Gilead aims to eradicate hepatitis C from the planet and has enlisted an entire nation as its demonstration lab. In return, the Republic of Georgia has gotten the best possible price on Harvoni (ledipasvir-sofosbuvir), the company’s hepatitis C drug that lists at $1,150 a pill in the U.S.
The Black Sea nation wedged between Turkey and Russia does not pay a penny (or “tetri”) to Gilead as part of a five-year Hepatitis C Elimination Program launched in April with technical support from the U.S. Centers for Disease Control and Prevention (CDC).
Gilead donated an initial 5,000 courses of Sovaldi (sofosbuvir) and, this fall, began supplying Harvoni, which it began donating at a rate of 20,000 courses annually this fall upon its approval by Georgia.
The Georgian government is funding other costs associated with the program, such as screening, administration and monitoring. Harvoni is a once-daily tablet while patients must use Sovaldi with other medications.
With just a population of five million, Georgia has the world’s third highest prevalence of HCV infection, exceeded only by Mongolia and Egypt. As many as seven percent of the nation’s adults carry the virus, a blood infection which can destroy the liver. Worldwide, HCV infects an estimated 130 – 150 million people and killed 700,000 in 2013.
By the end of August, the Georgians had completed a population based prevalence survey, registered 10,564 patients in the program, started treatment on 3,022 and recorded cures for 122 of 125 patients completing a 12-week regimen. Some estimates place the total number of Georgians infected at 200,000.
Progress but Obstacles
Despite this early progress, the Georgians are facing obstacles inherent in the complexity of the disease and the variety of current therapies, including interferon, multiple anti-virals, Sovaldi and Harvoni. These obstacles will hinder eradication there or anywhere else – as noted by “Alexandre,” a Georgian HCV patient interviewed by Georgia Today.
“I try not to worry,” said Alexandre, “My biggest concern is that our infectionists lack experience with hepatitis C management. The disease emerged in the 80’s and despite a large number of variations in the treatment formula, it needs high professional experience.”
The virus, discovered in 1989, has six different genotypes, the prevalence of which varies from nation to nation. Genotype 1 is most common in the United States at 75% of those infected. In Georgia, genotype 1 drops to 43%, accompanied by genotype 2 at 20% and genotype 3 at 37%.
Disease progression by patient also differs, from spontaneous disappearance or easy treatment of the virus, to chronic hepatitis, cirrhosis, cancer and/or decompensated liver disease requiring a liver transplant. Patients can also vary by age, comorbidities (e.g. heart disease, HIV), treatment history, risk factors and disease stage. Hepatitis C can also be associated with heavy alcohol use, toxins, some medications, and certain medical conditions.
As a result, selecting the right treatment alternative typically requires – even in the United States — a specialist to type the virus, assess the patient, avoid harmful drug-drug interactions and monitor for potential side effects. “Alexandre,” for example, suffered an allergic reaction from a prescribed adjunctive medication, ribavirin. Patients must also strictly adhere to their medications or risk full recovery.
In the United States, the National Institutes of Health (NIH) is conducting a clinical trial in Washington, DC, to assess the effectiveness of treating hepatitis C with Harvoni in community clinics led by primary care physicians, nurse practitioners, and physician assistants. Based on trials conducted by specialist teams, the Food and Drug Administration (FDA) approved Harvoni in October 2014, but only for genotype 1; approval for genotypes 4, 5 and 6 came in November 2015.
Miracle Cure for Hepatitis C
However, a solution for the specialist bottleneck is on the way — the first all oral, single tablet chronic HCV regimen for every genotype, simple to use regardless of prior treatment, disease stage or anti-viral resistance. Potential side effects are modest, most commonly fatigue, nausea and headache. “This is what a miracle looks like,” enthused one hepatitis C activist on Twitter.
Groundbreaking results from clinical studies of Gilead’s sofosbuvir (Sovaldi) – velpatasvir (SOF/VEL) combination recently appeared in the New England Journal of Medicine here, here and here, and in the Annals of Internal Medicine here and here.
The new drug is on approval fast tracks in both the U.S. and Europe. The FDA has assigned SOF/VEL a Breakthrough Therapy designation as an investigational medicine that may offer major advances in treatment over existing options. It has also set a PDUFA approval target date of June 28, 2016. Meanwhile, the European Medicines Agency (EMA) has granted SOF/VEL Accelerated Assessment.
“This drug regimen changes the standard of care in treating patients with HCV. We can now cure almost everyone with a very simple treatment,” explained Dr. Jordan Feld, MD, MPH, lead author of the NEJM studies, to the Toronto Star.
“Knowing which treatment to use for which patient required expertise, which made it much more difficult for non-specialists to treat hepatitis C. With the single tablet that is effective for all strains of the virus, it’s hoped that family doctors, internists and nurses will step in to treat hepatitis C,” he added.
“There are some who believe that the future is a one-size-fits-all single pill, such that a primary care doctor could prescribe it without having to be concerned about genotype, viral load, or complications,” concurred Ronald Sokol, MD, of University of Colorado School of Medicine and Children’s Hospital Colorado during a liver disease conference in November 2015.
