We expected the publication of the article on the synergy of therapeutic indication and choice of presentation or choice of active ingredient to elicit quite a lot of interest, but in the event, the enquiries we have received surpassed our expectations. Visitors to our website will already have seen some of the strategy aspects, without the example products to which the strategy applies.
The opportunities for utilising this technology to develop low risk, highly differentiated innovative products are clearly apparent. The low risk element derives from the knowledge of the efficacy of a certain compound (or class of compound) in a certain secondary indication, that is often discovered but imperfectly commercialised some time after the launch of a product for its primary indication.
Often large pharma companies decry the therapeutic switch strategy as ‘not their game’, yet the APT strategy clearly is. This was brought home to me recently at the Society for Medicines Research meeting on Recent Disclosures of Clinical Candidates, in a talk from Pfizer on long-acting PDE5 inhibitors.
Pfizer were in many ways ahead of the pack in using therapeutic indication as a variable in the definition of Viagra’s utility, and established erectile dysfunction as a legitimate area for pharmaceutical treatment. Some time later, they brought the first PDE5 inhibitor to the market for pulmonary arterial hypertension (PAH), another emerging indication of inquiry [and the source of enormous commercial success, despite its rarity, for Actelion’s dual endothelin receptor antagonist bosentan…but that’s another story].
The Pfizer story behind their two products for erectile dysfunction and PAH is interesting because Viagra and Revatio both contain the same active ingredient (API), sildenafil, but under different brands, doses and at different prices. Of course, the two markets are quite differrent in many other ways too. Whereas erectile dysfunction struggled early on to be recognised as a real disease worthy of therapeutic intervention, no-one could say the same about PAH, for which in the idiopathic form, the duration from onset of symptoms to death is an average of 2.8 years. This differential seriousness normally underpins very different pricing regimes, but in this case, the common API undercuts that argument. And then, there is also the aspect of chronicity.
While ED is not a condition that necessarily requires chronic intervention (joking aside), PAH clearly does. And interestingly, Lilly’s tadalafil (Cialis), which is marketed in its primary indication on the basis of utility for a whole weekend of romantic endeavour, has no need of imaginative straplines in its secondary utility for PAH, for which it was approved earlier this year.
Again with a different dose and a different trade name (Adcirca), the real strength of tadalafil for PAH is its longevity of action. This placed Pfizer for the first time at a slight disadvantage, despite having the first products in the area as a whole, and for PAH in particular. At this point, they established a discovery programme for a long acting PDE5 inhibitor to more compete more effectively with the new entrant.
For me, the interesting point was the extent of the discovery programme. As described by their Medicinal Chemistry programme leader, David Fox, the discovery went back to first principles, with a completely new substructure emanating from a long and winding hit-finding, then lead optimisation programme.
One ostensible reason was the insufficient half life in the sildenafil template (or analogues thereof); but another, and I suspect the major reason, was the highly differentiated patents that came from the approach they followed. Strong patents are a necessary but not sufficient reason for all R&D. A reformulation may actually have produced the same endpoint, and in the event a lack of clinical differentiation will in any case make the new structural scaffold a moot point.
For me the essential message is that taking a secondary indication and a slightly modified formulation or active ingredient can represent a highly attractive route to new product discovery…and one that small biotech and large pharma can both agree on. But one needs to remember that in the market, differentiation drives value.