New drug development is a series of complex activities invariably involving tremendous financial investment. The undertaking, to bring a new drug to market, makes it almost impossible for smaller, privately held pharmaceutical companies, to even dream of such endeavors.
Is it possible for companies, lacking the resources of the pharmaceutical majors, to expand the use of existing drugs, established in some countries but not marketed in others?
Our PharmaCompass analysis this week looks at products, which have monographs in the European Pharmacopoeia but have never been approved in the United States.
Would it surprise you that amylmetacresol, one of the two active ingredients in Strepsils, one of the world’s largest-selling sore throat product has never been approved for use in the United States?
-Reckitt Benckiser, the company that owns the Strepsils brand, markets Cepacol for sore-throat relief in the United States. While Strepsils contains, amylmetacresol and dichlorobenzyl alcohol, Cepacol has a completely different set of active ingredients i.e. benzocaine and menthol.
-Interestingly, while on the topic of throat relief, pholcodine, an opioid cough suppressant, is not prescribed in the United States where it is a Schedule I drug. However, as a class B substance in the United Kingdom, it can be purchased over-the-counter (OTC) in most pharmacies.-Hypertension and congestive heart failure drug cilazapril is sold across Canada and other European countries. Although cilazapril is supposed to have limited advantages over other drugs in the same class, exports out of India to Turkey, New Zealand and Canada indicate a robust demand in these countries.
-Some molecules, discovered in France like, anti-diarrhoeal drugs nifuroxazide and racecadotril, lipid lowering ciprofibrate or anti-cancer agent buserelin are used extensively in select countries. However, for reasons unknown, they have never been approved in other parts of the world.
-Lymecycline, a broad-spectrum antibiotic belonging to the tetracycline class, is used in the treatment of acne and marketed by Galderma SA, a completely owned subsidiary of Nestle. Lymecycline is 5,000 times more soluble than tetracycline base and has unique pharmacological activity amongst the tetracycline class of molecules. As the product has been on the market for over a decade, generic versions are now also available across Europe.
-As antibiotics continue to get increased attention in view of the growing concern of ‘superbugs’, there are antibiotics like roxithromycin and flucloxacillin, which are sold in the UK and Australia but have never obtained approval in the United States.
Are these products safe?
Countries like France, United Kingdom, and Canada, where many of the above mentioned drugs are marketed, have active pharmacovigilance programs, which monitor drugs, should there be any serious adverse events. Continued use for years in well regulated pharmaceutical markets is usually proof that the products are safe.
However, for the antibiotic flucloxacillin, concerns have been identified regarding a genetic link associated with liver injury. While flucloxacillin has not been approved in the United States, the FDA website does provide details on this risk.
Liver toxicity concerns have limited the sales of some commonly used OTC products like nimesulide and propyphenazone (brand name: Saridon) in some countries. Yet, there are parts of the developing world, where the sales continue to increase.
There are graver concerns for products like cisapride, which was launched by Janssen for increased motility of the gastrointestinal tract but was withdrawn, from the US market, due to concerns of fatalities linked to cardiac arrhythmias. The product continues to be exported from India to countries like Switzerland, Thailand, Mexico, China and Canada.
Reviewing the export data out of India, on the PharmaCompass database, it is clear that in the markets, where the above mentioned products are sold, there is substantial demand.
Major pharmaceutical companies have little incentive in taking old molecules global since there is little intellectual property protection to assure the profits that they are used to. However, for others there may be an opportunity worth considering.
Launching a new product is always a Herculean challenge, but hopefully the successful use in existing patient populations, is a good starting point.
API manufactures can also review these products since there may be better margins in these niche molecules when compared with others, which have become commodities.