Recent events in therapeutic antibody approvals
Recombinant
therapeutic antibodies are now a major element of biopharmaceutical sales. Last
Spring a survey report by La Merie Publishing noted that antibody sales in 2014
were over $68Bn, up from $63Bn in 2013, and representing nearly half of the
$141Bn of recombinant antibody and protein sales.
The second half of 2015
saw a surge in approvals of therapeutic antibodies with 8 antibodies of various
kinds approved covering a range of applications and indications. These and
other impending approvals have been reviewed in a recent article by Jan
Reichert, (Reichert JM (2016) Antibodies to watch in 2016, mAbs, 8:2, 197-204), one
of a series produced over the last few years which concisely summarise and update
on the ever-increasing number of antibody products in market and late stage
development. The article notes a further 7 therapeutic antibodies were in
regulatory review in the US or Europe at the end of 2015 and suggests that of
53 antibodies in Phase III or II/III clinical trials, 8 of these may move to
regulatory review during 2016. Additionally 15 other products have projected
Phase III completion during 2016.
The Reichert
article notes the indications and the basis for approval of these new antibody
products and also comments on those in regulatory review and Phase III studies.
One aspect of note is the mix of technologies used to derive the products. Of
the recently approved antibodies one, Unituxin (dinutuximab, Unither), is a
chimeric antibody, the first format developed for recombinant antibodies. In
addition there were three humanised antibodies; one of these, Praxbind being a
Fab fragment. Finally four “fully human” antibodies were approved. Protrazza
(necitumumab, Eli Lilly) was generated using phage display technology whereas
the others were generated using transgenic mouse platforms: Darzalex
(daratumumab, Genmab/Janssen) from the Medarex/Bristol
Myers-Squibb transgenic
mouse technology, Repatha (evolocumab, Amgen) from Abgenix/Amgen transgenic
mice and Praluent (alirocumab, Sanofi) the first approved antibody generated
from the Regeneron transgenic mouse technology.
Of the recombinant
technologies used to generate antibodies, humanisation methods still
predominate with 24 product approvals, (not all of which are still on the
market) and many in clinical trials (from our own internal surveys well over
200 are in clinical studies), whereas the later technologies have generated 5 approved
antibodies from phage technology and 12 from the transgenic platforms. There
are additionally 5 murine and 9 chimeric antibodies still approved for
therapeutic use. We note well over 100 antibodies derived from transgenic mouse
technologies in the clinic with, as noted in the Reichert review, 12 now in regulatory
review, Phase III or Phase II/III clinical studies. Antibodies from phage
technologies are less prevalent but we still have noted over 50 in the clinic
including the 5 noted in the Reichert paper in Phase III or II/III studies.
Notwithstanding the current debate about the nomenclature for innovator
antibodies (see Jones TD et al. (2016) The INNs and outs of antibody
nonproprietary names. mAbs, 8:1, 1-9) it seems that this area will
to continue to produce a steady pipeline of products over the next few years to
add to the list of innovator therapeutic antibodies (and not counting
biosimilar products) that have been approved around the world.
In the next few
weeks we anticipate the next update of worldwide sales figures for approved antibody
products from La Merie which should further emphasise the commercial importance
of this product category.
Labels: approvals, therapeutic antibodies