13 November, 1998: Zanamivir (Relenza) has been shown to cut the time to recover from influenza by up to one-third in otherwise healthy patients, and reduce complications from influenza by 71 per cent in high risk patients. These were the results of two Phase III clinical trials of zanamivir reported today at the 36th meeting of the Infectious Diseases Society of America (IDSA) in Denver, Colorado, USA (November 12-15, 1998).
The first study, conducted in Europe in the winter of 1997/8, recruited 356 patients, of whom 78 per cent (277) were confirmed to have influenza infection, and 32 (9 per cent) were classified as 'high risk'. Patients were given either placebo or orally inhaled zanamivir at 10 mg twice-daily (bd) for five days, in the double-blind, randomised trial. The primary endpoint of the trial was median time to alleviation of clinically significant symptoms of influenza, measured by the patient's own assessment as an absence of fever and a score of 'none' or 'mild' for headache, cough, sore throat and myalgia. Zanamivir reduced the severity of all these symptoms and loss of appetite as confirmed by the investigator's assessment. High risk and otherwise healthy zanamivir-treated patients experienced relief from symptoms two and a half days sooner than placebo treated patients, a highly significant difference in the otherwise healthy group (p<0.001).1
Dr. Douglas Fleming, Birmingham Research Unit, Royal College of General Practitioners, UK, and principal investigator of the study said: "The trial confirmed that zanamivir provided significant treatment benefits. We observed a significant reduction in the severity of symptoms reported by all patients, so zanamivir not only reduced the duration of illness, but also made it less debilitating. These results convincingly demonstrate the efficacy of zanamivir."
Compared with those receiving placebo, patients taking zanamivir experienced fewer complications (9 per cent less, p=0.037) and returned to their normal activities faster (1.75 days faster, p=0.023).
These findings were strongly reflected in the second trial of zanamivir2 reported at the IDSA meeting by Adrian Griffin on behalf of MIST (Management of Influenza in the Southern hemisphere Trialists). This randomised, double-blind study involved 455 patients who were treated with zanamivir 10 mg bd or placebo for five days, and followed up for 28 days. A substantially high proportion of patients (76, 16.7 per cent) were classified as high risk in this study, which revealed a 71 per cent reduction in complications (p=0.004)3 and a 65 per cent reduction in associated antibiotic usage (p=0.025) in these patients.
Patients were asked to report similar parameters to those in the European trial, including health status, days incapacitated, and time taken to return to normal activities. In patients with confirmed influenza infection, a two-day reduction was observed in time taken to return to normal activities (p<0.001) with zanamivir treatment. Compared with the placebo group, patients treated with zanamivir reported less interference with work and recreational and leisure activities. They also reported significantly better health status scores and greater satisfaction with medication compared with the placebo group. All these differences were shown to be statistically significant.
When treating influenza with the currently available antiviral agents, such as amantadine and rimantadine, resistant virus emerges readily; however, resistance has not been detected in the treatment studies with zanamivir. Zanamivir is the first orally inhaled drug in a new generation of specific treatments against the influenza virus known as neuraminidase inhibitors, which work by interfering with the life cycle of the influenza virus. It blocks the neuraminidase enzyme on the surface of the virus, thus preventing its release from the cell, and inhibiting it from spreading to neighbouring cells within the respiratory tract. Administering zanamivir via an inhaler ensures that the drug is delivered directly to the surface of the respiratory tract - the only site of influenza virus infection in humans. It also means that high levels of the drug reach the site of virus replication.
Zanamivir has been developed by Glaxo Wellcome under licence from an Australian company, Biota Holdings. This licence gives Glaxo Wellcome the right to develop and market zanamivir worldwide.
The first application to market the product was made in Australia at the end of March 1998. Regulatory submissions for zanamivir, to be marketed under the tradename Relenza have recently been made in the US, Canada and Europe.
Glaxo Wellcome is a research-based pharmaceutical company whose people are committed to fighting disease by bringing innovative medicines and services to patients throughout the world and the healthcare providers who serve them.
Relenza is a trademark of the Glaxo Wellcome group of companies.
References
1. Fleming D et al. 'High risk' and otherwise healthy patients demonstrate
alleviation of influenza symptoms 2.5 days earlier following inhaled zanamivir
treatment; European Study, Winter 1997/8. 36th Meeting of the IDSA, Denver,
Colorado, USA, November 12-15, 1998; Abstract No: 789
2. Silagy CA et al. Impact of zanamivir on health status, productivity and
health care resource use in patients with influenza. . 36th Meeting of the
IDSA, Denver, Colorado, USA, November 12-15, 1998; Abstract No 36
3. Silagy CA et al. On behalf of MIST (Management of Influenza in the Southern
Hemisphere Trialists). The efficacy and safety of zanamivir in the treatment of
influenza in otherwise healthy and high risk adults. 38th Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Diego,
California, USA, September 24-27, 1998. Abstract H56
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