Now that 2012 is drawing to a close, it’s once again time to take a look back at a year that saw some big hits and misses for the biotech industry – and there were plenty of both!

1. Big Wins, a Cliff, a
Race and a Red
Face: A 2012
Recap
Jennifer Boggs
Managing Editor BioWorld
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2. • Now that 2012 is drawing to a close, it’s once again time to take a
look back at a year that saw some big hits and misses for the
biotech industry – and there were plenty of both. The hits saw
some big drug approvals – some of those well in advance of
PDUFA dates, which, hopefully, is a good sign that the FDA is
willing to accelerate approvals in areas of high unmet need – and
major clinical advances in areas such as hepatitis C, while the
misses included disappointing data and some stark realities facing
big pharma firms.
• The year also saw lawmakers get into the bipartisan spirit, passing
both FDASIA and the JOBS Act. As we head into 2013, it will be
interesting to see how those regulatory additions – such as
the GAIN legislation aimed at giving antibiotic developers a leg up
and the provision allowing for small firms to consider going public
as an emerging growth company – may affect the industry.
• But first, let’s take a look at some of the notable stories and trends
in biopharma over the past 12 months.
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3. • After striking out at the FDA over the past two years, two of the
big three obesity drugs won approval in 2012. Vivus Inc.’s Qsymia
(phentermine/topiramate) and Arena Pharmaceuticals
Inc.’s Belviq (lorcaserin) hit the market. It’s too early to judge
market uptake – though analysts have been monitoring Qsymia’s
launch on a weekly basis – but the approvals are at the very least
a sign that the FDA is considering obesity a serious health
concern and those first two nods could pave the way for more
obesity drug approvals in the future.
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4. • While Qsymia and Belviq topped the most exciting approvals in
2012, according to BioWorld’s informal poll, the year was full of
other FDA nods. Irritable bowel syndrome drug Linzess came in
second in the BioWorld poll, followed by cystic fibrosis
drug Kalydeco, prostate cancer treatment Xtandi and recently
approved medullary thyroid cancer drug Cometriq. But plenty of
other drugs easily could have made the list – Stribald, formerly
known as Btripla, for HIV; Bydureon’s hard-won approval in Type
II diabetes; Erivedge, the first hedgehog inhibitor to reach
market; Aubagio for multiple sclerosis; cancer
drug Kyprolis; Lucentis’ approval as the first new drug for diabetic
macular edema in more than 50 years; and Ariad
Pharmaceuticals Inc.’s Iclusig (which, at three months ahead of
its PDUFA date, came in just under the wire to make the 2012
list.)
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5. • But no approval in 2012 proved a bigger triumph than Glybera, the
first gene therapy to (finally) gain approval. After some back and
forth at the European Medicines Agency (EMA) and its Committee
for Medicinal Products for Human Use (CHMP), the CHMP awarded
a positive recommendation in July, followed by the EMA’s official
stamp of approval in November. It wasn’t easy; the drawn-out
process drove developer Amsterdam Molecular Therapeutics
into bankruptcy, forcing it to divest Glybera into newly formed private
company uniQure BV. But the approval marks not only a big win for
the gene therapy space, it also signals a change in the at least
European regulators assess clinical benefit in rare diseases, given
that application for Glybera included data from a mere 27 patients.
The advent of gene therapy, a one-off treatment vs. the typical daily
or weekly administration, in the marketplace also stands to change
reimbursement policies in order to accommodate those types of
long-term treatment options.1-800-477-6307 or 404-262-5476
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6. • At last year’s JP Morgan conference, Bristol-Myers Squibb Co.’s
execs couldn’t help gloating over their $2.5 billion acquisition of
Inhibitex Inc. After all, it was hardly the whopping $11 billion Gilead
Sciences Inc. paid for fellow hepatitis C virus (HCV) drug developer
Pharmasset Inc., a price many analysts at the time considered much
too high, particularly considering the growing competition to get an
all-oral HCV regimen to market.
• But a big mushroom cloud appeared over the space during the
summer, and when the dust settled, BMS was pretty much out of the
picture, having discontinued its nucleoside HCV drug due to toxicity
issues. The news also affected other “nuc” programs, most notably
Idenix Pharmaceuticals Inc.’s IDX19368, which was placed on clinical
hold. Meanwhile, positive data just kept coming for Gilead, which is
entering 2013 easily poised as one the lead contenders for an all-oral
regimen.
