About a month ago, the US FDA announced that it had granted a Canadian company, Paladin Therapeutics, approval to sell a drug called Impavido® to treat leishmaniasis, a nasty, protozoan infection that occurs annually in about 1.3 million, mostly poor, people and causes 20-30,000 deaths (WHO Fact Sheet). The press release in FierceBiotech also stated that Paladin received a Tropical Disease Priority Review Voucher (PRV), only the third one granted. The PRV process is intended to encourage development of drugs for neglected diseases, and the FDA will expedite review of a drug submitted by the holder of a PRV, and the company has sales sooner as a result. And since it is transferable, the holder can also sell it, although none have been sold (or used) to date. I found it interesting that the FDA would make the announcement and not the company and was more perplexed when I found that Paladin was no longer in business, having been purchased in 2013. But before untangling that web, I looked up background on Impavido.
Impavido is the name trade-marked by the Æterna Zentaris Inc., a German company, for a drug with the generic name of miltefosine. Miltefosine was designed and developed in the 1980s as an anti-cancer drug, was found to be a broad spectrum antimicrobial, and developed as the first (and only) oral treatment for chronic leishmaniasis by ASTA Medica (later Zentaris GmbH), the WHO Special Tropical Diseases Programme, and the government of India in the 1990s. Subsequently, Zentaris got approvals for Impavido in Germany, India, and Central and South America (the last through licensees), and miltefosine is made by at least one Indian generics company for the domestic market (nicely summarized by Dr. Anthony Crasto in his blog, New Drug Approvals, and at docguide.com). So why isn’t Impavido/miltefosine being widely used to treat leishmaniasis (which has three forms- visceral, also known as kala-azar and the most serious form; cutaneous, the most common; and mucocutaneous)? I looked at the Drugs for Neglected Diseases Institute’s (DNDi) website since this grant-supported, not-for-profit has a major program to develop visceral and cutaneous leishmaniasis drugs (DNDi Strategy), but could not find a clear reason. My read is that DNDi believes that the drug’s course of treatment (28 days) and immediate improvement may result in poor patient adherence and development of resistance, the drug’s potential fetal toxicity makes it unsafe for reproductive-age women, and its cost is too high for monotherapy (about $80 per course at the current WHO-negotiated preferential price). Dorlo et al. had a more positive assessment in their 2012 review, concluding that, as a well-tolerated and oral drug, miltefosine should be a viable option for many patients.
What about Impavido’s use as a treatment? All rights to the drug were bought by Paladin, a successful, Montreal-based specialty pharma retailer founded by Jonathan Goodman, from Zentaris in 2009 (PRNewswire release). Paladin apparently continued Zentaris’s commitments to its licensees and WHO purchasers, selling about $2.5 million worth out of total annual sales of $200 million. In November, 2013, Endo Health Solutions, Inc., a US-based specialty pharma company, bought Paladin for about $2 billion in cash and stock (Reuters article), in part to extend its product line and in part to reduce its US corporate tax liability. Since the acquisition was done through an Irish holding company, some analysts call the deal an end-run around the IRS (e.g., Zerohedge.com blog), interesting but not relevant. What is relevant is that Mr. Goodman negotiated retaining Impavido ownership as one of the assets for his new company, Knight Therapeutics, which he founded just after the Paladin sale. Knight is off to a good start with $60 million invested by Mr. Goodman, another $180 million from other investors (Cantech Letter), and an IPO on the Toronto Stock Exchange in March (Waterhouse article). Why did Mr. Goodman keep Impavido as the company’s first product? It’s not clear to me. According the two above-cited sources, Knight licensed Impavido’s non-US rights to Endo so will get about $500K in annual royalties (peanuts for a company with a market capitalization of about $140 million), and Knight has the drug’s PRV (value to be determined). According to the company website (Knight Products), it is developing a commercialization plan for the drug for the US market, although leishmaniasis is very rare so revenues are likely to be small.
Mr. Goodman is clearly an experienced and successful entrepreneur, building Paladin from a start-up to a public company, and is wealthy from the Endo deal (he owned one-third of Paladin’s stock as reported in a Globe and Mail article). He also has a different perspective on life after an almost fatal bicycle accident in 2011 that I, as a road biker and commuter, can relate to. Two weeks ago, Mr. Goodman posted a note called To Define Success in which he wrote “Success is defined by the good we do for others.” He ended with:
The more you practice the cycle of giving, the easier and more rewarding it becomes – it is now my new addiction (I gave my bicycle to my cousin). Anyone can repair our world. Anyone can make a difference. Any currency can be used, whether it is money, knowledge or your time. Knight’s stock ticker is GUD, not derived from Goodman, but for the hope we all do good.
My humble suggestion is that Mr. Goodman use his money, knowledge, and time to get Impavido used to treat as many of the 12 million people with leishmaniasis as possible.