Today at BIO
CEO 2014, Tekmira presented tantalizing preclinical data (slide 11) showing more than 95% reductions in serum triglycerides,
the lipids that clog up your arteries (think heart disease and stroke) and in
extremely high cases cause severe bouts of pancreatitis. Such
reductions in triglycerides are unprecedented as fiddling around with fish
oils, fibrates, and niacins has become a worn, unsatisfactory edge in managing
this important lipid.
Enter RNA(i)
Therapeutics. By taking full advantage
of the technology in being able to target any gene in the pathways
leading up to triglyceride production and accumulation, we are not far away from
achieving much more pronounced lowerings than the current standard of medical care. This was impressively illustrated by
the 70-80% lowerings of serum triglyceride in the phase II studies with
ISIS-ApoCIIIRx, an RNaseH antisense compound by ISIS Pharmaceuticals.
If you have
been following my blog, however, I believe that despite the ISIS head-start, this
lunch will eventually be eaten by RNAi Therapeutics. In addition to their superior ability to effect gene
knockdown in the liver, the Tekmira data went one step
further to fully take advantage of the mechanistic opportunities offered by
RNAi Therapeutics, in particular those delivered by technologies such as SNALP
LNPs: multi-targeting.
As pioneered
by SNALP-enabled TKM-EBOLA and ALN-VSP02 (for liver cancer), SNALP LNPs lend
themselves to targeting multiple genes in a single drug. As a consequence, it should be relatively
easy to come up with a target combination that can not only lower serum
triglycerides more potently than could be achieved by targeting a single gene such as ApoCIIIRx, but also lower liver triglycerides (à fatty liver, fibrosis), improve
insulin sensitivity and the lipid profile on other fronts such as
LDL-cholesterol. Such a profile would be
highly attractive since a given patient often will suffer from a number of
these conditions (metabolic syndrome).
For Tekmira,
as for ISIS Pharmaceuticals, the first markets, however, will be the severe orphan diseases related to triglycerides such as those involving severely
elevated levels of serum triglycerides (>500) leading to pancreatitis. Depending on the safety and tolerability
profile, the market potential beyond these indications could be considerable
and possibly limited by the inconvenience
of having to go for monthly infusions.
But
seriously, if you are going to take a medicine that costs on the order of $100k
a year, you better take what is medically best for you and it would most likely
still be a pharmacoeconomic steal if you charged the system for taking a stretch limousine to the infusion center to take care of the inconvenience (I'm particularly keeping an eye here on how the MS market evolves). At least this primacy of efficacy is where I
am hoping the healthcare cost discussion will steer the market in the future. As such, Tekmira should not by shy in focusing
on its competitive strength of achieving maximal target knockdowns.
