Last year, as I was researching the hereditary angioedema (HAE) therapeutics
landscape, I came across data in the C1 inhibitor gene regulation literature
that gave me a proverbial heureka moment: if I could do ‘X’, then I would have a
cure for HAE. Dazed by the excitement of being in possession of such an idea, I
verified that the enabling technologies (genome editing and LNP delivery) were
fit for purpose.
It basically seemed that all I had to do was to verify my
approach in tissue culture and the rest would be ‘simple’ business development.
In the vast majority of cases, HAE is caused by mutations in the C1 Inhibitor
gene. It is a rare disease affecting close to 10000 patients in the US and EU.
Nevertheless, it is a lucrative, currently ~5B market with therapeutics mostly
replacing missing C1 inhibitor in the form of recombinant or purified C1
inhibitor or agents interfering with proteins involved in bradykinin generation
or the bradykinin B2 receptor.
It is getting a bit crowded, but there still is
room for improvement to achieve the goal set by the HAE community: a life free from disease.
Intellia’s NTLA-2002, a one-time CRISPR Cas9 therapeutic now in phase 3,
achieves a 80-90% attack rate reduction by destroying prekallikrein gene
activity. The efficacy is in line with competing therapeutics that need to be
taken indefinitely and cost around half a million USD- annually.
A good estimate
for the price of NTLA-2002 would be $3M, meaning that after 6 years this
convenient treatment would start saving the healthcare system serious money for
a disease that gets diagnosed typically in the late teens or early 20s.
Nevertheless, the financial market could not be less excited by NTLA-2002 as
indicated by the lackluster response to its clinical data. In theory, NTLA-2002
could treat every HAE patient and rake in $30B in the process. Compare that to
the annual $5B and growing market for the traditional forever treatment options
which will cost the system $60B plus over the next 10 years alone…without even
treating every patient and leaving treatment gaps due to insurance that like to
drag their feet.
We are talking here about cost alone, not even how a one-time
treatment would benefit a HAE patient: less stress, both financial and emotional
which in itself is a major risk factor for HAE attacks. Considering the lack of
investor interest in NTLA-2002, I concluded that going from 80-90% attack rate
reduction to 100% attack rate reduction following a one-time treatment, is not
worth the time and financial risk. Disclosing the idea also does not make sense
since it would destroy any IP value if the idea was picked by somebody else or
conceived independently, further reducing chances it would ever get to patients.
Just recently, Pfizer, a major player in hemophilia therapeutics, declined to
bring a reasonably effective and safe hemophilia A one-time gene therapy
discovered by Sangamo to market. Again, I ask myself, why would Pfizer ever want
to destroy a lucrative market it participates in? I can only see how an outside
company would want to disrupt such a rare disease market (hemophilia is bigger
than HAE, so that situation could actually happen e.g. in the form of
Regeneron).
What about patients? I am slowly coming to accept that the
best possible treatment for a disease will often not be the end-game in terms of
therapeutic development. Sometimes it is pharma’s profit model, sometimes
society that does not feel that a patient deserves better. Take for example a
rich country like Singapore where patients do not have access to modern HAE
medicines and where even women are still treated with the androgen sledgehammer.
It seems we have arrived at a turning point where it has become hard to invest
in best possible therapeutics in a resource-constrained environment where money
gets diverted to the military and AI. Making matters worse for rare disease drug
development, as international ties continue to deteriorate, the target
population becomes even smaller.
No comments:
Post a Comment