IMS Company Profiles - Report Buyer

IMS COM PANY PRO FILES TAKEDA
Phase III data pre sented at the Amer i can Col lege of Rheumatology in Texas in Oc to ber 2004 in cluded a
TAP-spon sored study, which was de tailed in a late-break ing ab stract ses sion, and two Teijin-spon sored
stud ies con ducted in Ja pan, named FAL CON and FLIGHT. TAP’s head-to-head com par i son of febuxostat
(80 or 120 mg/day) with allopurinol (300 mg once daily) found in fa vor of febuxostat. IN the 760-pa tient,
one-year study, more pa tients on the TAP/Teijin com pound met the pri mary end point (UA lev els of less
than 6.0 mg/dl at each of their last three monthly mea sure ments) than those on allopurinol. All pa tients
en rolled had gout and lev els of sUA greater than 8.0 mg/dl at the start of the trial. Febuxostat did not sig -
nif i cantly re duce tophus area (ag gre gates of urate crys tals) at 52 weeks, but the higher dose showed sig -
nif i cance on this end point at an ear lier time point in the trial. How ever, pa tients who did reach the goal of
sUA of less than 6 mg/dl in all treat ment groups had fewer gout at tacks and a greater median reduction in
tophus area.
The FAL CON study also found a fa vor able com par i son on febuxostat with allopurinol. It used a lower dose
of both drugs than the TAP study (40 mg af ter an in tro duc tory 12 days at 10 mg and allopurinol at 100 mg
bid). The pa tients tak ing febuxostat has a 40.5% de crease over base line lev els of sUA at the end of the
44-day trial, com pared with a 33.9% re duc tion in the allopurinol group. Febuxostat seemed to work just
as well in pa tients who were un der-excretors of uric acid as in those who has hyperuricemia. The phase
III trial had a sim i lar safety pro file of the TAP trial.
The six-week FIGHT trial dem on strated that sig nif i cantly more pa tients on febuxostat (20 or 40 mg) had
less than 6mg/dl de creases in sUA com pared with pla cebo. At least one ad verse event was seen in 71.0%
of febuxostat-treated pa tients, com pared with 79.4% of pa tients on pla cebo. Those as so ci ated with
febuxostat in cluded gout flare, in creases in C-re ac tive pro tein and creatinine phosphokinase, and the
common cold.
Com pe ti tion: An es ti mated 5.1 mil lion peo ple suf fer from Gout in the USA. Cur rent first line (gold stan -
dard) ther apy for gout is the ge neric XAO allopurinol (Zyloric), first ap proved in 1966, but about 2% of
pa tients are al ler gic to this drug and fewer than half of pa tients achieve tar get se rum uric acid (sUA) lev -
els of less than 6mg/dl. There is a need for new gout ther a pies and if ap proved, Uloric will be the first new
oral drug ap proved in the US for gout in the last 40 years. A num ber of re cent drugs have been de nied ap -
proval. For ex am ple, an other XAO oxypurinol (allopurinol’s ac tive me tab o lite) Oxyprim was be ing de vel -
oped by Cardiome (Can ada) for use in gout and con ges tive heart fail ure but this was as so ci ated with a
num ber of deaths and did n’t get past the ar thri tis ad vi sory com mit tee in 2004. Merck & Co had hoped to
gain an in di ca tion in gout for its COX-2 in hib i tor Arcoxia (etoricoxib) but the NDA was re jected by the
FDA in 2007 due to associated cardiovascular risk.
An a lyst at Mor gan Stan ley con sider that febuxostat of fers a mean ing ful al ter na tive for gout treat ment to
the cur rent stan dard. It could ben e fit re nal pa tients due to be ing ex creted pre dom i nantly via the liver
(ver sus re nal ex cre tion for allopurinol). Febuxostat (80mg) has also shown good ef fi cacy with 25-38%
more pa tients reach ing less than 6mg/dl sUA than allopurinol with the 40mg dose show ing 20-22%
higher pa tients achiev ing these lev els; both doses showed en hanced ef fi cacy in pa tients with
mild-to-mod er ate re nal im pair ment. Fur ther more, the CON FIRMS study did not show any in creased car -
dio vas cu lar events were than with allopurinol.
The de ci sion on febuxostat could af fect other gout ther a pies in de vel op ment. The next clos est to mar ket
is Savient’s pegloticase, a pegylated mam ma lian urate oxidase un der de vel op ment for the treat ment of
hyperuricemia in pa tients who have failed to nor mal ize se rum uric acid lev els with con ven tional ther apy
or for whom con ven tional ther apy is con tra in di cated; the com pany hopes to file dur ing 2009 but it has
shown some car dio vas cu lar ad verse events and in fu sion re ac tions. Pfizer has also an nounced plans to
sub mit its COX-2 inhibitor Celebrex for gouty arthritis.
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