06/17/16

Impeccable Timing

31118385_sTiming is everything—even with medications coming to market. In the last few years new, effective treatments for the Hepatitis C Virus (HCV) have come to market as the death rates steadily climbed. Solvadi (12/2013) and Harvoni (10/2014) by Gilead Sciences; Viekira Pak (12/2014) by AbbVie and Zepatier  (01/2016) by Merck are the main ones. They have cure rates over 90% in many cases. Although their prices have been sky high, according to the WHO, the production costs of these drugs are quite low. Harvoni prices were expected to drop, but I haven’t anything much cheaper than $94,500 for 12 weeks of medication. Viekira Pak lists at $83,300 for 12 weeks; Zepatier is the bargain at $54,600.

New CDC data in May of 2016 indicated that HCV deaths for 2014 reached an all-time high of 19,659. The rates have been steadily rising since 2010 when the total was 16,627. The CDC also stated their numbers were most likely a fraction of the deaths attributable in whole or in part to chronic hepatitis C. There are an estimated 2.7 to 3.9 million chronic cases of HCV in the U.S. New acute cases of HCV have also been steadily increasing. In 2014 there were 2,194 new cases of HCV reported, a 300% increase since 2005. The CDC suggested that actual cases are estimated to be 13.9 times higher than the number of reported cases in any year. The following chart was compiled from the CDC data.

2010

2011

2012

2013

2014

Actual 

New HCV

853

1,230

1,778

2,138

2,194

Estimated

New HCV

11,800

16,500

24,700

29,700

30,500

Cause of Death

as HCV

16,627

17,721

18,650

19,368

19,659

A study done on the CDC HCV data found that from 2003-2013 the number of deaths from HCV surpassed the combined total of 60 other infectious conditions. This was despite the improving therapies now available. The HCV death statistics could begin decreasing in the next few years, as the impact of the new drugs is felt in treatment. But the high cost of medications has resulted in health insurance companies prioritizing treatment for the worst HCV cases. So as the heroin and prescription pain medication epidemic rages on, new HCV patients have to wait their turn until their HCV gets serious enough for their health insurance to approve treatment.

Despite enthusiasm for the new curative, brief (12-week), all-oral antiviral treatments for hepatitis C virus (HCV) infection, the continued health burden and increased mortality for HCV-infected patients in the United States remain underappreciated.

A CDC press release indicated the greatest HCV burden falls on baby boomers, born between 1945 and 1965. A study published in The Lancet Infectious Diseases in 2016 suggested injection and blood transfusion technologies were not as safe as they are today, so many boomers may have been unknowingly living with HCV for many years. Jonathan Mermin of the CDC said: “Why are so many Americans dying of this preventable disease? Once hepatitis C testing and treatment are as routine as they are for high cholesterol and colon cancer, we will see people living the long, healthy lives they deserve.” The outrageous price for HCV medications may be part of your answer, Dr. Mermin.

A Live Science article on the CDC study noted that HCV is primarily spread today through people sharing needles, syringes or other equipment used when injecting drugs. “But before 1992, when the U.S. began screening the blood supply for the virus hepatitis C was also commonly spread through blood transfusions and organ transplants.” The following chart from Wikimedia Commons, composed by Opigan13, was compiled from CDC figures. It shows data on hepatitis C infection by source.

 576px-Hepatitis_C_infection_by_source_(CDC)_-_en

HCV can be a “silent illness,” with people having no symptoms for decades. This allows the disease to progress unnoticed. Hepatitis C is “a different beast” from other liver infections that have more symptoms or are shorter in duration, according to Dr. Raymond Chung, director of hepatology and the Liver Center at Massachusetts General Hospital. Dr. Chung thought the increase in HCV deaths could continue for five more years or longer.

Amy Nunn, an associate professor of behavioral and social sciences at the Brown University School of Public Health said the rise in HCV deaths was alarming. About 85 percent of individuals who are infected with HCV don’t know they have it. Most people are not routinely screened for the virus. Nunn also pointed to the high cost of the new hepatitis C drugs as one reason that some people are having trouble getting access to them in the early stages of the disease.

A report by IMS Health for 2015 indicated that nearly 250,000 new patients received treatment for HCV in 2015. Added to the 170,000 new patients in 2014, the past two years have seen 5 times the number of patients than the previous three years combined. The majority of patients were treated by Medicare (50%); followed by commercial insurance (28%) and Medicaid (19%); 3% paid cash. Non-discounted spending over the past two years for the newer HCV drugs was $31.0 billion. “The discussion continues over the price of these medicines and the criteria for determining patient access and insurance coverage.” See chart 10 in the report for this data.

