Novartis and Secukinumab (AIN457)
Novartis has announced results from the head-to-head Phase III
psoriasis study which showed the superiority of secukinumab
(AIN457) in clearing skin to Enbrel®* (etanercept), an anti-tumor
necrosis factor (anti-TNF) therapy. In addition, secukinumab
(AIN457) met all primary and secondary endpoints.
The FIXTURE trial (the Full year Investigative eXamination of
secukinumab vs. eTanercept Using 2 dosing Regimens to determine
Efficacy in psoriasis) was a randomized, double-blind,
double-dummy, placebo-controlled, multicenter global study
of subcutaneous secukinumab (AIN457) in moderate-to-severe
plaque psoriasis involving 1,307 patients. It was designed to
demonstrate efficacy after 12 weeks of treatment, compared to
placebo and etanercept, and to assess the safety, tolerability
and long-term efficacy up to 52 weeks. Established treatment
measures were used to assess the efficacy of secukinumab
(AIN457) including PASI 75 (Psoriasis Area and Severity Index
75) and the Investigator’s Global Assessment (IGA mod 2011).
The secukinumab (AIN457) Phase III clinical trial program involved
more than 3,300 patients in over 35 countries on five
continents. Primary endpoints for four studies related to PASI
75 and IGA (IGA mod 2011) and the fifth study evaluated the
proportion of patients who maintained PASI 75 after having
achieved PASI 75 after 12 weeks of active treatment. The studies
evaluated 150 mg and 300 mg doses of secukinumab (AIN457).
Promius Pharma LLC, has announced the introduction of ZenataneTM (Isotretinoin) Capsules, a newly approved isotretinoin
option for patients with severe, recalcitrant, nodular acne.
Zenatane, an AB rated equivalent to Accutane®, will be supported
by The Promius Promise, a pharmacy service designed
specifically to support Zenatane prescribers and patients. The
program may help improve patient and physician experiences
by increasing educational support and reducing patient out of
pocket expenses. Promius Pharma has partnered with an accredited,
iPLEDGE™-certified, US-based pharmacy to power
The Promius Promise. The program is designed to assist with
patient education about treatment requirements and deliver
Zenatane within 24 hours to US locations, at a reduced, if not
zero, out of pocket expense, for eligible patients.
GSK and Dabrafenib/Trametinib Combination in
GlaxoSmithKline (GSK) has announced submission of supplemental
New Drug Applications (NDAs) to the FDA for use of
dabrafenib, a BRAF inhibitor, in combination with trametinib,
a MEK inhibitor. Supplemental applications were submitted to
each of the currently approved NDAs for the use of each drug in
combination with the other, for the treatment of adult patients
with unresectable or metastatic melanoma with a BRAF V600 E
or K mutation.
The applications are based on data from a randomized Phase
I/II study comparing dabrafenib monotherapy to combination
therapy with dabrafenib and trametinib in patients with BRAF
V600E and V600K mutation positive metastatic melanoma.
Use of dabrafenib and trametinib in combination is investigational
and not approved anywhere in the world. European
review of the submission for trametinib, both as monotherapy
and in combination with dabrafenib, is ongoing.
Ipilimumab and Advanced Melanoma
Clinical Cancer Research has published a study report authored
by Jeffrey S. Weber, Moffitt Cancer Center, et al. of a
retrospective analysis conducted to characterize ipilimumab
exposure–response relationships for measures of efficacy and
safety in patients with advanced melanoma.
Data were pooled from 498 patients who received ipilimumab
monotherapy at 0.3, 3, or 10 mg/kg in 1 of 4 completed phase
II clinical trials. The relationships between steady–state ipilimumab
trough concentration (Cminss), complete or partial tumor
response (CR or PR), and safety [immune-related adverse
events (irAEs)] were described by logistic regression models.
The relationship between exposure and overall survival was
characterized using a Cox proportional–hazards model.
The steady-state trough concentration of ipilimumab was found
to be a significant predictor of a CR or PR (P < 0.001). Modelbased
estimates indicate that the probabilities of a CR or PR at
median Cminss for the 0.3, 3, and 10 mg/kg groups were 0.6%,
4.9%, and 11.6%, respectively. Overall survival at the median
Cminss for ipilimumab at 0.3 mg/kg was estimated to be 0.85-