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KP157: A
Drug to Treat Depression
Development stage:
KP157 (also known as CX157) has been licensed to CeNeRx BioPharma under the brand name Tyrima. Phase II clinical trials in progress.
Indication:
Depression, anxiety.
Overview:
KP157 is a new drug for the treatment of depression and anxiety which effectively and reversibly inhibits Monoamine Oxidase A (MAO-A) with no effect on MAO-B. The drug does not induce acute hypertension in the presence of high dietary tyramine (the "wine and cheese effect") that was a major problem with earlier non-reversible MAO inhibitors. In addition, KP157 is the only selective inhibitor of MAO-A that is not an enzyme inducer. These properties should translate to the first truly safe representative of this class of inhibitors, for which efficacy is well established.
KP157 is a fluorinated phenoxathiin. A chemically related compound (BW1370U) taken through Phase I clinical studies by a major multinational (the original owners of the technology) showed no indication of sedation, stimulation or agitation, and no adverse anticholinergic, gastrointestinal or cardiovascular side effects. This earlier compound, however, did cause some liver enzyme elevation in a few test subjects at very high dose levels. This problem led to the development of KP157, a close structural analog which is more potent than the earlier compound, has improved pharmacokinetics, and has tested negative for liver enzyme elevation.
Market Opportunity:
The antidepressant market is dominated by selective serotonin reuptake inhibitors
(SSRIs) After extensive clinical experience, it is now known that about one-third
of the depressed population does not respond to SSRIs. Another third respond
only partially. Moreover, these drugs have a slow onset of action which is
a serious problem when treating clinically depressed and potentially suicidal
patients, and negative side effects such as insomnia and sexual dysfunction
are common.
KP157 has a totally different mechanism of action and early indications are
that it will have a more rapid onset of action and a better safety profile
than the SSRIs.
The in vitro and in vivo properties of KP157 suggest that this compound and
its close analogues are among the most potent MAO-A inhibitors known. In view
of the very positive results obtained thus far with KP157, and on the basis
of extensive prior experience with this class of drugs, KP157 has excellent
commercial potential as a selective, reversible MAO-A inhibitor for use in
the treatment of depression, anxiety and other brain disorders. |
