MedicalResearch.com Interview Questions
Carlos del Rio, MD
Chair, HIV Medicine Association
Department of Medicine
Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases
Emory University School of Medicine
MedicalResearch.com Editor’s note: Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis.
Medical Research: What is the background for this Express Scripts announcement?
Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc. ID and HIV clinicians told us they had been having difficulties obtaining pyrimethamine since earlier in the summer when Impax implemented a controlled distribution system making the drug available only through Walgreen’s Specialty Pharmacy.
Despite HIVMA, IDSA and others urging Turing to reverse the price hike, no action was taken and providers continued to report the scarcity of the drug due to the cost and issues with the distribution system.  Due to these ongoing challenges, HIVMA and IDSA thought it was important to provide information to our members and other providers regarding the new lower cost option so they could evaluate this option in consultation with their patients. Initially Turing agreed to reconsider the price increase and to lower it; however, on Nov. 24th Turing announced that they would not lower the list price of Daraprim but instead planned to offer discounts of up to 50% to some hospitals.  The announcement reinforced the urgent need for affordable treatment options and failed to address that a majority of the eight to twelve month treatment course occurs on an outpatient basis.
Medical Research: What has lead to the dramatic increase in the price of pyrimethamine?
Dr. del Rio: As mentioned, the increase from $13.50 per tablet to $750 per tablet occurred immediately following Turing Pharmaceuticals’ purchase of the medication from Impax in August 2015. Just over five years ago, pyrimethamine was available for $1 per tablet in the U.S. from the original manufacturer GlaxoSmithKline. The drug continues to be available at that rate or lower in countries outside the U.S.
Turing insists that pyrimethamine is adequately and fairly priced at its current level, and in fact should have been priced higher, to allow its investors to maximize profit and to generate funding for the development of new treatments for toxoplasmosis. While we support investments in toxoplasmosis research, it is unacceptable to fund new drug development by overcharging for existing treatment– thereby restricting access to patients in need now.
Medical Research: What real or potential impact does this price increase have on patient care?
Dr. del Rio: Ready access to treatment of toxoplasmosis is important as severe toxoplasmosis can result in brain and organ damage, blindness and death. The price increase and controlled distribution system continue to present barriers to treatment and place significant strains on providers and hospital systems. IDSA and HIVMA members have reported that patients have experienced treatment delays and extended hospitals stays and that significant provider resources have been devoted to securing a medication that before this summer was easily accessible. In light of access issues, the Department of Health and Human Services modified its guidelines for the Prevention and Treatment of Opportunistic Infection in HIV-infected Adults and Adolescents in October 2015 to include treatment alternatives when Daraprim® is not available.
At my own institution, Emory, we were unable to purchase the drug for several months over the summer due to the new distribution system. For FY 2015, we purchased 14 bottles of Daraprim for $18,000. In FY 2016, this same volume will cost our health system $1.05 million at the drug’s list price or $525,000 if we secure the maximum discount of 50% that Turing indicated would be offered to some hospitals. At these prices, hospitals are forced to make difficult financial decisions and trade-offs in determining whether they can afford to stock a bottle.
No discounts are being considered for health insurers and these costs will be born by patients, taxpayers and the health care system. We have reports of patients with insurance being quoted cost sharing levels as high as $27,000 per month and expect to see more restrictions imposed by health insurers on pyrimethamine.
Medical Research: How will the Express Scripts plan mitigate these effects?
Dr. del Rio: Express Scripts’ coverage of the Imprimis alternative offers a lower cost option for medical providers to consider and discuss with their patients. The option also is available to patients without Express Scripts coverage, but they will be responsible for the full cost of the treatment. Additional information is available from our website.
Medical Research: Are there any other points you would like to make?
Dr. del Rio: The sudden and dramatic price increase taken for pyrimethamine has shined a spotlight on the vulnerabilities of market-based drug pricing particularly for diseases and conditions without competition and where there is little incentive for competitors to enter the market, such as treatment for toxoplasmosis. Interventions are needed to prevent companies from unfairly leveraging the value of an off-patent medication with little or no competition. Interventions also are needed to prevent companies from using controlled distribution systems to create a monopoly for off-patent medications.
Pyrimethamine provides an extreme example of high drug prices for older medications impeding patient care. Sadly this is not an isolated case and appears to be part of a growing trend. The infectious diseases community has recently experienced other price hikes forcing providers to deviate from preferred treatment regimens. An example is flucytosine, a key component of the preferred treatment for Cryptococcal meningitis. The price of flucytosine jumped from $10 a tablet to $110 tablet after the drug was purchased by Valent Pharmaceuticals.
And there’s more to come. Earlier this month KaloBios, recently acquired by Martin Shkreli, purchased a version of benznidazole – one of two drugs used to treat Chagas Disease. Chagas disease is a parasitic infection most common in Central and Latin America. The Centers for Diseases Control and Prevention estimates there are 300,000 individuals with Chagas in the U.S. A majority of them immigrated to the U.S. and many of them are poor. Currently no drugs are approved for treatment of Chagas in the U.S. but the CDC offers free access to benzinadazole and niturtimox through a compassionate use program. The reported plan for Mr. Shkreli to charge $60,000 to $100,000 for a treatment course will leave treatment for this potentially lethal condition out of reach for those who need it. While Chagas disease is an example of true unmet medical need in the U.S., if KaloBios proceeds with its proposed pricing I’m concerned the unmet medical need for Chagas will only grow.
Lastly, IDSA continues to strongly support fair and appropriate incentives to stimulate pharmaceutical innovation in areas of unmet medical need. IDSA has long championed the need for incentives to revitalize the research and development of new antimicrobial drugs to treat infections caused by multidrug resistant pathogens for which few or no safe and effective treatments currently exist. Striking balanced federal policies that support patient access and incentivize innovation to address unmet medical needs is a complex endeavor. IDSA is a committed partner with the federal government and other stakeholders in examining these issues and considering appropriate policy solutions.
 See Impax Announces Sale of Daraprim® to Turing Pharmaceuticals AG. Online at: http://investors.impaxlabs.com/Media-Center/Press-Releases/Press-Release-Details/2015/Impax-Announces-Sale-of-Daraprim-to-Turing-Pharmaceuticals-AG/default.aspx.
 See Access to Daraprim (Pyrimethamine) blog. Online at: http://hivclinician.org/pyrimethamine/.
 See Turing Reduces Cost of Daraprim® (pyrimethamine). http://www.turingpharma.com/media/press-release?headline=turing-reduces-cost-of-daraprim%2526reg%253b-%28pyrimethamine%29%250d%250a.
 See Forbes. Martin Shkreli Admits He Messed Up: He Should’ve Raised Prices Even Higher. Dec. 3, 2015. Online at: http://www.forbes.com/sites/dandiamond/2015/12/03/what-martin-shkreli-says-now-i-shouldve-raised-prices-higher/.
 See Centers for Disease Control and Prevention. Parasites – American Trypanosomiasis (also known as Chagas Disease). http://www.cdc.gov/parasites/chagas/.
 See Andrew Pollack. Martin Shkreli’s Latest Plan to Sharply Raise Drug Price Prompts Outcry. The New York Times. Dec. 11, 2015. Online at: http://www.nytimes.com/2015/12/12/business/martin-shkrelis-latest-plan-to-sharply-raise-drug-price-prompts-outcry.html?_r=0.
Carlos del Rio, MD (2015). Medical Societies Discuss Dramatic Increase In Prices For Older Medications For Infectious Diseases