Spending on HCV went from so small an amount in 2013 that a figure couldn’t be shown in chart 8, to 12.2 billion in 2014 and 18.8 billion in 2015. Looking at the top medicines by spending in 2015, Harvoni was #1 with $14.3 billion. Solvadi dropped to 19th with $3.0 billion spent. In 2014 Solvadi had been tied for 1st with Humira at $7.8 billion in spending.

The World Health Organization (WHO) estimates that 130 to 150 million people globally have chronic hepatitis C infection. Around 500,000 people die yearly from HCV-related liver diseases. The most affected regions are Africa, Central Asia and East Asia. Populations at risk of HCV include: people who injects drugs, people who have used intranasal drugs, people who have tattoos or piercings, people with HIV, prisoners or previously incarcerated individuals, and children born to mothers with HCV.

The incubation period for hepatitis C ranges from 2 weeks to 6 months. After the initial infection, 80% of people do not show any symptoms. Individuals who are acutely symptomatic could exhibit “fever, fatigue, decreased appetite, nausea, vomiting, abdominal pain, dark urine, grey-coloured faeces, joint pain and jaundice (yellowing of skin and the whites of the eyes).” The WHO said:

Recently, new antiviral drugs have been developed. These medicines, called direct antiviral agents (DAA) are much more effective, safer and better-tolerated than the older therapies. Therapy with DAAs result can cure most persons with HCV infection and treatment is shorter (usually 12 weeks) and safer. Although the production cost of DAAs is low, the initial prices are very high and likely to make access to these drugs difficult even in high-income countries.

So pharmaceutical companies like Gilead Sciences, AbbVie and Merck are making enormous profits from their HCV treatments and will continue to do so for many years (see “Riding the Hep C Gravy Train”). The low production cost for HCV drugs is also an explanation for why Gilead Sciences was so willing to offer steep discounts to countries like Egypt (See “Is There No Balm in Gilead?” and “Hepatitis Hostages”)—it’s good PR and they either still make a profit or buy a lot of goodwill for a nominal cost. As Amy Nunn said, “This is an epidemic of enormous magnitude.” And it looks like it will be around for awhile longer. Gilead, Merck and AbbVie, your timing for drug development was impeccable.

05/20/16

Riding the Hep C Gravy Train

12992431_sGilead Science launched its revolutionary drug, Solvadi to treat hepatitis C in December of 2013. At $1,000 per pill, a twelve-week course of treatment costs $84,000. Combined with some other necessary medications, the cure rate was projected to be over 90%. Then on October 10, 2014 Gilead launched Harvoni, a combination of Solvadi and ledipasir, which meant that only one pill taken daily for twelve weeks was needed. Gilead priced Harvoni at $95,000 per 12-week treatment.  Patient cure rates for Harvoni were in the mid-to high 90% range. Gilead justified its price for Harvoni and Solvadi by pointing to longer-term savings on costly complications from hepatitis C, such as liver transplants, liver cancer and repeated hospitalizations for advanced cases of Hep C. Then the company booked a ride on the gravy train.

Drawing on the annual financial reports noted in the company’s press releases, Gilead Sciences grossed $10.3 billion in sales for Solvadi in 2014; $8.5 billion of which was in the U.S. Harvoni sales in 2014 grossed $2.1 billion; $2 billion of which was in the U.S. Solvadi sales for 2015 dropped to $5.3 billion; $2.4 billion of which was in the U.S. This was likely because of the huge sales for Harvoni in 2015, $13.9 billion; $10.1 billion of which was in the U.S. Full year product sales for Gilead Sciences for 2013 was a respectable $11.2 billion, an increase of 15% over 2012 product sales. In 2014, full product sales were $24.5 billion, an increase of 137 percent. And in 2015, full product sales were $32.2 billion, an increase of 31 percent.

This was enough of a sales boost for Gilead Sciences to jump from the 21st ranked pharmaceutical company by global sales in 2013 to the 9th ranked company by global sales in 2014. This means that Gilead Sciences had an estimated 95% share of the U.S. market for hepatitis C treatment, where 3.2 million people are infected. AbbVie, the 11th ranked pharmaceutical company in 2014, launched its own hep C drug treatment, Viekira Pak, in December of 2014. There wasn’t much of a discount, as it was priced at $83, 320 for a 12-week treatment, according to Hanna Ishmael for Bidness ETC.

Express Scripts, the U.S.’s largest pharmacy benefits manager, secured a discount from AbbVie for Viekira Pak and announced it was dropping coverage for Gilead’s treatments, except under certain medical conditions. The Chief Medical Officer for Express Scripts said the discount put it in the range of Western European levels for Gilead’s hepatitis C treatment, between $51,000 and $66,000. That is correct. Gilead negotiated a better deal for its treatments with countries outside the U.S. “The dynamic will save Express Scripts customers $1 billion in 2015, with a total of $4 billion in savings across the United States when all payers and employers are included.”

