Lecture #10 Flashcards
Mutations in PCSK9 gene causes
autosomal dominant hypercholesterolemia
these pts with hypercholesterolemia carry gain-of-function PCSK9 variants
want desirable value of LDL < 130 mg/dL
Individuals with PCSK9 nonsense mutations
are extremely healthy
loss of function stop codon mutation
increase in PCSK9
leads to a decrease in LDL-R proteins –> increase in LDL-C
Blocking PCSK9
use a fully human monoclonal antibody against PCSK9 to block the PCSK9/LDL-R interaction
LDL-R recycling is restored, increased LDL-R concentration
PCSK9 failed to be
a blockbuster drug because it is only used for a very narrow pt population
also extremely high cost
The basics of biotech valuation
company value = drug value = drug’s commercial potential
Drug’s commercial potential
–> revenue forcasting –> peak sale + years of peak sales
Discounted cash flow analysis
–> future cash flows * time value of money = total value of drug
Stock price
–> total value of company/total shares outstanding
Future money is always
less than past/current money
Key points to consider for drug value evaluation
does this new drug offer any advantage compared to existing drugs?
where does this drug fit in the treatment paradigm of the unmet medical need? which pt population would use this drug and at which point during their treatment?
what data should clincial trials show to secure FDA approval and commerical success?
how to set the price of the drug so that payers would be willing to pay?
Problems associated with cardiovascular drug (or in general non-cancer drug) development
trials may have to be very long and need many thousands of pts
safety profile of the drug needs to be excellent
alternative endpoint may not be accepted; lowering LDL (short) vs reductions in atherosclerotic cardiovascular events (medium), or reducing mortality (extremely long)
may only get approved for a very narrow pt population
compete with many existing widely used drugs
biologics might be signigicantly more expensive than small molecules and payers may not want to pay