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Romark Laboratories, L.C. Announces Clinical Trial Results for New Influenza Drug Presented at IDSA Meeting 2011  
10/21/2011 12:42:57 PM

TAMPA, Fla., Oct. 21, 2011 /PRNewswire/ -- Romark Laboratories announced that results of a large Phase 2B-3 US clinical trial of its new flu drug, NT-300 (nitazoxanide), will be presented as an oral late-breaking communication at the 49th Annual Meeting of the Infectious Diseases Society of America (IDSA) being held in Boston, October 20-23, 2011.

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The clinical trial enrolled 624 patients at 74 outpatient primary care centers throughout the United States during the 2010-2011 flu season. The trial achieved its primary endpoint showing that influenza-infected patients treated with NT-300 administered 600 mg twice daily for five days experienced statistically significant reduction in time from beginning treatment to alleviation of flu symptoms compared to influenza-infected patients receiving the placebo (P=0.008).

Approximately half of the influenza-infected patients enrolled in the US clinical trial were infected with influenza A subtype H1N1 ("swine flu") with approximately 30% being infected with influenza B and 20% with influenza A subtype H3N2.

"These data are encouraging," said Jean-Francois Rossignol, M.D., Ph.D., Chairman and Chief Science Officer of Romark. "We currently have only two drugs to treat influenza, both neuraminidase inhibitors, and resistance is a major concern. There is an urgent need for a new drug with a different mechanism of action for treating influenza."

Data from two other Phase 2 clinical trials, including one clinical trial in children down to 12 months of age, and laboratory studies of the drug's activity against influenza viruses will also be presented at the IDSA meeting. In total, four different communications will be presented. The meeting is attended by infectious disease physicians, scientists and public health personnel from the United States and around the world.

Romark plans to initiate another Phase 3 clinical trial of NT-300 during the coming flu season and to seek FDA approval to market NT-300 for treatment of acute uncomplicated influenza. The company also plans to develop NT-300 for prevention of influenza and for treatment of influenza in special populations (e.g., pediatric patients under 12 years of age, geriatric patients and patients with severe illness or underlying medical conditions).

NT-300, an investigational new drug in the United States, is an oral controlled release tablet that contains 300 mg of nitazoxanide (NTZ) as active ingredient. NTZ is the first of a new class of small molecule immunomodulatory drugs called thiazolides. Romark is using this new class of drugs as a technology platform for developing new drugs for treating a broad range of viral diseases and cancers. NT-300 is undergoing clinical development for treatment of influenza.

There are presently only two classes of drugs approved by the FDA for treating flu: the neuraminidase inhibitors, oral Tamiflu® (oseltamivir) and inhaled Relenza® (zanamivir), and the older M2 inhibitors, amantadine and rimantadine. The M2 inhibitors are no longer effective against circulating influenza strains. Resistance to the neuraminidase inhibitors has been observed, and during the 2008-2009 flu season, approximately 99% of circulating influenza A H1N1 strains were resistant to oseltamivir (Tamiflu®), the only oral drug for treating influenza. There has not been a new class of drugs approved for treating influenza since Tamiflu® and Relenza® were approved by FDA in 1999.

Data from laboratory studies of NTZ to be presented at the IDSA meeting have shown that NTZ is active against a broad range of influenza viruses including oseltamivir- and amantadine-resistant strains. Laboratory studies designed to create or select for influenza strains resistant to NTZ could not identify viruses resistance to NTZ in cell cultures. Other studies showed that NTZ was also active in cell culture against other respiratory viruses that may cause flu-like symptoms including coronavirus and parainfluenza virus. Finally, laboratory studies to be communicated at the IDSA meeting have shown strong synergistic activity of combinations of NTZ and oseltamivir (the active ingredient in Tamiflu®) against influenza viruses in cell cultures.

The four communications to be presented at the IDSA meeting are:

1. Randomized, Double-Blind, Pilot Study of Nitazoxanide (NTZ) Versus Placebo (PCB) for the Treatment of Symptoms Associated with Viral Respiratory Infection (VRI) in Adults and Adolescents. Nicolas Lopez-Chegne, Luis-Martin Julcamoro, Maria Carrion, Jean-Francois Rossignol, Matthew Bardin. Presentation Number 142, Session 37, Oral Abstract Session: Clinical Virology and Treatment. Friday, October 21, 2011, 9:45 AM.

2. Nitazoxanide, a Novel Potential Anti-Influenza Drug, Acting in Synergism with Neuraminidase Inhibitors.Giuseppe Belardo, Simone La Frazia, Orlando Cenciarelli, Stefania Carta, Jean-Francois Rossignol, M. Gabriella Santoro. Presentation Number 1181, Session 149, Poster Abstract Session: New Approaches to Anti-viral Therapy. Saturday, October 22, 2011, 1:45 PM.

3. Randomized, Double-Blind, Pilot Study of Nitazoxanide (NTZ) Versus Placebo (PCB) for the Treatment of Symptoms Associated with Viral Respiratory Infection (VRI) in Children. Nicolas Lopez-Chegne, Luis-Martin Julcamoro, Maria Carrion, Jean-Francois Rossignol, Matthew Bardin. Presentation Number 1341, Session 174, Oral Abstract Session: Respiratory Infections in Children. Saturday, October 22, 2011, 2:00 PM.