In response to the deal between Express Scripts and AbbVie, Gilead began offering discounts that averaged 46% off its listed price for Solvadi and Harvoni, meaning they cost would $45,360 and $51,300 respectively. However, some payers continued to restrict access to Gilead’s drugs, so in return, Gilead began to limit enrollment in its patient assistance program for hepatitis C drugs. These programs help patients obtain Solvadi and Harvoni treatments when they don’t have the finances or sufficient insurance coverage to get the medicines. Beginning on July 1, 2015, Gilead announced that patients who were insured, but did not meet their payers coverage criteria would no longer be eligible for Gileads Patient Assistance Program. Ed Silverman said: “The drug maker is taking this step after finding that some payers, despite receiving discounts in recent months, have continued to restrict patient access to its hepatitis C medicines.”

Unfortunately, reporting for FiercePharma, Emily Wasserman said there have been reports of serious liver injuries tied to Viekira Pak, which led to changes in the meds’ labels warning doctors against using them for the sickest patients. AbbVie countered by saying that its drugs are safe for the vast majority of patients. The risk of serious injury is only for 3% to 5% of patients with the most serious stage of the disease.

The FDA and Gilead announced in March of 2015 that a serious slowing of the heart rate (symptomatic bradycardia) can occur when Harvoni or Solvadi is used in conjunction with the antiarrhythmic drug amiodarone. Nine patients had had serious reactions and one of the nine died. Three others had to receive pacemakers. Gilead said the mechanism of the potential interaction is unknown. “Gilead said that 6 cases of symptomatic bradycardia happened within 24 hours of starting one of the drugs and the other three in two to 12 days.”

Now their the competition is expanding. Johnson & Johnson has its own next-generation hep C treatments in the pipeline and Merck just had its hep C drug, Zepatier, approved by the FDA in January of 2016. Like Harvoni, Zepatier is a once-daily single-tablet of two drugs. The new drug is priced at $54,600 for a 12-week regimen, which Merck said puts it in the range of discounts for other competing hep C treatments like Harvoni and Viekira Pak.

Reportedly, Zepatier also has a better safety profile than Solvadi. Advera Health Analytics looked at the clinical trials data for all three drugs and concluded it was less risky than Solvadi. “The general conclusion is that Zepatier looks safer than Sovaldi, just based on clinical trial information.” Gilead, of course, disagrees. They said the analysis was “deeply flawed.” It wasn’t based on a head-to-head comparison of the three drugs. There wasn’t consideration given for the underlying condition for which patients were taking Harvoni or Solvadi. Nor was there adjustment made for the drugs given along with Solvadi, which have their own serious side effects.

The first-generation hepatitis C treatments take longer, have more known adverse side effects and don’t have as high of a patient cure rate. The second-generation treatments, like Solvadi and Harvoni will save lives. But patients in the U.S. are at a financial disadvantage as they are forced to pay a much higher cost for their treatment. See “Hepatitis Hostages” and “Is There No Balm in Gilead?” for more on this topic. It is getting better, but the initial gravy boat of profits launched Gilead into the top ten of pharmaceutical companies in global sales for 2014. When the dust settles from all the above noted concerns, the bottom line is that the pharmaceutical companies, especially Gilead Sciences, will make a huge profit off their hepatitis C treatments. There is a balm in Gilead, but it’s going to cost you.

12/10/14

Hepatitis Hostages

Stockfresh image by stokkete

Stockfresh image by stokkete

In September of 2014, Gilead Sciences announced a deal with seven Indian drug companies to produce less expensive generics for their blockbuster Hepatitis C drug, Sovaldi. Gregg Alton, an executive vice-president for Gilead said: “This announcement is a game-changer. . . . The great thing is we are making this medication available to millions of people around the world.” Alton also said: “Gilead is working to make its chronic Hepatitis C medicines accessible to as many patients, in as many places, as quickly as possible.” The medication could be on the market in India by the third quarter of 2015. The licensing deal will cover 91 countries, which have an estimated 100 million people living with Hepatitis C. But the cost to Americans and the profits to Gilead for Sovaldi are through the roof.

Through the third quarter of 2014, Gilead has made $8.6 billion in profit from Sovaldi (see info here, here, and here.)—most of it from American sources. It is on schedule to exceed $10 billion in sales for 2014. This is largely because of the extreme cost differential of Sovaldi to Americans. The charge to US patients is $1,000 per pill; $84,000 for a full 12-week course of treatment with the drug. In June of 2014, Forbes contributor Robert Glatter reported that Gilead was offering Sovaldi at a 99% discount to countries like Egypt and India. The production cost for Sovaldi is somewhere between $130 and $150 per pill. Gardiner Harris of the New York Times reported that Gilead will introduce the drug in India for around $10 per pill.

