One Drug, Many Uses -- Mostly a Very Good Idea

Implications: ‘One drug, many uses’ can make lots of sense clinically and commercially.   Seeking additional FDA indications for a specific drug has obvious business benefits:  greater revenue stream, improved branding, potentially longer market exclusivity, greater franchising potential of the drug into ‘improved’ formulations/uses (ie, Astra Zeneca’s Seroquel and then Seroquel XR; or GSK’s Wellbutrin family -regular, SR, XL), and less financial/regulatory risk.   The costs of developing new drugs are massive and a looming unproven safety record well into development can be extraordinarily costly and even lethal to smaller companies.  Take for instance Pfizer’s torcetrapib which was pulled from Phase III development after safety concerns and $800M spent.  Most importantly, though,‘one drug, many uses’ can provide valuable treatment options to patients when handled properly by pharmaceutical companies and clinicians.  

Analysis: The article highlights Cymbalta – which will no doubt reward Ei Lilly heavily for its broad spectrum of uses (diabetic nerve pain, major depression, generalized anxiety) and now its newest indication, fibromyalgia, a disorder I suspect will increasingly be a target for drug development in the coming years.   There is a biological basis for ‘one drug, many uses’:  at least for central nervous system disorders, a single drug can dynamically affect a complex web of receptor targets, biologic systems, and intracellular events and produce multiple kinds of therapeutic actions.   Affecting a single serotonin-specific receptor (ie, 5-HT2a) can potentially affect mood, anxiety, sleep, appetite, and cognition, and also exert effects on other brain/neurotransmitter systems like dopamine, GABA, norepinephrine, etc…Research seems increasingly to show CNS disorders as mediated by ever more complex and dynamic processes.  One drug, then, may have wide biological potential.  

Clinically, ‘one drug, many uses’ has brought improved, better studied treatments for bipolar disorder by way of several anticonvulsants (ie, valproic acid, lamotrigine, and carbamazapine) and with others coming down the pike.   The class of ‘atypical neuroleptics,’ initially carrying FDA indications for schizophrenia, have reshaped the treatment of bipolar disorder over the past decade.  Bristol Myers Squibb made an important contribution to depression treatment by executing well-designed clinical trials for its blockbuster Abilify as an ‘adjunctive treatment’ for depression, the first such drug approval.  While a boon for BMS, the scientific and financial contributions leading to this added indication are important clinically.   AstraZeneca is seeking anxiety and depression indications for Seroquel XR, building on Seroquel’s success which itself made a mark with data (and an FDA indication) supporting its role in bipolar depression.     

There is risk, though.  Worrisome drug effects may be overlooked when the newer uses steer far from the drug’s underlying central actions or the clinician’s experience.  For instance, if Cymbalta were approved for chronic knee and back pain, it would be important for pain specialists, orthopedists, or whichever kind of clinician is prescribing to consider certain clinical and monitoring issues. Antidepressants like Cymbalta can pose serious risk to certain kinds of patients and potentially make their illness worse, such as those with bipolar disorder or who are prone to the activating effects of such drugs.   

I would take issue with the claim that one drug, many uses comes at the expense of innovation.  While seeking new uses for a particular drug will never carry the scientific cache or glamour of discovering and bringing to market a new chemical entity, considering and then executing a plan to develop other uses can be quite innovative and challenging.  Take for instance Jazz Pharmaceuticals, whose niche narcolepsy drug Xyrem is in the midst of Phase III fibromyalgia trials – a very innovative approach to this disorder.   And if one drug/many uses makes companies a bit leaner and more successful by tapping out the potential of what they already have in hand, well then there might be more in the coffers for the really innovative stuff.