A phase 2 clinical trial has provided further evidence of the tolerability benefits of giving bortezomib subcutaneously rather than intravenously. The evidence comes from a multiple myeloma trial that tested the proteasome inhibitor in combination with histone deacetylase inhibitor Farydak.
Novartis began a phase 3 trial of Farydak in combination with bortezomib, sold by Takeda as Velcade, in 2009 and went on to initiate another study of the cocktail the following year. However, both the clinical trials used an intravenous formulation of bortezomib. Subsequently, Takeda won approval for a subcutaneous formulation that appeared more tolerable, leading Novartis to initiate a third study in 2016.
“It was decided to explore different schedules and doses of panobinostat … but in combination with subcutaneous bortezomib, which had really become the standard of care in the utilization of bortezomib between that original randomized study and the opening of PANORAMA 3,” Andrew Spencer, a co-author on the Lancet Oncology paper about the clinical trial, told OncLive.
The latest study found the safety profile of the bortezomib-Farydak combination is better when the proteasome inhibitor is given subcutaneously rather than intravenously. Notably, the incidence of diarrhea was lower in PANORAMA 3 than in Novartis’ earlier clinical trials of the combination.
Takeda won FDA approval for Velcade for subcutaneous administration in 2012 on the strength of a pivotal trial. The study showed subcutaneous administration is as effective as intravenous delivery and is less likely to cause peripheral neuropathy. Since then, competition has intensified, but Takeda is still positioned to benefit from any increase in interest in the subcutaneous formulation.
Fresenius Kabi won FDA approval for a rival bortezomib product late in 2017. Two years later, the FDA approved another bortezomib product from Dr. Reddy’s Laboratories. Both companies won approval via the 505(b)(2) pathway, rather than the abbreviated new drug application process typically used by generics. The use of the 505(b)(2) pathway led to differences between the labels of Velcade and its two rivals, including the route of administration. The copies were approved for use intravenously.
Novartis sold the global rights to Farydak to Secura Bio in 2019.