Wednesday, June 08, 2016

Dissecting drug price leaps: The hydroxychloroquine story

Hydroxychloroquine (HCQ) is an old drug. It’s a descendant of chloroquine, which is as old as dirt:

Chloroquine was discovered in 1934 by Hans Andersag and coworkers at the Bayer laboratories, who named it “Resochin".  It was ignored for a decade because it was considered too toxic for human use. During World War II, United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. It was introduced into clinical practice in 1947 for the prophylactic treatment of malaria.

HCQ largely replaced chloroquine in the 1940s; when it was on patent it was sold as Plaquenil. Today it’s still used for malaria, but it’s mainstay drug for Lupus (increasingly popular) and rheumatoid arthritis. Some rheumatologists use it for osteoarthritis because it’s thought to slow cartilage erosion (few studies, mixed results).

It has a fascinating 400 year history (emphases mine):

The Nine Lives of Hydroxychloroquine | RheumNow

The HCQ story begins in 1638 when the wife of the Viceroy of Peru, Countess Cinchona, acquired malaria while living in the New World. Rather than getting the “approved” therapy, blood-letting, she was treated by an Incan herbalist with the bark of a tree (eventually, named for the countess-Cinchona Tree). Her response was dramatic; when the Viceroy returned to Spain, he brought with him large supplies of the powder for general use, which at the time was controlled by the Church and was thus called “Jesuit’s Powder”.

It took nearly two centuries for the active substance, Quinine, to be isolated from the bark (and was eventually to make a name for itself as a tonic to be added to gin).

Over the next century, quinine would become a common component in folk medicines and patent remedies for the treatment of malaria in the southern states of America, as well as for generic malaise. By the 1940s, quinine, or rather its derivative chloroquine, was recognized for its anti-malarial properties and found use among troops fighting in the Pacific during WW-II. However, it was noted that this compound had significant toxicities. In 1945, a modification of this compound via hydroxylation led to the development of HCQ, which was found to be less toxic and remains in use, without change, to this day.

Over time, physicians began to experiment with the medication and, in the early 1950s, began to use it for the treatment of SLE. ….. combination therapy [for rheumatoid arthritis], which became popular in the 1980s and has culminated in the recent studies showing the notable efficacy of triple therapy when HCQ was combined with MTX and sulfasalazine.

Most of the science regarding HCQ’s mechanism of action falls in the realm of speculation…

..  has been clearly shown to reduce the number of SLE flares, reduce the severity of SLE flares when they occur, can in some cases lead to “remission” including lupus nephritis, increase the risk of flares when stopped, and decrease the doses of prednisone needed to control the disease. In at least one study, the use of HCQ increased survival in patients with SLE by 70%…

HCQ used to be quite inexpensive — in the range of $30 a month, covered by all insurances. It’s a generic drug and it’s been off patent for decades. Things changed in late 2014 and early 2015 - shortages developed and the price jumped. The 2014-2015 Ebola epidemic disrupted health care systems and led to a surge in malaria and then high demand for HCQ to treat it.

The demand surge ended, and the drug shortage resolved, but the price has stayed high. In the US a month’s supply now costs about $400. Why hasn’t the price come down?

There used to be at least two manufacturers, but now there is only one: Covis Pharmaceuticals. Covis was acquired by Concordia, a company that makes its money by increasing the costs of old drugs. Ranbaxy, an Indian manufacturer, had severe quality issues and has itself been acquired by another similar predator - Sun Pharma. Sun is another Indian multinational with substantial power in the US generic drug market. Sun has also had FDA warnings; it’s likely their competitive edge comes from dodging FDA rules.

With the price increase the most profitable payors, like Aetna, have dropped coverage for HCQ. So the price has gone up ten fold, but Aetna’s patients are paying out of pocket.  Aetna has been more profitable than less unethical competitors like Cigna. So Aetna is growing and Cigna is being acquired. That’s another reason why DOJ should block Aetna and Anthem acquisitions.

Hydroxychloroquine is just one drug, but it’s a classic story. Dodgy manufacturers, globalization and regulatory evasion, monopoly development, price manipulation, ruthless healthcare insurance companies — the same themes appear across the lengthy ASHP drug shortage page.

There are fixes. The DOJ should absolutely block consolidation of US payors. Voters should demand government function — which today means voting against the GOP. Governments should coordinate responses. We need the “public payor” option that had to be dropped from Obamacare to keep a few Dem senators on board (all GOP opposed of course). We need the national formulary price negotiations most other countries have. We need a mixture of regulatory actions, market forces and buyer coordination to drive competition into the drug manufacturing industry. We need to end the monopolies.

It all begins with voters. Fortunately we have a meaningful election coming up. If the GOP is routed they may reform as a “smart-government” rather than “no-government” party — and we’ll have a better chance at intelligent action going forward. Vote accordingly.

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