Biomedical Engineering Reference
In-Depth Information
device for subcutane ous (SC) adm inistratio n, which is well
establish ed in the market and convenient for patients; (4)
favorable formul ary sta tus at leading U.S. heal th insurers,
further help ed by benefic ial formul ary tier placing often
granted to self-ad ministered biologi cs [8]; and (5) Enbrel
has sign ificantly less do se escalati on than com petitors
such as Abbo tt/Eisai's mAb Hum ira (adalimu mab) o r
J&J/Merc k/Mitsubi shi Tanabe's mAb Remicad e (inflixi-
mab) [9]. Dose escalation requires increasing dosage siz es
to overcome neut ralizing antibodies , which boosts treatme nt
costs; theref ore, Enbrel 's lack of dose escalati on is a posi tive
aspect for patient treat ment if physici ans are concerned
about this iss ue.
However, we think En brel sales have reached the mature
stage of sales tra jectory, with the resu lt that we think sal es
will be low growth in the near term, befor e beginning to
slowl y decline, based on our belief that there are few near-
term sign ificant po sitive catal ysts to boost sales growth : (1)
market penet ration has been subst antial but has now slowed
as Enbrel reac hes peak penetra tion of its key markets; (2)
although Enbrel is in clinical trials for addi tional indi cations
(e.g., Phase III trials for graft vs. host rejecti on [10] ), we do
not see any n ew indicati on expansions driving substant ially
greater sal es for two reasons: we thin k there is already
extensive off-label pres cription of Enbrel,
9
and we think
that the drug already has approval for the indicati ons that
generat e strong sales; (3) weekly or twice wee kly dosing is a
disadvanta ge compare d to othe r biologics for import ant
indicati ons such as RA and psorias is, whe re most dosing
of compet itor biologi cs is fortni ghtly, month ly, or less
frequent; (4) going forward, newer agent s both in late-stage
clinical develop ment and those that h ave been recently
launched represent significan t threats, due to strong market -
ing and improved profil es in terms of safety, effica cy,
administ ration (inclu ding dosing frequency), and/or novel
mechanism of act ion; and (5) we expect sales decline to
increase after 2014/15 whe n we think the first bios imilars
may appea r o n the market. However, we expect bios imilar
erosion of brand ed Enbrel to be substant ially less aggre ssive
(in terms of speed and perc entage cannibaliz ation of the
branded originator drug) than small molecu le generic ero-
sion for three reasons. First, we expect there to be a lower
price different ial betwee n the brand ed origina tor drug and
the b iosimilar (we expect a 15-30% price differ ence).
Second, we also think there will be lower com petition in
the biosimilar market, as we think there will be fewer
biosimilar s developers (given the costs and investment
required— particularl y in building manufac turing and reg u-
latory functions) . Last, we think phy sicians will rem ain wary
of swa pping a brand ed drug with substant ial safe ty and
efficacy data for a slight ly cheap er bios imilar with compar-
atively little safe ty and effica cy d ata.
2.3.2 Ore ncia
Bristol -Myers Squib's (BMS) Orenci a (abatacept ) is an FP
compri sed the extracellular domain of human CTLA4
(Cyto toxic T-Lymph ocyte Antig en 4) and the IgG 1 Fc
region, whi ch is approved for the treatme nt of adul t rheu-
matoid arthritis (RA) and juvenile idiopathi c arthri tis (JIA).
It was approved in the Unite d Stat es in Decem ber 2005 and
in Europe in May 2007.
We thin k the mos t important posi tive factors set to drive
up Orencia sales are the drug's poten tial to move into the
TNF inhibi tor (TNFi) marketspa ce, and the successf ul
potenti al launch of a subcutane ous administ ration. RA bio-
logics are broad ly split into those targeting TNF and thos e
with other targets. TNFis such as En brel have domi nated the
autoim mune biologics market since their laun ch, and
the most popul ar RA drugs —Enbrel and Humira— are
both TNFi s. Non-TN Fi biologi cs such as Or encia have
been held back by U.S. labe ls that require rheumatol ogists
to treat with TNFi s befor e thes e drugs can be used. As a
result, these therapi es have tend ed to be used in third line
[11]. However, in July 2010, Orencia' s Eu ropean label was
expanded to include patient s who had inad equately
respon ded to DMARD (di sease-modi fying antirheum atic
drug) therapi es, which opens up the secon d-line market
for g reater penetra tion.
10
We believe the secon d major
positive driver of Or encia sales growth will be the potential
approval o f a subcutane ous form, given that most of the
drug's compet itors are in this easier-to-use form. A self-
admini stered subcutane ous formulat ion often has mor e
favorable formular y plac ing [8]. This was subm itted to
the FDA in Octobe r 2010, so we expect an FDA decision
on this in H2-2011,
11
and we could see launch soon after if
there is a positive FDA response.
Orencia has also been in late-sta ge clini cal trials to treat
gastroi ntestinal (GI) autoimm une dise ases. However, the
drug failed to mee t its primary endpoin t in both Crohn' s
disease [12] and ulcerative colitis [13] . BM S has also
terminat ed earli er-stage clini cal trials of the drug in a
numb er of othe r indi cations, includi ng sarco idosis and
multipl e scleros is,
12
although ther e are indicati ons such as
uveitis whe re the drug remain s in earli er-stage develop ment.
As a result, our fore casts are primarily based on sales from
the RA and JIA indicati ons.
10
http://www.theph armaletter.com/file/96506 /bristol-myers-squibbs-
or enci a- get s- ex pan de d-i n di cat i on - in-e urope-a nd-reyataz- cleared-for-
pe diatric-use.html
11
The FDA approved the subcutaneous formulation in July 2011.
12
Terminated clinical trial numbers for these indications are NCT00739960
(sarcoidosis), NCT00035529 (multiple sclerosis).
9
htt p:// www.regencerx.com/docs/physicianRx/biol ogic-response-
modifiers-Humira
1
-0408.pdf
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