A while ago i posted on the 77% tamiflu resistance to pandemic...

A while ago i posted on the 77% tamiflu resistance to pandemic flu with new sequences in Japan - then we heard nothing more and i was wondering if it was an abberation in the way the reporting was done. Well it appears not - and this is a monumental event for BTA/GSK and LANI partners as it almost certainly signals the death nell of the competition permirivir and tamiflu. and in the biggest antiviral market in the world at that. This continued build in resistance to these two will continue and if i had the flu i would't want to be treated with them on the basis they might work - i'd want relenza, IV relenza or LANI because they do work.

This sort of news in days gone by - would have warrented a major re-rating of the stock purly on fundamentals

Fixing Tamiflu Resistance In pH1N1 In Japan
Recombinomics Commentary 20:36
March 27, 2010


NIID has released 15 NA sequences (at GISAID) and all 15 had H274Y. Five of the 15 were from 2010, which increases the number of 2010 NA sequences to seven. Six of the seven have H274Y. The frequency of H274Y in sequences released by NIID has steadily increased, but the sequence of 2010 isolates is approaching 100% (see list below).

Similar levels may be circulating elsewhere. Recent reports from the US have cited the rapid appearance of H274Y in Tamiflu treated immune-compromised patients, and the rapid detection signals transmission of a minor sub-species which is quickly detected after the start of treatment. Similar reports have been made for contacts of H1N1 who became symptomatic 5-6 days after the start of prophylactic treatment. An even shorter time frame was reported for a patient treated in Singapore, where H274Y was detected 2-3 days after the start of treatment.

The sequences from Japan are widespread geographically and fall onto many branches of a phylogenetic tree. However, there is also clustering on some branches, signaling transmission. Transmission has also been reported in Vietnam, the US, and UK, signaling transmission at multiple levels (easily detectable, as well as minor species detected after the start of treatment).

However, the high rate of H274Y in 2010 isolates may signal the emergence of new variants which have less wild type competition because of increasing immunity in the target population. In the 2007/2008 season, H274Y levels in seasonal H1N1 varied, but in 2008 in the southern hemisphere one sub-clade emerged with H274Y, and the polymorphism became fixed in the 2008/2009 season. The large number of sub-clades that are now H274Y positive raise concerns that the fixing of H274Y in seasonal H1N1 will be repeated in pandemic H1N1 in the upcoming wave.

The latest sequences from Japan suggest that the fixing may already be well on its way.

A/NIIGATA/19/2010*
A/NIIGATA/16/2010*
A/YAMAGATA/29/2010*
A/KITAKYUSYU/4/2010*
A/FUKUOKA/1/2010*
A/WAKAYAMA-C/1/2010*
A/HIROSHIMA-C/1/2010

* = H274Y