Novartis Example: Why Drug Discovery / Development Is Hard

FTY270 (fingolimod), an S1P1 modulator, is a T-cell specific immunosuppressant and is a hot, emerging phase III therapy for MS from Novartis (NVS). So where is the difficulty?

In the Aug. 14, 2008, issue of Nature, scientists from Emory University and the Yerkes Primate Research Center reported that, paradoxically, in a mouse model the drug also can enhance the body’s ability to get rid of chronic viral infections.

Yeah… an immunosuppressant helps mice getting rid of viruses.

The apparent biological contradiction in this paper underscores a few things (of many) that made drug development/discovery crazy hard:
1.) Most animal models of disease really really blow.
2.) Most of the time, how these compounds work at all is only a theory.
3.) Biological systems are redundant and complex. You never know what removing or adding one player will do.

Comments

[killerz:]

Since FTY720 does not actually suppress T-cell function, but rather causes them to remain inside the lymph nodes, its possible to still mount an immune response to viral antigens being presented in the lymph nodes. Activation of T-helper cells could still promote B-cell activation and the subsequent production of viral clearing antibodies.

2008 Aug 15 05:50 AM

[nova:]

One only can wonder why Big Pharma is not in any hurry to buy companies with great working pipelines like ImClone?

The second wonder is that biotech companies are valued by the Wall Street analysts without any understanding of biologics development and/or it potential.

2008 Aug 15 07:53 AM

[Eben Tessari:]

Killerz,
True, but no one predicted that a drug inducing lymphopenia would actually boost any part of the immune system before this study was done.

The conclusion makes sense now, but I think it clearly illustrates how difficult biological systems are to predict, no?

Eben

2008 Aug 15 09:46 AM

[moneysurf:]

Immunosuppressant helps mice getting rid of viruses doesn't make sense anything suppressing the immune system I have my doubts.

2008 Aug 15 04:57 PM