4. A Randomized, Double-Blind, Placebo (PCB) Controlled Study of Nitazoxanide (NTZ) in Adults and Adolescents with Acute Uncomplicated Influenza. Jean-Francois Rossignol, Sreedhar Samudrala, Melanie Hoppers, Jason Haffizulla, Harvey Resnick, Aaron Hartman, Stefan Comhaire, Maria Carríon, Matthew Bardin. Presentation Number LB-35, Session 182a: Late Breaker Oral Abstracts - Clinical Virology and Treatment. Saturday, October 22, 2011, 6:30 PM.

About the US Clinical Trial

The clinical trial was conducted in 74 outpatient primary care centers throughout the United States during the 2010-2011 flu season. 624 patients, 12 to 65 years of age, with influenza symptoms were enrolled in the study within 48 hours of symptom onset and received treatment with 300 mg NTZ, 600 mg NTZ or placebo twice daily for 5 days. Patients who received an influenza vaccine after August 1, 2010 and patients at risk of complications of influenza based upon CDC or IDSA criteria were excluded from participation in the trial. The study was designed according to FDA Guidance and consistent with prior clinical trials of Tamiflu® and Relenza®. The primary efficacy endpoint of the study was time from first dose to alleviation of symptoms (all symptoms absent or mild and remain so for 24 hours).

Two hundred and fifty-seven (257) of the 624 patients enrolled in the study (41%) had laboratory confirmed influenza infection by RT-PCR or viral culture at baseline. Approximately half of the influenza-infected patients enrolled in the US clinical trial were infected with influenza A subtype H1N1 ("swine flu") with approximately 30% being infected with influenza B and 20% with influenza A subtype H3N2. The trial achieved its primary endpoint showing that influenza-infected patients treated with NT-300 administered 600 mg twice daily for five days experienced statistically significant reduction in time from beginning treatment to alleviation of flu symptoms compared to influenza-infected patients receiving the placebo (P=0.008). Median time to alleviation of symptoms was 95.5 hours for the 600 mg dose group compared to 109.1 hours for the 300 mg dose group and 116.7 hours for patients receiving the placebo. Time to resolution of symptoms for the low dose group were less than for the placebo, but the difference was not statistically significant (P=0.521). Patients in the 600 mg NTZ treatment group also experienced statistically significant reductions in quantitative viral shedding compared to patients receiving the placebo (P=0.0006). Adverse events were similar for the three treatment groups except for a higher rate of mild diarrhea in the 600 mg treatment group (8.1%) compared to the placebo treatment group (3.3%).

About the Phase 2 Clinical Trials

Two Phase 2 clinical trials, one in pediatric patients age 1 to 11 years, and another in adults and adolescents age 12 65 years, were conducted at a single center in Cajamarca, Peru. Patients were enrolled based upon symptoms consistent with influenza (fever, at least one respiratory symptom and one constitutional symptom) and randomly assigned to receive treatment with NTZ or placebo in double-blind fashion. Patients in the pediatric study received 100 mg NTZ (age 12 47 months), 200 mg NTZ (age 4 11 years) or placebo twice daily for five days as an oral suspension. Patients enrolled in the study of adults and adolescents received 500 mg NTZ or placebo twice daily for five days as an oral tablet. Identification of respiratory viruses at baseline was performed by ELISA. Patients were visited daily by a study nurse to monitor the health of the patients, ensure compliance with the study medication and recording of symptoms in a patient diary, and to collect tissue with nasal secretions, and patients were followed up at study day 7. The primary efficacy endpoint was time from first dose to alleviation of symptoms (all symptoms absent or mild and remained so for 24 hours).

One-hundred children, median age 3 years, were enrolled in the pediatric trial (50 per treatment group). 86 adults and adolescents were enrolled in the second trial (43 per treatment group). Respiratory viruses were detected by ELISA at baseline in only approximately 15% of the patients. In each of the two trials, treatment with NTZ was associated with a statistically significant reduction in duration of symptoms compared to the placebo. In the pediatric study, median time from first dose to alleviation of symptoms was 4 days for the NTZ treatment group compared to >7 days for the placebo treatment group (P<0.0001). In the study involving adults and adolescents, median time from first dose to alleviation of symptoms was 4 days compared to 7 days for the placebo treatment group (P=0.037). In the pediatric study, 60% of the patients in the placebo treatment group required post-study antibiotics compared to only 8% in the NTZ treatment group (P<0.0001). In the adult/adolescent study, 36% of the patients in the placebo treatment group required post-study antibiotics compared to 18% in the NTZ treatment group (P=0.13). In each study, adverse events were similar between the treatment groups.

About Influenza

Influenza is a highly contagious acute respiratory illness caused by influenza viruses including the new H1N1 influenza. Common symptoms include fever, runny nose, nasal congestion, sneezing, cough, sore throat, headache, muscle aches, sweats, chills and fatigue. Influenza illness affects all age groups and can lead to complications including sinusitis, otitis, bronchitis, pneumonia and central nervous system disease. In the United States, influenza is responsible for approximately 36,000 deaths and 216,000 hospitalizations per year.

About Romark Laboratories

Romark Laboratories, L.C. (www.romark.com) is a biopharmaceutical company committed to the discovery and development of innovative new small molecules for treating infectious diseases and cancers. The Company is developing a new class of broad-spectrum antiviral drugs called the thiazolides. Romark markets Alinia® (nitazoxanide) tablets, 500 mg and Alinia® (nitazoxanide) for Oral Suspension, 100 mg/5 mL in the United States.

SOURCE Romark Laboratories, L.C.


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