?me-too? Drugs: Good or Bad?
proved to be considerably better than their original counterparts. Examples are a series of generations of beta-blockers, which came up after the original drug Propanalol was discovered by ICI, with most of them having merits in terms of better efficacy, cardio-selectivity and safety. Ranitidine, the first follow-up drug after the introduction of the first H-2 receptor antagonist, Cimetidine, was followed by Famotidine and in each case these “me-too” drugs had notable merits over the original drug.
Apart from the major breakthrough in the development of orally active beta lactam antibiotics of the Penicillin and Cephalosporin class, within the same oral derivatives, there have been considerable improvements brought about by change in the side chains incorporated by condensation of specific agents with 6-APA, 7-ADCA and 7-ACA. A whole new range of broad-spectrum antibiotics of these structural classes could thus be developed. In each of the major classes of antibiotics, classified according to the mechanisms of their action, namely inhibition of cell wall synthesis (Beta Lactams, Vancomycin), inhibition of bacterial protein synthesis (Erythromycin, Tetracycline, Streptomycin), inhibitors of DNA or RNA replication (Quinolones, Rifamycins), inhibition of Folate Coenzyme biosynthesis (Sulfa drugs, Trimethoprim), there have been several “me-too” drugs marketed.
An important recent example to show that ‘me-too” drugs need to be developed is the case of the oral hypoglycemic drug Troglitazone, approved as an anti-diabetic drug in 1997. The drug was withdrawn from the market following reports of unacceptable hepato-toxicity. The follow-up “me-too” drugs, Rosiglitazone and Pioglitazone are much less toxic and are today widely used. If these drugs were not developed, the withdrawal of Troglitazone would have left a major therapeutic gap in anti-diabetic therapy.
“Me-Too” drugs: Strategies for New Drug Research for Indian Companies
Breakthrough innovations in pharmaceutical industry, of new drugs, such as the first beta blocker, the first NSAID, the first of each class of Antibiotics, Calcium Channel blockers, ACE inhibitors, Sulfonyl Ureas, Biguanides, Insulin, Glitazones, Glinides, Tricyclic Anti Depressants,major and minor Traquillisers, Selective Serotonin Receptor inhibitors, H-1 and H-2 Receptor antagonists, Proton Pump inhibitors etc are relatively rare and even though a few of the original drugs under these classes are still very much in use, they have been superceded in most cases, by later generation products, many of them “me-too”. The newer drugs are discovered both through incremental innovations on the original drugs as well as through new research.
Generally the original discovery leads to feverish activity both within the innovator company as well as in Competitors’ laboratories, to develop better products in the same therapeutic category. The essential caveat for commercial success, however, is that the newly discovered molecules should meet the minimum standards of patentability. For example within three years of the discovery of the highly successful Sildinafil Citrate (Viagra), three more new versions for the same indications have been patented and developed5.
Me-too drugs also provide therapeutic advantage6. For the practicing physicians, there’s the benefit of established drug MoA with a “me-too” medication, coupled with clinical studies that – hopefully – show patient-centered benefits such as better adverse events profiles, less frequent dosing, less bothersome potential for drug/drug interactions, and so forth. A “me-too” drug is a helluva lot easier to incorporate in practice than a totally novel medication7.
“Me-Too” drugs: The hidden dynamics
The most common criticism of drug development centers on the so-called “me-too” drugs that employ the same biological mechanism as pioneer brands. This involves a lot more than such high-profile targets as the anti-ulcer drug Nexium. We should be thinking about antidepressants, cholesterol-reducing drugs, diabetes treatments, anti-psychotics, and other therapeutic categories that have seen both blockbuster sales and rapid innovation. There is quite a bit of evidence that follow-on drugs do a lot of patients a lot of good. The newer statins, for example, often out-perform the older ones in clinical trials where the endpoints are the number of heart attacks and deaths prevented.
Me-too drugs are also a powerful tool for cutting health care costs. We should be glad that our research industry does not target only brand new biological mechanisms. That would be a very expensive business model indeed. Fortunately, the industry also works on marginal improvements, exploiting opportunities to make drug therapy better and sometimes opening the door to really radical improvements that happen to lie