The price of life
The most expensive drugs currently being used
in medicine tend to be for childhood rare diseases or cancer. The most costly
drug on the market was Glybera, priced at 1 million euros. However, just one
patient was treated, and the drug was pulled after 5 years because of lack of
sales. In the cancer field, potentially curative immunotherapies are being used
at costs ranging from 200 000 – 400 000 euros. Thus, the price of a
human life appears to be between 400 000 and 1 million euros in developed
societies.
Life was
cheap
Looking at
human history, and especially the 20th century, the value of human life has not
been much. The list of mass killers is long. Topping many lists is Mao Zedong,
who caused the death of up to 70 million of his compatriots. Joseph Stalin
comes in as a good second with up to 60 million of his own killed. Hitler and
his henchmen killed up to 30 million civilians.
Regimes that
killed millions include the Nationalist government of China, the Imperial
Japanese army, the private forces of Leopold II in Kongo, Ranavalona I of
Madagascar (the only woman on the list, and quite an interesting story), the
Khmer Rouge in Cambodia, and the serial holocausts in the Ottoman empire. Less
well documented murderers include Genghis Khan and Timur Lenk, who probably
killed tens of millions each. Then there are of course various wars and
conquests, where tens of millions died. Thus, historically, the price of life
has been minimal.
After
reaching its highest mark in the mid 20th century, the
self-destructive nature of humanity seems to have petered out. Ruanda, Burundi,
Darfur, East Timor and Yugoslavia remind us that it can still happen, but in
general less people have been purposefully slain in the Nuclear Age.
Value of
life increases
In
developed countries, the value of life and the individual has been increasing
in the past 50 years. From a philosophical point of view, this could relate to
increasing secularism. If there is only one life, and no afterlife or rebirth, life
starts to seem more valuable. The random mass killers of the past - war, infant
mortality, childbirth, pandemics, epidemics, tuberculosis, plague and smallpox
- are no longer common. Thus, the general feeling of safety has increased, and
premature death has become perceived as unfair.
A luxury
product
Together
with a strong increase in the general wealth of humanity, especially in
developed nations, there have been more resources available for medical
research. Historically, scientific medicine (as opposed to “natural” or
spiritual healing) has basically been a luxury product, which becomes
affordable only after more basic needs have been met. Food, shelter, family,
war and religion have taken priority. In the last 50 years, apparently these
basic needs have been met to such degree, that there has been money left over for
science.
In Europe medicine
made some progress in antiquity, and some of this knowledge was retained in the
Middle East during the Common Era. The Middle Ages constituted big steps
backwards in medicine. All diseases were punishments from God, mediated by
imbalances in the “humors”: blood, yellow bile, black bile and phlegm. Beyond
prayer, basically the only treatment was venesection, letting of blood from the
vein.
Scientific
medicine
Things
started to slowly improve in the 18th century, when microbes,
anatomy and physiology started to be understood. However, the speed of development accelerated
dramatically after World War 2. Although development continues to be rapid,
heretofore the new millennium has been characterized by a high degree of
regulation and dramatic increases in the bureaucracy of clinical trials.
Consequently, academic clinical research with new drugs has ended in most of
the world, as only companies can afford to pay for trials. Even for companies,
the cost of trials has skyrocketed, correlating with prominent increases in the
price of drugs approved (Hemminki A).
Too
expensive drugs
The new
millennium has seen unfortunate cases of effective drugs not being used because
of cost. An illustrative example is Glybera (lipogene tiparvovec). This gene
therapy was well tolerated and quite effective in treating a hereditary
deficiency of lipoprotein lipase. This rare but deadly disease affects about
one in million children. Both rarity and the patient population complicate
clinical studies.
Two small
trials were nevertheless performed, resulting in eventual approval by the
European Medicines Agency.
The initial company (AMT) went bankrupt while the
regulators were prevaricating. A new company, UniQure, picked up the drug (and
AMT’s debts), and took it to the market. The drug was priced at circa 1 million
euros, and apparently, only one patient was treated outside of trials. Eventually,
the company did not renew the marketing approval, due to lack of sales. In the
5 years the drug was available, an estimated 25-50 patients could have been
treated in Europe, in a potentially curative manner. Therefore, it is clear
that the drug was not being used because of the high price.
Thus, this
suggests that the price of life is less than 1 million euros.
Affordable
expensive drugs
How about
some successful examples. Soliris is a monoclonal antibody effective is certain
rare diseases. It is priced at 700 000 $/year. Most hyper-expensive drugs
are recombinant proteins used for enzyme replacement treatment of hereditary
enzyme deficiencies. Examples include Elaprase (500 000 $/year), Naglazyme
(365 000 $/year) and Cinryze (350 000 $/year).
There are
also some conventional-sounding approaches which have been priced quite highly,
because their indication is for rare (“orphan”) diseases. Some examples include
Folotyn (360 000 $/year), a variant of an old chemotherapeutic, and Acthar
(200 000 $/year), a conventional hormonal product. The latter has been a
subject of recent controversy due to its 100 000% price increase in a
monopoly situation.
In the
cancer field, the dogma used to be that new drugs can cost around 50 000€
per quality adjusted life year. Higher than that would frequently result in
negative cost-benefit analysis in evaluations such as performed by UK National
Institute for Health and Care Excellence NICE. Thus, one can interpret that the
value of life used to be around 50 000€/ year.
Cancer
immunotherapy
The 50 000€ dogma
has apparently changed in recent years, with the advent of cancer immunotherapy.
Checkpoint inhibitors such as pembrolizumab, nivolumab, ipilimumab, etc, can
cost upwards of 200 000€ per patient. CAR-T cell therapies Kymriah and
Yescarta are priced between 300 000 – 400 000€. CAR-T is a treatment
resulting in high cure rates, and in the US they have an interesting
pay-for-performance pricing model, where the company returns the payment if
there is no efficacy at one month. Probably the price of these drugs has something
to do with the fact the only comparative treatment is bone marrow
transplantation, which costs around half a million on average and is less
effective and more toxic than CAR-T.
Curative
drugs fetch a higher price
A common
denominator for the most expensive cancer drugs is their curative potential,
which apparently allows for higher pricing than with effective, but not
curative treatments. Although one denominator of drug pricing is the cost of
clinical trials (Hemminki A), and production costs obviously have nothing to do
with price, it is clear that for-profit companies will charge what they can,
according to the rules of the market economy. For-profit companies cannot
determine humanitarian values, only society can.
Some but
not all of these drugs mentioned above are available in most developed
countries. Prices tend to be similar, although somewhat higher in the US. Since
payers are prepared to pay up to 400 000€ for potentially curative drugs,
but not up to 1 million euros (Glybera), the price of life is somewhere between
these numbers.
Summary
Fortunately
for patients, but unfortunately for payers, there will be many more expensive
drugs in the near future. Moreover, in the cancer field, combination
immunotherapy will increase the overall costs of care. If and when new drugs
enter the market at prices between 400 000 – 1 million, the exact price of
life can be determined more accurately.
Akseli
Hemminki, MD, PhD, eMBA
Professor
of Oncology
Hemminki A.
Crossing the Valley of Death with Advanced Therapy. Published by Nomerta,
Turku, Finland, 2015. Available at http://www.nomerta.net and several e-book
stores globally
