A Long Strange Trip Continued

Back in November 2011, I wrote a post about the approval of a new drug for malaria by Ranbaxy Laboratories, an India-based generic drug maker and, since 2008, a division of the Japanese pharma company, Daiichi Sankyo Co. Ltd. (“A Long Strange Trip”). My point was that story of the drug, now called Synriam™, was an example of a mix of players cooperating for global health drug development: US academic medicinal chemistry researchers, a grant-supported product development organization (Medicines for Malaria Venture or MMV), a persistent big pharma willing to take a risk on a low-priced product (Ranbaxy), and a government agency willing to support a public health drug (the Indian government’s Department of Science and Technology). The trip continues, so here is an update with some clarifications of my original post.

In my first post, I missed the point that the approval granted Ranbaxy by the Indian government was conditional; an inspection of a Chinese ingredient supplier was needed. So it was not until last October that Ranbaxy announced receiving unconditional approval for India and that it was pursuing approvals in African, Asian, and South American markets with applications filed in several African countries (Ranbaxy press release). I also missed that Synriam is a “fixed dose combination” (FDC) drug being a combination of the novel, US-invented anti-malaria chemical, arterolane, and a known anti-malaria drug first developed in China in the 1950s, piperaquine. I have not found an explanation for Ranbaxy choosing to develop an FDC rather than a single active ingredient drug, but there could be several reasons, for example:

  • In its collaboration of with MMV, Ranbaxy found that arterolane alone did not provide as-good-as-expected clinical results;
  • The malaria-causing parasites are known to develop resistance to anti-malarial drugs and Ranbaxy wanted to reduce this risk by using two drugs with different mechanisms of action at the same time;
  • Ranbaxy wanted to develop a drug that was effective against both the major parasites, Plasmodium falciparum (causes 60% of cases worldwide) and Plasmodium vivax (causing 40% world wide but 50% in India), and this combination of drugs worked; and/or
  • Ranbaxy needed a stronger intellectual property position and patenting an FDC may help.

This last point did not occur to me until I read a posting at a website devoted to intellectual property issues in India (SpicyIP article). The writer, Prashant Reddy, noted that Ranbaxy’s license to arterolane is non-exclusive and therefore MMV could license competitors or may not enforce its patent rights. My guess is that Ranbaxy filed for patents on its FDC so that it had IP rights independent of those granted by the MMV license.

Since getting approval for marketing in India, Ranbaxy has been promoting the drug. The company has a website for it (Synriam) and a presentation for download (2013 Ranbaxy presentation). From these I learned that the drug has a number of attractive features:

  • Two mechanisms of action: arterolane kills parasites in the blood, providing fast relief of malarial symptoms, and piperaquine kills residual parasites, preventing disease recurrence;
  • Compliance-friendly dosing: one pill taken each of three consecutive days (compared to 6 to 24 for the drugs);
  • Kid friendly: a pediatric formulation and dose is being tested in Phase II trials;
  • Completely synthetic unlike the artemisinin-based, mainline drugs that are made from a wormwood extract;
  • Works well: 97.9% in uncomplicated falciparum malaria;
  • As fast-acting and safe as standard mainline drug, Coartum; and
  • Low price: it is sold for 130 Rs ($2.21) per 3-day course in India where there are 1.3 million cases per year.

Given these features, I imagined that the many not-for-profit, anti-malaria groups would be pleased that Ranbaxy had put in the $50 million or so to develop Synriam. But to my surprise, my review of the websites of the following found no mention of the drug and its approval:

I’m not sure why the lack of comment or interest. Is it because the drug has some fatal flaw that I am unaware of? Or it is because these organizations are invested in fighting malaria their way and Synriam doesn’t fit? I found an editorial published this week in the New Telegraph of Nigeria (“Towards Curbing the Malaria Menace”) that gives the perspective of a writer in a malaria endemic country and excerpted the following:

  • -Nearly all Nigerians (97 per cent) are at risk of at least one malaria attack per year.”
  • “… a princely N480 billion [about US$3 billion] is expended annually on antimalaria campaigns even when the impact is not altogether appreciable in the fight against the scourge.”
  • “Compared to other diseases, malaria is one of the most marketable diseases that shares a large funding pool by international donor agencies.”
  • “Thus for it to still remain a major killer disease in the country 14 years after a concerted campaign was launched in 2000 by African leaders, is an indication that perhaps, the various strategies adopted to eradicate the scourge are inadequate.”
  • “We strongly recommend that governments and corporate bodies take keen interest in research and adequately fund relevant institutions in the country to embark on manufacturing effective anti-malarial drugs.”

According to my math, Nigeria could treat its 100 million annual cases with Synriam at a cost of $212 million, and I think Ranbaxy would not be adverse to manufacturing Synriam in Nigeria. What am I missing?

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