Principles and Practice of Pharmaceutical Medicine

new drug is preferable for a company. However,
there are some exceptions to this rule, depending
on the degree of patent coverage and the number
of years left at the time of initial marketing.
There are also various states of a patent to con-
sider. For example, patent status may be char-
acterized as nonpatentable, applied for, in
interference, under final rejection, approved but
not issued, approved and issued or another sce-
nario may apply.
Drugs are either investigational or marketed,and
orphan drugs are no different. They may be used to
treat only rare diseases, or both rare and common
diseases. They are deemed orphan only for the rare
disease indication.
The clinical value of drugs being developed for
rare diseases varies along the same spectra that
existfor all drugs. Thisrunsfrom having noclinical
efficacy or medical value (for any of many reasons)
to extremely high medical value that will revolu-
tionize medical practice.
Development costs, time to market and commer-
cial potentialvary enormouslyamong orphan drugs,
as with all drugs. It is usually meaningless to
develop an orphan drug if a generic is available on
the market or will be shortly (i.e. before the com-
pany can launch its product). Even if the generic
version isnot officially indicated for treating the rare
disease, it is likely that the generic version will be
used for the treatment of the rare disease.

21.3 Classification of orphan

drugs

Although classification of orphan drugs may be

made along several lines, no single classification

has been accepted as universally acceptable. In

fact, several classifications have been proposed

(Spilker, 1991). This section briefly mentions the

criteria on which a classification scheme could be

based and describes a simple classification based

on economic value combined with medical value.

The major criteria that may be used to create

a classification of orphan drugs include the

following:

1. Therapeutic or disease area of the drug.


2. Marketed status of the drug (i.e. marketed or
   investigational).


3. Patent status of the drug (e.g. patent issued and
   in force, patent expired, nonpatentable, patent
   pending).


4. Generic drug availability (yes or no). Availabil-
   ity in the same dosage form, strength, with
   same excipients, and any other factors that are
   relevant to consider.


5. Size of patient population. This refers not only to
   those in the parent country, but in other countries
   as well. Considerations of closely related subsets
   of patients must be considered because it is not
   possible to obtain orphan drug designation in the
   United States if the drug can be used by a closely
   related subgroup of patients [e.g. one type of
   epileptics vs. another; or a large number of mod-
   erately ill who can readily benefit from a drug as
   well as a small number (under 200 000) of
   severely ill patients with a particular disease].


6. Can drug development costs be recovered
   through sales? Although this criterion was
   very important in the original Orphan Drug
   Act of 1983, it was eliminated a short time later.
   This could be considered important for both
   legislatorsaswellaspharmaceuticalcompanies
   that are considering developing orphan drugs.

Table 21.1 Reasons why orphan drugs are a
heterogeneous group

Orphan drugs differ according to:

1. medical value


2. patent status


3. investigational or marketed status


4. availability in a generic equivalent form


5. use for a common disease too


6. costs of development


7. commercial (and profitability) potential


8. disease prevalence (stable, increasing or
   decreasing)


9. availability of alternate therapies


10. manufacture by conventional or biotechno-
    logy methods

266 CH21 ORPHAN DRUGS