dm+d

Unassigned

New Medicines

Aplivab (EU), Rapivab (US) Influenza

Information

Aplivab (EU), Rapivab (US)
New molecular entity
BioCryst Pharmaceuticals
Seqirus

Development and Regulatory status

Licensed but not launched
Launched
Launched
Apr 22Biocryst have no plans to launch in UK. [30]
Jun 21Launched for influenza virus infections in Netherlands, Poland, Portugal (IV). [29]
Mar 20Agreement between Seqirus UK and Biocryst Pharmaceuticals relating to the commercialisation of peramivir worldwide terminated. Plans for launch are therefore uncertain. [28]
May 18BioCryst has a license agreement with Seqirus regarding peramivir. BioCryst and Seqirus are engaged in a formal dispute resolution process. The dispute involves many items under the contract including, but not limited to, the EMA approval milestone of $5 million dollars, which BioCryst maintains is now due under the agreement [27].
Apr 18Alpivab received a marekting authorisation valid throughout the EU [26].
Feb 18Positive opinion from CHMP "for the treatment of uncomplicated influenza in adults and children from the age of 2 years"; EU brand name will be Aplivab [22].
Jan 17MAA submitted to the EMA for intravenous peramivir for treatment of influenza in adults aged over 18 years who have been symptomatic for no more than two days [20].
Oct 16Marketed USA (also Japan, South Korea, Taiwan) [19].
Jan 16There appears to be no development in the EU [16].
Jun 15Worldwide commercialisation rights except Japan, Korea, Taiwan & Israel licensed to Sequirus UK, except for US government stockpile procurement [18].
Mar 15PIII in EU (including UK) for hospitalised patients with influenza A & B [15].
Dec 14FDA has approved peramivir (Rapivab®), a neuraminidase inhibitor given as a single dose (IV infusion) for the treatment of acute uncomplicated influenza.
Dec 13Filed in the US for the treatment of acute uncomplicated influenza in adults [12].
Jul 13BioCryst is planning to file in the US by the end of 2013 for the treatment of acute uncomplicated influenza based on PII trials [11].
Apr 13A preliminary comment letter from the FDA outlines a pathway by which BioCryst could file a New Drug Application (NDA). The FDA suggested the Company request a pre-NDA meeting to reach agreement on a complete NDA submission and to address review issues identified in its preliminary comment letter [10].
Nov 12After an interim analysis, the independent data monitoring committee for the PIII 301 study recommended that the study be terminated. it is unlikely that peramivir development for US registration will continue [9].
Oct 10Slow enrolment in PIII study may delay launch to 2013 [8].
Sep 09PIII studies to start Sep 09 [6].
Jan 08PIII trials expected to begin in 2008 [2].
Jan 06Fast tracked in US for influenza [1].

Category

Neuraminidase inhibitor
2 January 2016Up to 15% of the population can develop influenza in any year. There is a 10-20% seroconversion rate with or without symptoms. In an average year, there are 50-200 GP consultations for influenza or flu-like illnesses per 100,000 population per week (patient .co.uk)
Influenza
Intravenous

