dRug discoveRy & develoPment 11
A new approach to early drug
discovery promises faster results
he route a new drug takes to market forward into man, following regulatory approvals.
Andrew Rankin explains
is long and costly. Time and money But as costs rise and timelines are compressed,
how getting a drug
saved along the way by improving this two-stage iterative approach is becoming less
candidate into the clinic
T
processes is valuable. Bearing in viable. In addition, data suggests that the initial
early can pay dividends. mind that the cost, both in terms of time and lost animal models are often a poor predictor of a
market opportunity, when a drug fails in drug’s performance in man (Fig. 1).
late-stage development is so significant, it is very New approaches are now emerging to help.
Andrew Rankin nous
important to be able to predict problems early Specialist early development companies with
explique comment le
passage précoce d’un
in development and either ‘develop issues out’ integrated GMP/GCP facilities offer rapid and
médicament candidat
or move on to more promising candidates. In flexible make-test protocols, and can manufacture
au stade clinique peut
this environment, companies are well advised to a new formulation and test it in-clinic within
s’avérer payant.
invest more time and analysis in earlier stages 24 hours. This can reduce the time to develop
of clinical development in order to reduce costly a new dosage form by as much as 50 per cent,
late-stage failures. and significantly reduce costs. Fig. 2 presents
Andrew Rankin
So what are some of the issues facing drug a comparison of the traditional approach and
erklärt, wie es sich
developers today? an alternative model in which formulations are
auszahlen kann, einen
Oral drug administration and simplified administered to volunteers in the clinic within
Arzneimittelkandidaten
frühzeitig in die klinische
dosing, ideally once-a-day, is the holy grail for 24 hours of manufacture.
Phase zu bringen.
many companies. Research has consistently Where issues of bioavailability arise in these
shown that once-a-day administration positively initial clinical studies, a new human data-driven
impacts on patient acceptability, and improves approach can help to move development forward
compliance and commercial success. But it does (Fig. 3). The combination of Enterion regional
present significant development hurdles. Many absorption studies that provide a detailed picture
candidate compounds exhibit less than ideal of drug absorption, and intravenous microdosing
pharmacokinetics and a modified release (MR) studies that probe questions of absolute
dose form is often required. The number and bioavailability, metabolism and drug-drug
complexity of variables driving the choice to interactions, provide a reliable basis for decision
develop a MR formulation, and the number of making concerning a candidate drug.
options available once that decision has been This is a combination of new thinking and new
made, make this a very challenging process. technology. The technology is important (see box),
Developers have long relied on making but the power of the approach is realised through
and testing different formulations, comparing know-how and interpretation. We work hard to
the results and then modifying and retesting. turn the early clinical data on a compound into
Following in vitro characterisation, formulation valuable knowledge that informs the later stages
prototypes are traditionally tested in animal of development.
models first, with a smaller number then going So what difference can this approach make?
➠
Fig. 1. Animal
models are
not ideal for
predicting
a drug’s
performance
in man.
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