IMS Company Profiles - Report Buyer

IMS COM PANY PRO FILES NOVARTIS
grade 3 and 4), nau sea (31.3% of pa tients; 1.2% with grade 3 and 4), fa tigue (26.5% of pa tients; 2.4%
with grade 3 and 4), pru ri tus (25.3% of pa tients; 3.6% with grade 3 and 4), asthenia (19.3% of pa tients;
3.6% with grade 3 and 4) and ab dom i nal pain (18.1% of pa tients; 1.2% with grade 3 and 4).
Thrombocytopenia, di ar rhea, nau sea and fa tigue were the most com mon ad verse events pos si bly re -
lated to panobinostat and thrombocytopenia was the most com mon grade 3-4 ad verse event pos si bly re -
lated to the agent. Eight pa tients had re sponse as as sessed with a com pos ite of the mod i fied
Se ver ity-Weighted As sess ment Tool (mSWAT); eight pa tients had re sponse with mSWAT plus CT scan
and 11 pa tients had re sponse with PGA (peak ground ac cel er a tion). The me dian time to response was 57
days and 21 patients experienced improvement in pruritus.
At the 20th EORTC-NCI-AACR Sym po sium on Mo lec u lar Tar gets and Can cer Ther a peu tics (Oc to ber
2008) in Geneva, Swit zer land, Novartis pre sented pre clin i cal data for panobinostat. In SCLC and NSCLC
cell lines, panobinostat in hib ited pro lif er a tion at low nanomolar con cen tra tions (IC50 5-85 nM). In SCLC
tu mor bi op sies, treat ment with panobinostat re sulted in in creased histone acetylation, p21 ex pres sion
upregulation and caspase ac ti va tion. In xenograft tu mor mod els of SCLC, panobinostat in duced sig nif i -
cant tu mor re gres sion; in NSCLC tu mor mod els it in hib ited tu mor growth. Ad di tive antitumor ef fects were
dem on strated in an H69 SCLC xenograft tu mor model when panobinostat was combined with etoposide.
Sales/An a lyst Com ment: Cowen & Co an a lysts (Au gust 2008) fore cast ini tial sales of $10 mil lion in
2010 ($80 mil lion by 2013).
SOTRASTAURIN (AEB 071) is a T-cell ac ti va tion in hib i tor that tar gets pro tein kinase C (PKC), for the
pre ven tion of trans plant re jec tion. Phase II tri als were on go ing in Eu rope in 2008. It aims to be come the
first oral treat ment that in hib its T-cell ac ti va tion since the in tro duc tion of calcineurin in hib i tors. T-cell ac ti -
va tion is an early step in au to im mune dis eases such as pso ri a sis and is also es sen tial for the re jec tion of
trans planted or gans. AEB 071 blocks a path way crit i cal to T-cell ac ti va tion and has shown prom ise in or -
gan trans plan ta tion as well as in au to im mune dis or ders. It has shown im prove ments in psoriatic skin le -
sions in an early proof-of-con cept study and has en tered started phase II trials for organ transplantation
(prevention of graft rejection).
Clin i cal Data: At the 231st Amer i can Chem i cal So ci ety na tional meet ing, in March 2006, Novartis pre -
sented data on AEB 071 for the pre ven tion of trans plant re jec tion. In pre clin i cal stud ies the agent in hib -
ited T-cell ac ti va tion but not T-cell pro lif er a tion, as well as in hi bi tion of NF-kB sig nal ing path way,
immunosuppressive ef fect and dose-de pend ent in hi bi tion of lymph node swell ing. AEB 071 was well tol -
er ated in a phase I trial in healthy volunteers in doses up to 500mg.
Sales/An a lyst Com ment: Cowen & Co an a lysts (Au gust 2008) fore cast ini tial sales of $25 mil lion in
2012 ($50 mil lion in 2013).
AEE 788, a dual in hib i tor of epi der mal growth fac tor re cep tors (EGFR) and vas cu lar en do the lial growth
fac tor re cep tors (VEGFR), was in phase I tri als in 2008 for use in a va ri ety of solid tu mors. Novartis does
not an tic i pate a fil ing for reg u la tory approval before 2011.
RAF 265 is a small-mol e cule in hib i tor of mu tant B-Raf and VEGFR kin ases in phase I tri als for mel a noma.
It has dem on strated po tent anti-tu mor ac tiv ity in pre clin i cal mod els of mu tant B-Raf. Novartis ob tained
RAF 265 via the 2005 pur chase of Chiron. In 2008, Novartis stated that it was still in phase I trials.
DOVITINIB (TKI 258) is an oral VEGFR ty ro sine kinase in hib i tor. It is in phase I tri als in var i ous can cers,
in clud ing mel a noma, and in late 2008 a phase I was be gun in met a static re nal cell car ci noma (mRCC).
De vel op ment in AML and mul ti ple myeloma was ter mi nated in 2007. Pre clin i cal stud ies showed that
dovitinib has di rect ac tiv ity against tu mor cells and against de vel op ment of tu mor vasculature. Novartis
ob tained dovitinib via the 2005 acquisition of Chiron.
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