The Other Side of Drug Discovery, Part 2
By Jason Socrates
Bardi
In
"The Other Side of Drug
Discovery, Part 1", TSRI investigator Tamas Bartfai says,
"If you make a truly original drug that has a health benefit,
people will eventually buy it."
However,
drug design is not all wine and roses.
Drug development is the single most regulated human activity.
The mandate of the FDA is to protect the public against dangerous
drugs, and they do this in a variety of ways, including monitoring
approved drugs on the market for unexpected health consequences,
reviewing drug applications, and mandating full disclosure
in drug labels and advertisements.
Nevertheless, regulation limits the number of drugs that
companies can bring on the market, and forces the pharmaceutical
companies to make tough choices. Often these choices involve
research and development, which sometimes directly affects
investigators at universities and institutions like TSRI who
partner and collaborate with scientists in industry.
Bringing a drug from the test tube to the prescription bottle
costs in excess of $500 million on the average. The amount
of this spent on initial research and development may be miniscule
by comparison with the clinical trials and the marketing expenses—perhaps
only 1.5-5.0 percent of the total.
"The marketing costs, for instance," says Bartfai, "are
usually 15 to 20 times the cost of researching the drug."
For the most part, basic research is blind to this sort
of decision making because an equal amount of science goes
into making a small drugs and big drugs. "With equal ingenuity,
you can make a drug that will sell for $100 million or one
that will sell for $100 billion by the end of its lifetime,"
says Bartfai.
But when companies are selecting drug candidates for the
proverbial $500 million check, they make sure that the candidates
make good economic sense. A new anti-epileptic, for instance,
poses formidable economic challenges because of difficulty
testing it. "If you cannot figure out how a drug can be tested,
you cannot make the drug," says Bartfai.
Consider that there are three types of epilepsy patients:
those who are not yet diagnosed and therefore not taking medication;
those who are diagnosed and currently taking approved medications;
and those who are diagnosed but who are resistant to current
medicines.
The best population in which to test a new drug would be
newly diagnosed patients, but one would have an uphill battle
overcoming doctors' bias towards existing drugs. Why would
a doctor put a patient on an experimental drug when there
are others that seem to work just fine? One would need an
extraordinary amount of data suggesting that the new compound
is significantly better.
And anyone who is currently taking an anti-epilepsy drug
and doing just fine would not stop to take a new, experimental
drug and risk having a seizure. Nor would a doctor recommend
an experimental drug to a patient who is responding well to
an approved one.
That leaves only the group of people who are resistant to
all existing anti-epileptic drugs, who would not be the best
test population
"Is a new anti-epilepsy drug a great discovery?" asks Bartfai.
"Yes. But does it have great commercial value? No."
"If you want to make a drug that acts on the brain," he
adds, "if, then the marketing and clinical development departments
will suggest you make a drug for Alzheimer's disease."
Commercial Accessibility
People will only switch to a new drug if the new drug is
substantially better—for instance if it is 10 times more
powerful, if it can be taken orally rather than injected,
or taken once a day as opposed to once every four hours.
In the same vein, there are many drugs that fail because
of their side effects, despite the fact that they actually
work very well. For instance fat absorption blockers should
be a raging success story in the United States, where according
to Center for Disease Control and Prevention (CDC) estimates,
nearly a third of the adult population is obese. These drugs
should allow people to literally have their cake and eat it,
but they are one of the failures in the annals of drug design,
because they prevent the absorption of fat with the undesirable
side effect of causing diarrhea.
However, says Bartfai, if a new drug were to be invented
that had the same effect without these side effects, it would
be a huge success.
In addition to toxicity, bioavailability, synthesis, and
efficacy, a potential drug's commercial accessibility makes
a big difference to pharmaceutical companies. Doctors will
choose whatever drugs they know to treat the symptoms they
see, and if there is not a compelling reason to switch to
a new drug, they won't.
"The rule of thumb is that any physician can remember three
drugs for any set of symptoms," says Bartfai. "If there are
17 drugs in your category, and you are not in the top three,
then forget it." That makes marketing the decisive factor
for success of the Pharma companies.
Novel compounds that elicit an existing effect may not be
worth the effort of developing into a licensed and approved
drug.
"Once you make a human heart beta-receptor and a slightly
better one and a slightly better one, there's not much left,"
says Bartfai. "People buy an effect—they don't buy a
new mechanism. No physician or patient is convinced by a new
mechanism."
All of this adds up to a drug development landscape that
is pock-marked with pitfalls and chasms that can derail a
potential drug's success even after it has emerged as a highly
successful candidate. Communicating how to navigate this landscape
is one of Bartfai's goals for the lectures.
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