Weighing in, too, were two key CDC leaders via a NEJM editorial: John Ward, MD, Director of the Viral Hepatitis Program and Jonathan Mermin, MD, MPH, Director, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP). They said sofosbuvir–velpatasvir regimen could simplify HCV management, “paving the way for simple ‘test and cure’ strategies appropriate for primary care and other settings, such as addiction-treatment programs.”
In noting that this new medicine removes significant clinical obstacles to hepatitis C eradication on a global scale, Ward and Mermin are very concerned that financial and access barriers could be thwarting:
“The availability of simple, safe, and curative regimens creates opportunities for improving the health of the millions of patients living with HCV infection. At a population level, the effect of HCV medications will be determined by affordability and equitable access to HCV testing, care, and treatment. Only through these improvements can our focus be directed to what matters most: reducing the morbidity and mortality associated with HCV infection, stopping HCV transmission, and ultimately eliminating HCV as a public health threat in the United States and worldwide.”
Pricing the Miracle Cure
How do you price a new miracle cure for hepatitis C, serving both shareholders and patients? Gilead likely is still working the problem, deploying a process much like the one it used to price Sovaldi. The U.S. Senate Finance Committee revealed the process in a December 2015 report, which the Wall Street Journal described as providing “perhaps the most transparent look ever into pricing decisions in the modern drug business.”
Aside revenue maximizing accusations and price gouging insinuations by Sens. Ron Wyden (D-OR) and Chuck Grassley (R-IA), Gilead actually deployed a very deliberate pricing process. It calculated the value added by Sovaldi compared to existing treatments and balanced that with forecast of patient “starts” (volume), potential payer access restrictions and clinical obstacles like the specialist bottleneck.
Then, amidst U.S. market competition and payer resistance for 2015 sales, it discounted both Solvadi and Harvoni by an average of 46% to an estimated $643 per tablet for Sovaldi and $536 per tablet for Harvoni.
In Europe, Gilead negotiated a $536 per tablet price for Sovaldi with both Germany and France, although the deal with France includes volume incentives. Globally, list and negotiated prices tracked a nation’s ability to pay, as measured by gross domestic product, gross national income and health expenditure per capita.
Meanwhile, Gilead has signed licensing agreements with 11 Indian generic manufacturers to produce and distribute generics for Sovaldi and Harvoni in 101 developing countries. In addition, it has signed agreements with three companies in Egypt and Pakistan for local distribution within those countries.
In May 2015, Médecins Sans Frontières/Doctors Without Borders (MSF) reported that one of the Indian generics makers was charging $189 per 28-day-supply bottle, or $567 for a full 12-week treatment course of sofosbuvir (Sovaldi). However, it is unhappy with Gilead’s generic licensing strategy, saying that it prohibits licensees from selling in 50 middle-income countries and excludes additional generics makers who want licenses.
Setting the Stage for Launch
Notably, Gilead has already included its breakthrough SOF/VEL combination drug in these generic licensing arrangements, anticipating approvals from the FDA, EMA and regulatory bodies elsewhere. Alluding to SOF/VEL and its forthcoming launch, MSF notes, “People living with HCV and governments around the world have high expectations.”
However, MSF suggests governments do not have to wait for “patent and regulatory barriers” to come down, especially in middle-income countries. To secure access to affordable treatment, MSF advises:
“Through measures taken at the domestic level, or through collective engagement at the international level, low-cost generic medicines – which cost a fraction of the high prices charged by Gilead – could be provided.”
Already, another group, Initiative for Medicines, Access & Knowledge, is challenging Gilead patents or patent applications in China, Argentina, Brazil, Russia and Ukraine.
The Republic of Georgia is among the 50 middle-income countries MSF wants included in Gilead’s voluntary licensing program – “or else.” Rather than expand its licensing program to these countries, Gilead reveals a different strategy with its Georgian demonstration project – one of engagement with these nation’s governments coupled with financial assistance from multilateral organizations.
“We will take the Georgia data to other countries around the world to really make the case that investment can fundamentally change the disease over time,” explained Gregg Alton, Gilead’s executive vice president, corporate and medical affairs. “Gilead cannot cure hepatitis C globally on our backs alone.”
Launching the Miracle Cure
Just another pharmaceutical product launch, SOF/VEL will not be. Instead, look for Gilead to announce a global campaign to eradicate hepatitis C, answering the global call of patients, health systems, governments, multilateral organizations and even the Economist newspaper.
Photographs will show generics produced and ready to ship, videos will document compelling patient stories in Georgia, agreements will chart the expansion of Georgia-like demonstrations and support from multilateral organizations. Perhaps, even MSF and Gilead leaders will stand together at the press conference.
In the U.S. and the developed world, shifting to a primary care screen and treat model, removing the specialist bottleneck, should provide an increase in patient starts justifying list and negotiated prices much lower than those of Sovaldi and Harvoni.
Watch, too, for the rollout of education campaigns to increase screening and diagnosis, and special initiatives in prisons and among substance abusers, recognizing that about half of all those with HCV have yet to be diagnosed. Again, at the press conference, expect representatives from government, medical societies and the big pharmacy benefit managers to stand with Gilead.
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