Biomedical Engineering Reference
In-Depth Information
structure s, potential ly allow inhaled , topical, and even oral
alternat ives to be developed. Similar ly, needle- free inject ion
devices may also reduc e the inconvenience of treat ing
disorders that have traditi onally been the realm o f injectable
biologics. These innovations, theref ore, threaten to disrupt
the market for a number of long half-life FPs, although the
burden of a mor e frequent inj ection regimen shoul d perhaps
not be overstated. Traditiona l needl e and syringes are
depend able, low cost, and relat ively painless. Th is became
all too appar ent to Pfizer with its inha lable insuli n produc t,
Exuber a
1
. It was taken off the market in Octobe r 2007 after
the high price, cumbers ome device and dosin g conce rns
resulted in only minimal levels o f sal es. Sim ilarly, Eli
Lilly/A lkermes and Novo Nordis k/Aradigm als o terminated
development of compet ing projects. MannK ind has though
continue d with Afrez za
1
, which may in part relat e to the
company having few alter native pipeline options com pared
to larger rivals. Th e product has struggled with regulators,
receiving two Compl ete Respons e Letter s from the FDA.
MannKi nd is due to commen ce further clinical studies with a
new thumb- sized device that may overcome som e of the
comme rcial issues that prevented the 200-mL sized Exubera
from achi eving success.
Further technologies in development are designed to
reduce the frequency of injections by having drug-producing
factories set up in the body. Gene therapy approaches use
viral or other vectors to insert DNA into a patient's cells,
resulting in expression of the desired therapeutic protein.
Sanofi/Oxford Biomedica's Retinostat
1
is a gene therapy in
Phase I for age-related macular degeneration (AMD). It is
administered via a one-off injection. Long-term follow-up
studies have shown gene therapy to be effective for over
10 years without repeat doses [38]. If successful, the
product could potentially impact the commercial outlook
for AMD treatments such as Roche's Lucentis
1
, or Regen-
eron/Bayer's FP, VEGF Trap-Eye, which are required once-
monthly in the first year then approximately every 4-12
weeks (see Chapter 2). Similarly, cell therapies involve the
administration of whole cells that have been engineered to
produce a therapeutic agent and potentially also offer
infrequent administration. With Medgenics' Biopump tech-
nology, cells are first collected from the patient, which then
undergo gene therapy before being re-implanted. The com-
pany has reported that a single implantation of erythropoietin
(EPO) Biopumps was sufficient to provide sustained treat-
ment of anemia for more than 2 years.
10
These gene and cell
therapy approaches can also be used for the expression of
FPs to either reduce dosing frequency further, or facilitate
novel mechanisms of action. Heat Biologics' HS-110 is a
Phase I/II candidate that involves the injection of engineered
cells that secrete a gp96-IGg FP for the treatment of cancer—
gp96 is a chaperone that binds to tumor antigens and delivers
them to APCs. Similarly, Advaxis' ADXS11-001 is a vaccine
based on attenuated Listeria that is engineered to produce a
truncated virulence factor fused to a tumor-specific antigen,
which then generates an anticancer immune response. As
stated at the start of this chapter, we have excluded HS-110
and ADXS11-001 from our total of 43 FP products since they
are not administered as FPs, but instead are expressed in the
body. It is notable that lower administration frequency does
not always mean a better profile, and continuous therapeutic
exposure can also result in side effects being exacerbated.
This was raised as a concern by the FDA regarding Eli
Lilly's once-weekly exanatide formulation, Bydureon.
11
Furthermore, many long-acting formulations cannot be
removed quickly from the body in the event of adverse
reactions occurring.
In this discussion of the factors of comme rcial succe ss,
we flag the imp ortance of focus ing on produc ts that offer a
suffic iently stron g profile agai nst the evolving marketpl ace.
The key patents for several mature ther apeutic protein
classes , such as erythro poetins, blood factor s, IFN s, and
insulin s, have either expired, or are soon to. As such, there
can be grea ter scope for FP and non-FP platform play ers to
develop next-generation version s of these molecu les than for
say more recently launched produc ts where there may be
less freedom to operate . The downs ide of this is though that
witho ut broad under lying IP, these opportuni ties will also be
availabl e to comp etitors and it is of no surpr ise to fin d a
consider able number of next-generation products in thes e
expiring protein classes . Although proven mechani sms of
action do represe nt a lower risk strategy for validati ng a new
platfo rm, promising in-licens ed or newly discovered targets
should also be consider ed for in-house development project s
once the extended half-lif e or improved administ ration
technol ogy has been validated. As with many aspec ts dis-
cussed in this chapt er, the factor s of com mercial succe ss
should be considered o n a case-by-cas e basis. Fu rthermor e,
while we consider it import ant to prope rly asse ss the advan-
tages and disad vantages of compet ing administ ration
appro aches, this shoul d be in the cont ext of wider factor s
includi ng effica cy, safe ty, and cost.
3.2.2 Effi cacy Profile
A primary factor linked to the commercial success of any FP
product is the level of efficacy it can achieve compared to
alternatives. Patients are given medicinal agents to treat or
prevent a particular disorder. Treatments offering greater
efficacy stand out when it comes to making a prescription
choice. The stringency of efficacy requirements depends on the
risk-reward ratio offered by a product in the indication sought.
10
http://marketbrief.com/mdgn/8k/events-or-changes-between-quar/2011/
5/3/7870770/filing
11
http://phx.corporate-ir.net/phoenix.zhtml?c
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