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7. • The HCV space was advancing like gangbusters, but other areas
were not so fortunate in 2012. With all the Phase III readouts, drugs
targeting Alzheimer’s disease could have been the year’s top success
story; Instead, detractors of the amyloid-beta theory gained
ammunition in the ongoing amyloid-beta-vs.-tau battle. First, there
was the Phase III implosion of bapineuzumab – the headline
in BioWorld Today said it all: “J&J-Pfizer’s Alzheimer’s Drug Crashes,
Burns in Phase III.” That news was promptly followed by the Phase III
miss of Eli Lilly and Co.’s solanezumab, though Lilly isn’t ready to
admit defeat yet. Those failures, however, came as no surprise to
those who fall on the tau tangle side of the Alzheimer’s
argument. TauRx Therapeutics Inc.’s Claude Wischik even told
BioWorld in November that it never made “any sense to us that
people think going after amyloid” would make a dent in the disease.
(continued on next slide)
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8. • TauRx is putting the tau theory to the test, getting ready to launch
a Phase III program testing tau aggregation inhibitor LMTX,
though we likely won’t see any data before 2015.
• In the meantime, the case for amyloid-beta seems to be taking its
cues from Monty Python – it’s not dead yet. A November talk at
the National Institutes of Health had Harvard University’s Jie
Shen discussing early stage research concluding that amyloid-
beta definitely has “something to do with the pathogenesis of
Alzheimer’s disease.” So it looks like the debate is destined to go
on to see whether amyloid-beta, tau or a newer Alzheimer’s target
might become the Holy Grail in biopharma’s ongoing efforts to
treat the devastating neurodegenerative disease.
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9. • While politicians spent the last few months of the year sounding off
about the so-called fiscal cliff, big pharma finally found itself standing
at the edge of its own sheer drop in 2012, staring down into the
abyss of lost profits. After years of predictions from industry experts,
pharma firms finally started to feel the initial impact as once-
blockbuster products began smashing upon the rocks. Pfizer Inc., for
instance, saw a 19 percent cut in first-quarter profits stemming from
the patent expiration for top-selling cholesterol drug Lipitorand in
September saw its credit rating downgraded by Fitch. And it wasn’t
alone. AstraZeneca plc’s CEO David Brennan stepped down in April
amid shareholder pressure as the London-based big pharma
reported staggering drops in sales thanks to generic competition to
products such as Nexium (esomeprazole) and Merrem
(meropenem). (Continued on next slide)
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10. • And, on the eve of reporting its third-quarter earnings, Eli Lilly and
Co. saw its own ratings lowered by Fitch, which called Lilly’s
looming patent cliff “the steepest in the industry,” citing potential
losses of antidepressant Cymbalta (duloxetine) and Type I
diabetes drug Humalog (lispro) coming next year.
• The good news is that, as the threats to its bottom line
materialized, big pharma seemed much more willing to try new
strategies. The past year saw the industry employ some new and
interesting approaches to ramping up drug development – the
launch of Transcelerate BioPharma Inc. is a good example, along
with the rise in academic partnerships such as GSK’s December
deal with MD Anderson. Perhaps if big pharmas can find more
ways to foster innovation, they won’t end up in the Pit of Despair.
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11. • If you’re going to present stellar clinical data, you’d better make
sure those results are accurate. Vertex Pharmaceuticals
Inc. learned that lesson in May when it revealed that its previously
reported Phase II results for the cystic fibrosis combination of
Kalydeco plus VX-809 were a little off the mark: Instead of 46
percent of patients showing improved lung function, the actual
results were 35 percent. That 11 percent disparity sent shares of
Vertex sinking 10 percent that day.
• But that turned out to be nothing compared to Peregrine
Pharmaceuticals Inc.’s gaffe a few months later. In what has to be
the Biggest Oops for 2012, execs of the Tustin, Calif.-based firm
found themselves choking down a few mouthfuls of crow after they
had to return to investors with the admission that the survival data
from the much-lauded Phase IIb lung cancer trial of bavituximab
might not have been so impressive after all. (Continued on next 11
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slide)

12. • The company cited “major discrepancies” in the findings, which it
attributed to an independent third party contracted to code and
distribute investigational drug product. Peregrine launched an
investigation to determine the extent of the data disparity and,
while that investigation is still ongoing, the company’s shares –
and perhaps, credibility – have yet to fully recover. To add insult to
injury, Peregrine shortly after received a default notice for the $15
million in initial funding under a $30 million term loan, due to the
data discrepancies, though the company managed to scrape
together $14.3 million in an at-market agreement to replace that
funding.
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13. Originally published in BioWorld Perspectives, on Dec. 21, 2012.
http://bioworld.blogs.bioworld.com/
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