilmington, Del., said patients with HIV who were failing antiretroviral therapy showed a reduction in viral load following treatment with Reverset, a nucleoside-analogue reverse transcriptase inhibitor. The company reported data from a fourth cohort of 10 treatment-experienced patients in a Phase IIa trial conducted jointly by Incyte and Pharmasset Inc. Seven of the eight patients treated with Reverset demonstrated a clinically significant reduction in viral load. Data also showed that six subjects receiving or failing therapy with 3TC (Epivir), and five subjects receiving or failing treatment with tenofovir (Viread) achieved a mean viral load reduction of at least 0.7 log copies/mL following treatment with Reverset.

• Inhibitex Inc., of Atlanta, presented positive results from its preclinical studies and Phase I trial of Aurexis, which is being developed as a first-line therapy, in combination with antibiotics, for serious Staphylococcus aureus infections. Data from preclinical animal studies demonstrated that Aurexis provided significant prophylactic and therapeutic activity against those infections, including methicillin-resistant S. aureus. The company has enrolled 51 out of 60 patients in an ongoing Phase II trial in patients with S. aureus bloodstream infections. Data are expected in the second quarter of 2005.

• Trimeris Inc., of Durham, N.C., and Hoffmann-La Roche Inc., of Nutley, N.J., said the earlier use of Fuzeon (enfuvirtide) in treatment-experienced HIV patients results in better treatment outcomes and preserves future drug options. A new analysis found that 33 percent of patients who did not receive Fuzeon in their regimen at the beginning of the studies developed resistance to at least one active treatment option. But only 13 percent of those who began with a Fuzeon-based regimen experienced loss of at least one option after 48 weeks of virological failure.

• Vertex Pharmaceuticals Inc., of Cambridge, Mass., and London-based GlaxoSmithKline plc reported results of pharmacokinetic comparisons between the protease inhibitors Lexiva (fosamprenavir calcium) plus ritonavir (RTV) and Agenerase (amprenavir) plus RTV. Those taking Lexiva plus RTV experienced fewer gastrointestinal effects, skin rashes and neurological adverse events than patients taking Agenerase plus RTV. Vertex and GSK co-discovered Lexiva, which was approved in combination with other antiretroviral medications by the FDA for HIV in October 2003. It has been shown to be similar in efficacy to Agenerase, but offers some dosing benefits. Lexiva is dosed twice daily and has no food or water restrictions, whereas Agenerase requires dosing of eight capsules twice a day and should not be taken with fatty foods. Researchers also presented data showing increases in HDL cholesterol in HIV patients on regimens containing Lexiva. Minimal changes were seen in total cholesterol/HDL-C ratios.

• Vicuron Pharmaceuticals Inc., of King of Prussia, Pa., said data demonstrated dalbavancin's potency against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Separately, studies on anidulafungin show its in vitro activity is more potent than fluconazole against Candida albicans biofilms, which are difficult-to-treat hospital-acquired infections. It also has demonstrated efficacy against azole-refractory mucosal candidiasis. Vicuron also said that preclinical research supports further development of VIC-5555, its lead lincosamide. The next-generation clindamycin antibiotic has demonstrated improved in vivo efficacy, potency and dosing.