Biota Pharmaceuticals, a biopharmaceutical company focused on the discovery and development of products to prevent and treat serious and potentially life-threatening viral respiratory infectious diseases, announced top-line data from a randomised, double-blind, placebo-controlled, parallel-arm phase 2 clinical trial comparing the safety and efficacy of a 40 mg and 80 mg dose of laninamivir octanoate (LANI) to placebo.
The trial, referred to as IGLOO, enrolled 639 patients across 12 countries in the Northern and Southern Hemisphere from June 2013 to April 2014. Of the 639 patients enrolled, 248, or 39 per cent, had PCR confirmed influenza A or B virus and were included in the intent-to-treat efficacy analyses. Approximately 75 per cent and 19 per cent of the influenza-confirmed patients were infected with influenza A H1N1 2009 and H3N2, respectively, with 6 per cent being infected with influenza B.
As compared to placebo, neither the 40 mg or 80 mg cohort achieved a statistically significant reduction in the median time to alleviation of influenza symptoms as measured by the Flu-iiQ patient-recorded outcome questionnaire (p=0.248 and p=0.776, respectively), which was the primary endpoint of the study. The median time to alleviation of influenza symptoms was 102.3 hours for the 40 mg cohort and 103.2 hours for the 80 mg cohort, as compared to 104.1 hours for the placebo cohort.
Patients in both the 40 mg (p < 0.001) and 80 mg (p=0.070) cohorts demonstrated a statistically significant reduction in viral shedding on Day 3 of the study compared to placebo as quantified by qRT-PCR. In addition, a statistically significant proportion of patients in both the 40 mg (p=0.002) and 80 mg (p=0.020) cohorts were culture negative on Day 3 of the study as compared to placebo. Influenza-infected patients in the 40 mg cohort also demonstrated a statistically significant reduction in the incidence of secondary bacterial infections as compared to placebo (p=0.013). The nature and extent of adverse events were similar in the three cohorts, with diarrhoea (3.1 per cent vs. 0.9 per cent), headache (1.4 per cent vs. 0.5 per cent), gastritis (1.4per cent vs. 0 per cent), urinary tract infection (1.4 per cent vs. 0 per cent), and sinusitis (1.2 per cent vs. 0.9 per cent) being the most common adverse events that occurred more frequently in the treatment cohorts as compared to placebo. The incidence of serious adverse events was low and balanced across the three cohorts.
"It is disappointing that the rapid and significant onset of antiviral activity against the influenza virus that the two treatment arms demonstrated with LANI did not translate into a meaningful reduction in the time to alleviate patient-reported influenza symptoms," stated Russell H. Plumb, the company's president and chief executive officer, "We expect to complete a full analysis of additional clinical, safety, and pharmacokinetic data forthcoming from this trial over the next several months; however, at this time we do not have any plans to independently advance the development of LANI for the treatment of influenza and intend to evaluate next steps for the LANI programme outside of Japan with our partner, Daiichi Sankyo."
The company plans to provide a detailed update on the full efficacy and safety results of the Phase 2 IGLOO trial, the status of the LANI programme and its corporate strategy during its fourth quarter and fiscal year-end earnings call in early September.
Laninamivir octanoate is a second-generation octanoyl ester prodrug of laninamivir that has demonstrated in vitro neuraminidase-inhibitory activity against influenza A and B viruses, including subtypes N1 to N9, swine origin H1N1 strains and oseltamivir-resistant viruses. Laninamivir octanoate has long-lasting antiviral activity and exhibits a calculated half-life of approximately 58 hours in the respiratory tract. In a previous Phase 3 clinical trial, a single 40 mg inhaled dose of laninamivir octanoate exhibited efficacy similar to that of daily repeated doses of oseltamivir phosphate.
In 2003, the company and Daiichi Sankyo cross-licenced intellectual property related to long-acting neuraminidase inhibitors, of which the lead product, laninamivir octanoate, has been successfully developed and subsequently marketed in Japan by Daiichi Sankyo as Inavir for the treatment and prevention of influenza A and B infections. The Company has been developing laninamivir octanoate outside of Japan for the treatment of influenza A and B infections.