Amgen 2009 Annual Report Download - page 49

and intermediate risk MDS currently receiving either decitabine or lenalidomide showed reduced incidence of
clinically significant thrombocytopenic events and platelet transfusions with the addition of Nplate®treatment.
We are also evaluating Nplate®in chemotherapy-induced thrombocytopenia.
Omecamtiv mecarbil (AMG 423)
Omecamtiv mecarbil is a small molecule activator of cardiac myosin. Omecamtiv mecarbil is being inves-
tigated to improve cardiac contractility in subjects with heart failure. We are developing this product in
collaboration with Cytokinetics, Inc. (“Cytokinetics”).
In May 2009, Cytokinetics and Amgen Inc. announced that Amgen had exercised its option to obtain an ex-
clusive license, worldwide (excluding Japan), to Cytokinetics’ cardiac contractility program, which includes
omecamtiv mecarbil.
Sensipar®(cinacalcet)
Sensipar®/Mimpara®is an orally-administered small molecule that lowers PTH levels in blood by signaling
through the calcium-sensing receptor in parathyroid tissue to inhibit PTH secretion. It also lowers blood calcium
and phosphorous levels.
The phase 3 EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (“E.V.O.L.V.E.™”) tri-
al, initiated in 2006, is a large (3,800 patient), multi-center, international, randomized, double-blind study to
assess the effects of Sensipar®on mortality and cardiovascular morbidity in patients with CKD undergoing main-
tenance dialysis. The E.V.O.L.V.E.™study completed enrollment in January 2008. Based on current event rates,
we anticipate completion of the study in dialysis patients in 2011.
Vectibix®(panitumumab)
Vectibix®is a fully human monoclonal antibody antagonist of the EGFr pathway. It is being investigated as
a cancer treatment.
In September 2009, we announced detailed results from the phase 3 ‘181 trial evaluating Vectibix®in
combination with FOLFIRI (an irinotecan-based chemotherapy), as a second-line treatment for mCRC. The ‘181
trial is a global, multicenter, randomized phase 3 study. Patients enrolled in the study were randomized to receive
either 6.0 milligram/kilogram of Vectibix®and FOLFIRI once every two weeks or FOLFIRI alone once every
two weeks. The independently tested co-primary endpoints were PFS and OS. Secondary endpoints included ob-
jective response rate, time to progression, duration of response and safety by KRAS status. Originally designed to
compare the treatment effect in the overall population, the study was amended to analyze outcomes with respect
to the presence or absence of activating mutations in KRAS. Tumor KRAS status was ascertained in 91% of the
1,186 patients enrolled in this trial, the highest number ever reported for a second-line trial. In this trial, Vecti-
bix®significantly improved PFS in patients with KRAS wild-type mCRC. The addition of Vectibix®to FOLFIRI
significantly improved median PFS (co-primary endpoint) by two months (5.9 months versus 3.9 months for pa-
tients treated with FOLFIRI alone, HR: 0.73, p=0.004) in patients with KRAS wild-type mCRC. Although
numerically greater (14.5 months versus 12.5 months, HR: 0.85), the improvement in median OS (co-primary
endpoint) in the Vectibix®arm did not achieve statistical significance (p=0.115) in the same patient population.
Further, the addition of Vectibix®to FOLFIRI resulted in greater than a three-fold improvement (35% versus
10%) in response rate in the KRAS wild-type patient population as measured by a blinded central review. In gen-
eral, adverse events rates were comparable across arms with the exception of known toxicities associated with
anti-EGFr therapy such as rash, diarrhea and hypomagnesemia. Vectibix®-related grade 3/4 infusion reactions
were reported in less than 1% of patients. There were no differences in PFS, OS and response rates among pa-
tients with mutated KRAS who received Vectibix®. Tumor KRAS tests were finalized after the completion of
enrollment and prior to the primary analysis.
Also in September 2009, we announced detailed results from the phase 3 ‘203 trial evaluating Vectibix®
administered in combination with FOLFOX (an oxaliplatin-based chemotherapy) as the first-line treatment of
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