Further information

Yes

Trial or other data

Feb 18No further development reported [23-25].
Nov 12Results of the planned interim analysis of the peramivir PIII ‘301’ trial in patients admitted to the hospital with serious influenza reported the difference between peramivir and control groups for the primary endpoint was small and the recalculated sample size was greater than the predefined futility boundary of 320 subjects [9].
Jan 11The ‘301’ ongoing PIII study is evaluating the efficacy and safety of 600mg peramivir once-daily for 5 days in addition to standard of care (SOC), vs SOC alone, in adults and adolescents hospitalized due to serious flu. BioCryst has requested US regulatory approval for modifications in the conduct of the study including: revision of the primary efficacy analysis, to focus on patients not treated with neuraminidase inhibitors as SOC; increasing the sample size and including more sites; adding geographical regions and extending the timeline to complete enrollment beyond the end of 2011 [8].
Jan 11Top-line results from the ‘303’ PIII open-label, randomized trial of IV peramivir 600mg once-daily or 300mg twice-daily reported. The study enrolled 230 subjects (aged 14-92) hospitalized with confirmed or suspected flu during the 2009-2010 H1N1 pandemic; 200 patients (85%) had symptoms for more than 48 hours. Treatment was planned for 5 days with an optional extension to 10 days. 170 patients (74%) had received prior oseltamivir. The intent to treat infected (ITTI) population consisted of 127 patients with confirmed flu. The primary endpoint was change in influenza virus titer in nasopharyngeal samples, measured by log10 tissue culture infective dose50 (TCID50). 44 patients had a positive baseline culture, 20 in the 300mg group and 24 in the 600mg group. Reductions in log10 TCID50 titre were -1.66 and -1.47, respectively, in the two groups over the first 48 hours. Overall 28 day mortality was 8.7%. In the combined ITTI population median time to resolution of fever was 25 hours; time to clinical resolution, 92 hours; time to alleviation of symptoms, 145 hours; and time to resumption of usual activities, 26.8 days [8].
Oct 09The FDA has issued an emergency use authorization (EUA) for peramivir in hospitalised adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza infection for whom therapy with an IV drug is clinically appropriate, based on one or more of the following: 1] the patient is not responding to either oral or inhaled antiviral therapy, 2] when drug delivery by a route other than an intravenous route is not expected to be dependable or feasible, or 3] for adults only, when the clinician judges IV therapy is appropriate due to other circumstances [7].
Sep 09BioCryst has been awarded a $77.2 million contract modification by the US Department of Health & Human Services to complete PIII development of peramivir for the treatment of complicated influenza. Two PIII studies are planned. NCT00957996 is an open-label, randomised study in 300 adult and adolescent hospitalised subjects with confirmed or suspected influenza infection; they will receive peramivir 300mg twice daily or 600mg daily. The study will start Sep 09 and complete in Jun 2011. The primary outcome is reduction in influenza virus titre measured by log10 tissue culture infective dose50. NCT00958776 is a multicenter, randomised, double-blind, placebo controlled study of peramivir in addition to standard of care compared to standard of care alone in 400 adults (600mg daily) and adolescents (10mg/kg daily) hospitalised due to serious influenza. Study start is Nov 09 and completion May 2011. The primary outcome is time to clinical resolution [6].
Jul 09BioCryst is supporting the pre-emergency use authorisation review of peramivir by the FDA. In May, BioCryst said that government agencies were considering the future option of providing IV peramivir through an emergency use authorisation in the event of a severe influenza outbreak with significant hospitalisations [5].
Jul 09Results reported from 2 Japanese/Korean PIII studies in patients with seasonal flu during the 2008-2009 season. In one study, 1,099 patients with uncomplicated flu were randomized a single dose of IV peramivir (300 mg or 600 mg) or oseltamivir 75 mg twice a day for 5 days. Non-inferiority was demonstrated in the peramivir groups for the primary endpoint, time to alleviation of symptoms (TTAS). The medians for TTAS were 78.0 hours, 81.0 hours and 81.8 hours, respectively. In the second study in 42 patients at high-risk of serious complications because of co-morbidity, 300 or 600mg IV permavir/day was given for up to 5 days. The median TTAS in 37 evaluable patients was 68.6 hours. BioCryst is finalising plans for PIII studies to support FDA approval [4].
Jul 08PII trial results - 300 pts randomised to either placebo or one of two doses of peramavir (300mg or 600mg) within 48 hrs of onset of symptoms. Primary outcome of improvement in the median time to alleviation of symptoms in pts with confirmed, acute, uncomplicated influenza infection, vs. placebo alone. Peramavir was generally well tolerated [3].
Jun 02C3 trials begun in Feb00. Developmental delays reported Nov 00, as two C3 trials in the elderly are not going ahead for logistical reasons. BioCryst continuing develop and are seeking a partner for final development and marketing. Development stopped after a phase 3 trial failed to show any significant benefit

Evidence based evaluations