Rohit Malpani, of Doctors Without Borders, observed that: “Gilead’s licensing terms fall far short of ensuring widespread affordable access to these new drugs in middle-income countries, where over 70 percent of people with hepatitis C live today.” Gregg Alton said that Gilead would provide middle-income countries with discounted prices for Sovaldi. “Pricing for Thailand, Mexico or Brazil will be very different than the U.S. price.”

As early as the spring of 2014, concern was that the cost of Sovaldi in the U.S. would lead to a huge rise in healthcare costs. There are over 3 million potential customers with Hepatitis C in the U.S. PharmExec.com reported in April that a large insurer, United Health Group, reported a decline in its first-quarter earnings, in part because it spent more than $100 million on hepatitis C treatments. In July, the Senate Finance Committee informed Gilead it was launching an investigation into the pricing of Sovaldi.

Given the impact Sovaldi’s cost will have on Medicare, Medicaid and other federal spending, we need a better understanding of how your company arrived at the price for this drug.

Gilead defends the price, citing the eventual cost savings over time. “The value of a cure … is underestimated in terms of the overall advantage that the health care system receives from it.” Yet some organizations are suggesting that treatment be withheld until the condition is more serious. The problem with that is determining how far Hepatitis C has progressed can be difficult. And there is evidence that early treatment means there is a better chance of curing Hepatitis C. Also, early treatment can avoid damage to the liver from the virus.

Withholding treatment is already a reality in the California prison system. The chief pharmacy officer of San Francisco’s Public Health Department said that if they used their entire drug budget for the year, they could only treat 24 or 26 of the 108 inmates estimated to be infected with Hepatitis C.  “It’s crazy. It’s just insane. And that’s where this whole conversation about price becomes important, because at what cost?” Nationwide, at least 500,000 inmates have chronic Hepatitis C. The net costs of their treatment alone could exceed $30 billion.

Now Gilead Science has had a new treatment for Hepatitis C approved—Harvoni. It is a combination of Solvadi and the NS5A inhibitor ledispasvir. Harvoni is “the first once-daily single tablet regimen for the treatment of chronic hepatitis C genotype 1 infection in adults.” The FDA granted Harvoni a Priority Review and Breakthrough Therapy designation because of its potential to offer a major advance in tretment over available therapies. Nezam Afdhal, a principle investigator in the Harvoni trials said: “For the first time, the vast majority of patients can be cured with a once-daily pill in only eight or 12 weeks.”

The cost of Harvoni will be $94,500 for a full 12-week course of treatment. But that is roughly in line with the previous cost of Sovaldi and the drugs used with it. “Many patients should be able to take Harvoni for only eight weeks, at a cost of about $63,000.” The shorter time period can be considered for treatment-naïve patients without cirrhosis.

But the cost is still too high for many insurance companies and Medicaid programs, who are restricting the use of Sovaldi to the most seriously ill patients. Some are requiring patients to demonstrate they have not abused alcohol or illicit drugs for a number of months or limiting the treatment to “once-in-a lifetime.” Dr. Steven Miller, the chief medical officer of Express Scripts, which manages pharmacy benefits for employers and insurance companies, said: “Their budgets just are not going to be able to tolerate it.”

The small population argument justifying a high cost of drug treatment (to motivate the drug’s development) like that used for drugs like Acthar and Soliris doesn’t apply to Sovaldi and Harvoni. If every American with Hepatitis C was treated with Sovaldi, the cost would be $250 BILLION! Treating everyone on the planet would cost $14.28 TRILLION. “To put those numbers in perspective, the U.S. spent about $381 billion on prescribed medicine last year.” Gilead defended the cost of the medicine, saying: We believe the price of Harvoni reflects the value of the medicine.” The Motley Fool suggested that Harvoni could generate as much as $12 billion in its first full year on the market.

Even when factoring in the negative impacts of competition, shortened treatment durations, and the need for additional approvals, Harvoni should still double the marijuana industry’s 2018 revenue forecast by this time next year.

Gilead Sciences announced its third quarter financial results for 2014. Gilead’s total revenues for nine months ending on September 30th was $17.25 billion. This compared to $7.76 billion for the same period in 2013. $7.33 billion of the $8.6 billion in sales of Sovaldi for 2014 was made in the U.S. market.

Plain and simply, the American health care system and Americans with Hepatitis C are being held hostage by Gilead Sciences. In their pursuit of record-breaking profits from Sovaldi and Harvoni, Gilead is creating a health care crisis by refusing to negotiate a more reasonable cost to Americans. See my previous articles, “Is There No Balm in Gilead?” and I Guess I’m a Little Bit Socialist,” for more on Gilead Sciences and Sovaldi.