Hepatitis C Drugs Cost a Fortune, But Is Worth It (Alternative: No Treatment)

choi

Paul M Barrett and Robert Langreth, How Much Should a Miracle Cost?  Thanks to two blockbuster drugs, millions of hepatitis C sufferers now have access to a cure, but insurance companies and lawmakers are balking at the price tag--$1,000 a pill and up. The story of a biotech breakthrough that ignited the latest US health-care battle. Bloomberg BusinessWeek, June 8, 2015.
www.bloomberg.com/news/articles/ ... cures-spur-backlash

Quote:

"Over the past 18 months, the emergence of Harvoni and its predecessor, Sovaldi, has given tens of millions of hepatitis C patients around the world hope that they can be permanently rid of a debilitating illness. Not since the introduction of HIV/AIDS drug cocktails almost two decades ago has the appearance of a therapy spurred such demand. Unlike drugs for HIV, which control infection and must be taken for the rest of a patient’s life, Harvoni and Sovaldi [both from Gilead] typically eliminate the virus they target and do so quickly. (Sovaldi is taken with interferon or a third drug; Harvoni combines Sovaldi with another Gilead compound into one pill and eliminates the need for interferon.)  The promise of a cure, however, doesn’t come cheap. * * * the drug [Sovaldi] would cost $84,000 for a 12-week course, or exactly $1,000 a pill. * * * Gilead’s market capitalization has soared from $29 billion to $167 billion in five years. The net worth of its chief executive officer, John Martin, exceeds $1 billion.

"The son of husband-and-wife chemists, [now 64] Martin received his doctorate in organic chemistry from the University of Chicago * * * Gilead was founded in 1987 by Michael Riordan, a physician with a Harvard MBA. He named the company for the 'balm of Gilead,' an ancient healing resin mentioned in the Bible. Riordan sought to commercialize so-called antisense treatments for genetic disorders, but his plans fizzled in the lab. In 1996, Riordan was replaced as CEO by Martin, who’d joined Gilead from Bristol-Myers Squibb hoping to pursue antiviral therapies based on his research on nucleotides, organic molecules that serve as building blocks of DNA and RNA. The company’s chairman was Donald Rumsfeld, who stepped down in 2001 to become President George W Bush’s secretary of defense. Martin later took on the chairman’s title as well.

"Gilead joined several companies that were shifting resources to hepatitis C. In addition to the 3 million victims in the US, some 150 million people worldwide are thought to have the disease. * * * Rather than simply double down on their own R&D, Gilead management ordered its researchers to synthesize and test every competing compound, with an eye toward acquiring the best. For hepatitis C, a clear winner emerged: PSI-7977 [which in 2013 was christened with the brand name Sovaldi], an experimental pill developed by Pharmasset, a Princeton (NJ) startup with 82 employees, no product on the market, and a $91 million loss for its prior fiscal year. [In November 2011, Gilead acquired Pharmasset for $11 billion.]

"More and more pharmaceutical manufacturers are seeking to develop specialty drugs because of the rich payouts associated with Sovaldi and Harvoni. Profits can be so hefty because the American health-care finance system allows companies to charge more or less what they choose. In Europe, governments negotiate directly with manufacturers, which keeps prices lower. In the US, that doesn’t happen. Medicare, the federal insurance program for senior citizens, is barred by law from using its size to negotiate discounts.

"Half of the 38 cancer drugs introduced since 2010 cost $10,000 a month or more. All were at least $5,000 a month, according to data from Memorial Sloan Kettering Cancer Center in New York. Some of those drugs merely extend life expectancy for a matter of months


My comment:
(a) While this article is interesting, there is no need to read the rest.
(b) Gilead
en.wikipedia.org/wiki/Gilead
(The Hebrew Bible repeatedly mentions a "balm in Gilead" or "balm of Gilead," references and symbolism which have appeared repeatedly in Western culture)
(c) hepatitis C virus
en.wikipedia.org/wiki/Hepatitis_C_virus
(has a proteinaceous coat and a positive sense single-stranded RNA genome. The genome consists of a single open reading frame [meaning: a coding region for a single protein] that is 9600 nucleotide bases long, which is translated to produce a single protein product of around 3011 amino acids. The single protein is then further processed to produce smaller active proteins: 3 structural (they are E1, E2 and p7 (E = envelope); to make up the coat) and 7 nonstructural (NS) proteins. The latter includes RNA-dependent RNA polymerase NS5B (some others are NS2, NS3, NS4A, NS4B and NS5A). The virus replicates mainly in liver cells, but also in monocytes of peripheral blood (accounting for immunodeficiency). From the positive-sense viral genome, NS5B, which produces a negative strand RNA intermediate; the negative strand RNA then serves as a template for the production of new positive strand viral genome.  Hepatitis C virus is predominantly a blood-borne virus, with very low risk of sexual or vertical transmission.  Unlike hepatitis A and B, there is currently no vaccine to prevent hepatitis C infection)
(d) The drug, whose brand name is Sovaldi, has sofosbuvi as United States Adopted Name (USAN; a name given by a committee when FDA approved it). Sofosbuvi
en.wikipedia.org/wiki/Sofosbuvir
is a nucleotide analog.

section 4 Mechanism of action: In the graphic, metabolism of sofosbuvi in human liver cells starts from the bottom UP to the center and then to the right, which is the final active product. The nucleotide to the LEFT of the center was the old, failed approach (by other companies). The final active product, looks similar to uridine triphosphate, fool viral NS5B -- but NOT human polymerases (for DNA and RNA alike). Compare the structure of final active product (in section 4) with that of uridine triphosphate
en.wikipedia.org/wiki/Uridine_triphosphate
, one can tell the differences are two (both in the ribose, the five-member ring in the middle): sofosbuvi has CH3 (instead H) and F (in lieu of OH) on the same carbon atom (not marked).