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Zon Zones in on Gilead’s Miracle Hepatitis C Drug (Solvaldi™)

In his latest “Zone in with Zon” blog post blog, dated March 16, 2015, and published by TriLink BioTechnologies of San Diego, Dr. Gerald Zon declares that Gilead’s new drug Solvaldi™ for treatment of hepatitis C virus (HCV) infections is “truly a drug developer’s dream come true.” And Dr. Zon should certainly know, having been intimately involved in drug discovery and development for many years. He notes that the Gilead’s nucleotide-analog prodrug is reported to produce an over 90% cure rate in HCV-infected patients over a 12-week (84-day) course of treatment that involves simply taking one pill per day. That, Dr. Zon says, is “amazing.” However, he immediately remarks that this powerful benefit comes at a considerable expense, with a single Solvaldi pill costing $1,000 and a full-treatment cost of $84,000 per patient. He adds that the estimated manufacturing cost of manufacturing per pill is $68-$138 and this huge disparity between the cost and the price being charged has been the subject of considerable controversy. Particular concerns have been raised as to how this pricing will influence the impact of this drug in developing countries where HCV infection is relatively high, and also in U.S. prison populations where HCV infection is rampant. Before addressing these and other ticklish issues, Dr. Zon provides some useful history on the development of this “miracle drug.” Apparently, it all began with work by two companies, Pharmasset, which was founded on the East Coast in 1998, and Gilead Sciences, Inc., which was founded on the West Coast in 1987. Pharmasset did significant early R&D work on development of an oral drug for HCV treatment and this work ultimately allowed the company to go public in 2007. Dr. Zon noted that the challenge was significant as HCV has different genotypes that each have to be combated, but at the same time the need was great as the only treatments then available were merely palliative at best, and the potential consequences were grave, including cirrhosis, liver failure, and liver cancer.

In 2010, Pharmasset’s continuing work resulted in a publication in the Journal of Medical Chemistry reporting that a nucleotide prodrug (a drug that is “unmasked” in vivo to generate the triphosphate form of the effective nucleotide analog moeity). This triphosphate interferes with the critical RNA replication of the HCV virus and this is how the medication exerts its beneficial effect. The Pharmasset prodrug was called PSI-797. At the same time, Gilead was also making progress pursuing a very similar objective and they too published a similarly positive report on their development of a somewhat similar drug in the Journal of Medical Chemistry in 2010. The Gilead drug was GS-6620.

Then, in 2011, in what Dr. Zon described as a move that “stunned the drug development world,” Gilead announced its intention to purchase Phamasset for a “whopping” $11 billion. This deal was finalized in January 2012. Dr. Zon thought that the extraordinary efficacy of PSI-797, despite its potential for side effects had motivated Gilead to take this huge gamble, but at the time, he also thought the purchase an example of “corporate chutzpah” by Gilead.

Now, the astounding effectiveness of Gilead’s Solvaldi seems undeniable (an over 90% cure rate!), but the debate over its cost and how this cost may limit the drug’s utility in helping humanity is raging.

Dr. Zon reports that an estimated 185 million people have been infected with HCV worldwide. Untreated, these infections can cause cirrhosis, liver failure, and liver cancer, as noted earlier. The number of HCV-associated fatalities per year is estimated to exceed 500,000 and this actually, and perhaps amazingly, exceeds the number of deaths from tuberculosis or malaria. Clearly, there is an overwhelming need for the curative treatment of Solvaldi, but how can the millions who need it ever afford it?

Dr. Zon says that Gilead has argued that its drug is not just a treatment for HCV, but actually a cure, and this, in part, makes the price tag worth it. He notes that he does appreciate the point being made by Gilead, as well as the fact that it is a for-profit company that has to factor in all of its expenses in bringing Sovaldi to market, including the $11 billion acquisition of Pharmasset, and Gilead’s undoubtedly enormous expenses for its failed in-house anti-HCV R&D.
Dr. Zon goes on to quote Gilead’s current policy on reaching out to the needy and then he provides an example of how this policy is being implemented in India.

Gilead’s policy is quoted as follows: “Gilead makes it a priority to increase access to its medicines for people who can benefit from them, regardless of where they live or their economic means. In developing countries, Gilead’s treatment access strategies include tiered pricing, voluntary generic licensing (often in advance of U.S./EU regulatory approval), negotiation with national governments, regional business partnerships, product registration, medical education, and partnerships with non-profit organizations. This approach has been successfully applied to Gilead’s humanitarian program in HIV over the past ten years, with six million patients now receiving Gilead-based HIV medicines in developing countries.”

Dr. Zon said that in September 2014, Gilead executed seven non-exclusive license agreements with seven generic drug manufacturers in India to produce sofosbuvir (the generic name for Solvandi) in 91 developing countries. These countries reportedly include over 100 million people infected with HCV.

Dr. Zon reports three “laudable” features of these licensing agreements. One is that Gilead will provide complete documentation for manufacturing to enable the Indian companies to produce sofosbuvir at scale as soon as possible; a second is that licensees set their own prices for the drug and pay Gilead only a royalty on sales to cover ongoing sofosbuvir-related expenses; and finally, that there are no restrictions on use of sofosbuvir in various combination therapies.

Dr. Zon is an eminent nucleic acid chemist and Director of Business Development at TriLink BioTechnologies in San Diego, California. The entirety of Dr. Zon’s most recent blog can be viewed at the link below. Previous Dr. Zon blogs can also be viewed at that site.

[Zon blog post]