IMS Company Profiles - Report Buyer

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Orig i na tor Teijin (Ja pan) is con duct ing phase III tri als in Ja pan. In May 2005, Teijin an nounced that the
Jap a nese reg u la tory au thor i ties would re quire ad di tional clin i cal tri als to be con ducted for the drug, which
had been sub mit ted for ap proval in Ja pan in April 2004 for the treat ment of gout and hyperuricemia.
Li cens ing: Febuxostat was li censed to TAP, the jv be tween Abbott and Takeda, in 1999 by orig i na tor
Teijin. Un der the terms of the deal, TAP will de velop the drug in the USA, and has been granted mar ket ing
rights in Can ada and the USA. Teijin has also li censed rights to Ipsen in Eu rope, where febuxostat was ap -
proved in May 2008 and SK Chem i cal in South Ko rea. Takeda re ceived North Amer i can rights to
febuxostat in May 2008 fol low ing the con clu sion of a joint ven ture be tween Abbott and Takeda (TAP).
Clin i cal Data: The Third trial, CON FIRMS, was con ducted in 2,269 sub jects in which Takeda eval u ated
the ef fi cacy and safety of 40mg and 80mg doses of febuxostat com pared with stan dard treat ment
allopurinol for six months. Re sults showed non in fe ri or ity to allopurinol at the lower dose and sta tis ti cally
sig nif i cant su pe ri or ity in the higher dose where 67% of pa tients tak ing 80mg dose and 45% in the 40mg
dose and 42% tak ing allopurinol reached the pri mary end point of se rum uric acid (sUA) lev els be low
6mg/dl. Fur ther more, both doses were su pe rior to allopurinol in pa tients with mild-to-mod er ate re nal im -
pair ment. Few car dio vas cu lar events were re ported and these were even be tween the groups febuxostat
(16) and allopurinol (17) al though the FDA ad vi sory group could not ex clude the pos si bil ity which is ex ac -
er bated by the in creased car dio vas cu lar risk in this pa tient pop u la tion (1.5 times greater than the gen eral
pop u la tion). The ad vi sory group has ques tioned the popultation of pa tients which did not in clude el derly
in di vid u als that would man i fest a truer pic ture of pos si ble car dio vas cu lar mor bid i ties as well as the
six-month time frame which would be too short to un cover car dio vas cu lar risks in a drug that will be
taken for life. It was counterargued that the un met med i cal need superceded the po ten tial car dio vas cu lar
risk. The com mit tee rec om mended that any re main ing ques tions con cern ing car dio vas cu lar safety be
ad dressed by a ran dom ized clin i cal trial and an ob ser va tional study that would fol low pa tients for car dio -
vas cu lar events. Takeda has al ready pro posed a phase IV clin i cal out comes study focusing on prevention
of gout flares and all aspects of safety, the design of which it says is fluid and yet to be discussed with the
FDA.
Re sults pre sented at the Amer i can Col lege of Rheumatology meet ing in 2002 sug gested that the drug is
safe and ef fec tive in the treat ment of hyperuricemia and gout. In a phase II trial in volv ing 145 pa tients,
febuxostat sig nif i cantly re duced se rum urate lev els at all doses tested (40-80 mg once daily) and was well
tol er ated for up to four weeks. The only se ri ous ad verse ef fects thought to be pos si bly re lated to
febuxostat was one case of Guillain-Barre syndrome.
In Oc to ber 2004, TAP an nounced re sults from its phase I and II clin i cal tri als of febuxostat for gout at the
68th An nual Sci en tific Meet ing of the Amer i can Col lege of Rheumatology. Study find ings showed that
treat ment with the novel com pound low ered uric acid lev els. More over, in the ma jor ity of these pa tients,
long-term treat ment with febuxostat (up to two years) re sulted in sig nif i cant re duc tion and main te nance
of se rum urate (sUA) lev els be low 6.0mg/dl. Study par tic i pants were ini tially given 80 mg/day of the
com pound and the dose was then ad justed as nec es sary to ei ther 40 mg/day or 120 mg/day and were to
achieve a sta ble dose by study week 28 based on sUA lev els. A to tal of 116 pa tients be gan the open-la bel
study for at least two years. Pa tients ex hib ited rapid re duc tion in sUA lev els and most (74-81%) pa tients
main tained sUA levels of less than 6.0 mg/dl throughout the study.
In De cem ber 2004, TAP Phar ma ceu ti cal Prod ucts an nounced that it had sub mit ted an NDA with the FDA
for 80 and 120 mg febuxostat for the man age ment of hyperuricemia in pa tients with chronic gout. The
NDA sub mis sion in cludes one of the larg est phase III stud ies of chronic gout pa tients in the United States
to date. Ex perts rec og nize that the stan dard goal in the treat ment of chronic gout is the re duc tion and
main te nance of sUA lev els of less than 6 mg/dL. The over all in ci dence of ad verse re ac tions in clin i cal stud -
ies was sim i lar among treat ment groups. The most com monly re ported ad verse re ac tions were: liver
func tion test ab nor mal i ties, di ar rhea, head ache and nau sea. Ad verse events among trial par tic i pants
were generally self-limiting and mild-to-moderate in severity.
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