FDA: On development of >1 Investigational Drugs for Use in Combination

[Guest guest]

For research advocates:

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/G

uidances/UCM236669.pdf

A snip from FDA guidance to the industry:

DETERMINING WHETHER CODEVELOPMENT IS AN APPROPRIATE DEVELOPMENT OPTION

Concurrent development of two or more novel drugs for use in combination

generally will provide less information about the safety and effectiveness

of the individual drugs than would be obtained if the individual drugs were

developed alone.

How much less will vary depending on a variety of factors, including the

stage of development at which the individual drug components cease to be

studied independently. For example, in codevelopment scenarios in which

rapid development of resistance to monotherapy is a major concern, it may

not be possible or appropriate to obtain clinical data for the individual

components of the combination beyond phase 1 testing.

Because codevelopment will generally provide less information about the

safety and effectiveness of the individual drugs, it will present greater

risk compared to development of an individual drug. Therefore, FDA believes

that codevelopment should ordinarily be reserved for situations that meet

the following criteria:

.. The combination is intended to treat a serious disease or condition.

..There is a compelling biological rationale for use of the combination

(e.g., the agents inhibit distinct targets in the same molecular pathway,

provide inhibition of both a primary and compensatory pathway, or inhibit

the same target at different binding sites to decrease resistance or allow

use of lower doses to minimize toxicity).

.. A preclinical model (in vivo or in vitro) or short-term clinical study on

an established biomarker suggests that the combination has substantial

activity and provides greater than additive activity or a more durable

response (e.g., delayed resistance) compared to the individual agents alone.

..There is a compelling reason for why the agents cannot be developed

individually (e.g., monotherapy for the disease of interest leads to

resistance and/or one or both of the agents would be expected to have very

limited activity when used as monotherapy).

FDA recommends that sponsors consult with FDA on the appropriateness of

codevelopment before initiation of clinical development of the combination.

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