Genomics Is And Will Be A Transformational Megatrend In Medical Care But The Path to Targeted Drugs Will Be Rocky At Best
Posted Apr 24 2012 12:00am
Medical Megatrends – Genomics Part III
Genomics promises to fundamentally change much of medical
care as described in the two prior posts on this subject. But the ultimate value of this new
understanding of basic human biology will in many cases come with fits and
starts. The saga of belimumab (Benlysta) and Human Genome Sciences is
Systemic lupus erythematosus (SLE) occurs in somewhere
between 300,000 and 4 million Americans according to the Centers for Disease Control.
It is more common in women than men and more common in African Americans than
Caucasians. SLE is an autoimmune disease of unknown etiology which can affect
many body organs and systems and can lead to death. The disease can wax and
wane and can flare with activity in the central nervous system and the kidneys.
Genomic studies done by Human Genome Sciences (HGS) more than a decade ago
showed that it might be possible to create a monoclonal antibody to react
against the B lymphocyte stimulator, a cytokine that has been found to
correlate with activity in SLE.
produced the monoclonal antibody – belimumab – and then conducted the required
preclinical studies in test tubes and animals to demonstrate its activity and
toxicities. With FDA approval it then conducted phase 1 and 2 studies in humans
to determine toxicities, side effects and early suggestions of activity in humans.
It then proceeded to complete two double blind randomized controlled trials
comparing standard treatment to standard treatment plus belimumab in 1684
patients. The results were sufficient to win a 13 to 2 recommendation vote from
the FDA’s advisory panel in November, 2010. The FDA announced its approval and
the required package labeling in March, 2011. The FDA and HGS have both noted
that this is the first new drug for SLE in 50 years and the approval was lauded
by the Lupus Foundation of America. The intravenously administered drug is
available for about $35-40,000 per year.
sounds straight forward – good science led to a new drug that should benefit
many patients who have had limited treatment choices until now. But for HGS it
has been a rocky road at best over the years. Founded in 1992, the company set
out to use genomic discoveries to create new pharmaceuticals. By 2000, it was
being hailed as an up and coming company and it stock price rose to over $100
per share. But the share price then plummeted along with those of other
genomic-oriented companies. Fortunately for HGS, its CEO, Dr William Haseltine,
made use of the high stock price to lock in a soon to be much needed cash
stockpile. The company’s first drug candidate – to treat leg ulcers – met with
failure and was dropped. A second drug – for hepatitis C- looked to be very
promising and carried the hopes of staff and investors but a key trial was
unsuccessful and HGS ultimately had to make the decision to pull the plug on
this drug candidate as well – after expending many millions of dollars in the
preclinical- and clinical testing phases. The stock price dropped to a low of
52 cents per share and the cash war chest was running lower and lower. Then –
finally – came good news with the two belimumab patient studies and the stock
price jumped immediately but to no where near the heights of a decade before.
And then the drug did not “take
off” as fast as Wall Street had predicted (nor as HGS would have preferred) and
the stock price fell back to about $7 per share. But Glaxo which markets the
drug for HGS and has contractual arrangements for other HGS compounds in the
pipeline has just offered about $14 per share to acquire the company. HGS has
said “no thanks” but the story is probably not over yet.
looks to be a useful addition to the SLE treatment armamentarium. But there are
questions and critics. SLE is much more common in African Americans but the two
patient trials had relatively few blacks enrolled and there was some suggestion
that perhaps they responded less well. The drug is also not without potential
side effects including predisposing to serious infection. Further, some
calculate that it will take about four (or more) patients treated to lead to
one patient benefitting. At $35,000 per patient per year, that means a total expenditure
of about $140,000 or more to benefit that one patient.
is that genomics is and will be a transformational megatrend in medical care as
I discussed in The Future of Medicine –
Megatrends in Healthcare . . But “targeted” therapy is not always all that
narrowly targeted in a way that either is effective for all nor is the drug
necessarily side effect free – and it may be quite expensive. The story of Human
Genome Sciences demonstrates that the path from a genomic discovery in the laboratory
to a marketed drug can be long, expensive and fraught with many disappointments
along the way. But conversely, innovation
as demonstrated here is and will be the lifeblood of continued future success
and improved human health.