ANALYZING AND FORECASTING THE FUSION PROTEIN MARKET AND PIPELINE - Fusion Protein Technologies for Biopharmaceuticals: Applications and Challenges - page 31

this section focuses on ophta lmologic al indi cations of for Avast in patient s and 19% for Lucentis patient s. Further-

more, there have been repor ts that patient s taking Avastin
may be at a grea ter ris k than Lu centis for wet AMD due to
(1) the Fc com ponent and correspo nding highe r protein
content , and (2) potenti al contam ination of an Avastin lot
[38]. Toget her, these factor s may restri ct use of cheap er
Avastin, theref ore, it seems likely that new wet AMD drugs
will continue to target Lu centis rather than Avast in.
Regeneron and Bayer sta rted a Phase III develop ment
program for VEG F trap-Eye in wet AMD in Augu st 2007,
which involved two Ph ase III trials (“View 1” and “View 2”)
compari ng VEGF trap-Eye with Lu centis. Data reporte d in
November 2010 [39] for View 1 indicated that vision was
maintai ned or im proved in 96% patients receiving monthly
afliberce pt and 95% o f thos e receiving a dose o nce or twic e a
month, versus 94% patient s receiving monthly Lucentis.
Very simi lar resu lts were maint ained in patients taking each
drug after 1 year in the View 2 trial. Both drugs wer e
reporte d to have similar side effects. Import antly, thes e
data indi cate that VEGF trap-Eye could be dosed less
frequent ly than Lucentis [40] . Lower adm inistratio n fre-
quency is a key driver for wet AMD drugs and is thoug ht to
be anot her factor driving up off-labe l use of Avast in in wet
AMD (as Avastin is thoug ht to remai n in the eye longe r
than Lucent is, potential ly mean ing lower-frequency admin-
istratio n 28 ). However, we flag that pricin g is also likel y to be
an important factor in the uptake of the VEGF trap-Eye,
particu larly for drugs showing similar efficacy.
In summa ry, given simi lar effica cy and safety View 1 and
2 data, we thi nk that Lu centis is VEG F trap-Eye 's key
compet itor, and independe nt market analyst s have indicat ed
that they believe these two drugs will be the leaders of the
wet AMD market by 2013 [41] and that there are few
differentiator s betwee n the drugs. However, we als o think
that off-label Avastin also represents a competitor, given its
low-cost nature in wet AMD, similar efficacy to Lucentis,
and the fact that it is thought to stay in the eye longer than
Lucentis, potentially allowing for less-frequent dosing.
However, the extent of this threat may have been lessened
by the safety data from CATT, together potentially with any
red flags during the generation of future safety data with
greater patient usage.

Afliber cept (or VEG F trap-Eye).
Wet AMD is a leading cause of blindnes s in elderly
patients. In the United Stat es, it has been estimated that
1.6 milli on peopl e over 50 have wet AM D and there are

500,000
new cases of wet AMD are diagnosed annual ly wor ldwide
[34]. Wet AMD is caused by abnorma l neovascular isation
(angioge nesis), leading to the gener ation of lea ky vessels
behind the retina growing under the macula . Following
approval in 2000, the standar d of wet AM D care was
Novartis/QLT's Visud yne 1 (verteporfin/photodyn amic
therapy), pri or to any biolo gic therapies approved for the
indicati on. Visudyne works by causing localize d endot helial
cell dest ruction lea ding to occlusion o f leaking blood ves-
sels. Then, in Decem ber 2004, the FDA approved Eyetech
Pharmac euticals' Macu gen 1 (pegaptanib). Th is nucleic
acid therapeutic belongs to the aptame r drug class, and it
functioned by inhibi ting the interaction of VEG F with
VEGF receptors (V EGF is a positive regulator of angi ogen-
esis [35] ). In 2003, the year before Macugen was approved,
Visud yne gener ated $35 7 milli on, but by 2010, sales were
$91 mill ion.
In June 2006, the FDA approved Roc he/Novartis 's
Lucentis 1 (ranibi zumab): a huma nized IgG1 kappa mAb
antibody fragme nt that binds to multipl e VEGF-A isoforms.
The drug was approved in Europe in Janua ry 2007, and
annual sal es by 2010 were $3.1 billion. 26 OSI Pharmac eut-
icals (Ma cugen's earlier owner) repor ted Macu gen sales
in 2006 of $107 milli on, but by 2008, annual sal es were
<

20 0,000 new case s diagnosed each year, while

$1 2 milli on. Roche' s Avastin 1 , an anti-V EGF mAb
approved to tre at a range of cancers, is clos ely relat ed to
Lucentis and it has been used off-labe l to treat wet AM D.
Avastin use has been driven by the b ig price difference s per
treatme nt, it has been repor ted that Lucent is costs

$2000,

while Avastin costs $50 [36] . A number of U.S. agenc ies

and bodie s includi ng the FDA, the NIH, CMS (Cent ers for
Medicare & Medicaid Servi ces), and the Senat e Sp ecial
Committ ee on Age ing have been involved in discussions
over whe ther Avastin off-labe l could be an effective substi-
tute for Lucent is, given the substantia l cost-savings possible
[37]. To help answer this questio n, the National Eye Insti-
tute-sponso red head- to-head CATT (comparis on of AM D
treatme nts trials) trial comparing Lucentis with Avastin was
initiated in 2008. In April 2011, this trial reporte d results
showing that Avastin and Lucentis are equally effective in
treating age-relat ed mac ular degeneration, in ter ms of visu al
acuity improvemen t and gain or loss in visu al function. 27
However, the inciden ce of serious adverse events was 24 %

2.4 PIPELINE DATABASE ANALYSIS

Analysis of our FP database, which includes 43 FPs in Phase
II and above clinical development (including FPs on the
market) yields two main findings: (1) the most common
therapy area target is oncology, followed by autoimmune,
and (2) many Big Pharma/Big Biotech companies have at
least one FP in development. However, few have more than

26 Novartis reported 2010 ex-U.S. sales of $1533 million, while Roche
reported 2010 U.S. sales of $1565 million (based on exchange rates as of
December 31, 2010).
27 http://www.nih.gov/news/health/apr2011/nei-28.htm 28 http://www.nei.nih.gov/news/pressreleases/022208.asp