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CVS: One In 12 Hepatitis C Patients Not Adhering To $1,000/Day Pill

I am currently receiving nearly one email a day from people who have used Sovaldi who have either relapsed or have what are described as serious continuous negative side effects.

These side effect range from sight impairment, serious nonstop headaches, extremely low platelets, pancreatitis, shacking, very similar to Parkinson’s disease, dry and breaking nails, dry hair, so dry that it cannot be corrected. Some have told me there hair started turning gray half way thru treatment and started falling out. The list goes on.

Most however become non detected but with some brutal side effects never mentioned in any of the trials. I believe that this is due to the fact that when selecting individuals for the trials they only select the healthiest people. I have seen this in my practice, only the healthiest people are selected, ones with some difficulties, even slight problems, they are left out.

The main groups that I see that are relapsing are people who used Pegasus and Peg intron and people with advanced cirrhosis. It seems so far that people who used interferon Alfa 2 B only do well and people who have used my program and never used interferon do far better.

Gilead sure painted a picture  of a complete cure, no problems, only $ 1000 a pill and they gracefully left out the negatives. Certainly nothing seen yet as horrible as interferon but there may be some serious issues.

In health,
Lloyd Wright

Over 8 percent of hepatitis C patients taking Sovaldi (sofosbuvir; Gilead) are failing to complete their full, 12-week course of drug therapy, a dropout rate roughly four times that observed in clinical trials.

By discontinuing the drug, shown to have a 90+% cure rate, these patients (and their insurance providers) are incurring health care costs of $28,000 or $56,000, without knowing if they are rid of the virus.

Whether such patients will have to restart a complete 12-week course of the $1,000 per day pill remains a question for medicine and pharmacy experts. (The lowest, discounted retail price I could find in my neighborhood is $1,056/pill, via GoodRx.)

This real-world data comes from an analysis released this morning by CVS Health Research Institute, led by Troyen Brennan, MD, MPH, executive vice president and chief medical officer of CVS Health.

Dr. Brennan and William Shrank, MD, the company’s chief scientific officer, published a viewpoint article in JAMA last month, offering perspective on the high price but remarkable benefits of Sovaldi. Previous interferon-based therapies offered a 40% cure rate.

Sovaldi is the first of several drugs specifically targeted to the hepatitis C machinery that replicates its RNA genome (the NS5B polymerase, in this case).

The costs of the drug are amplified by the patient population itself. In the U.S., hepatitis C infects between 3.4 to 4.4 million people, with another 0.5 to 1 million among the homeless and incarcerated, according to NHANES data. According to Gilead’s security filings, only about 80,000 patients in the U.S. and Europe have started on the drug, reports Jaimy Lee at Modern Healthcare.

Much attention has been paid to the costs of treating this large population with Sovaldi and the potential for it to increase individual health care coverage by $200 to $300 per year.

But less attention has been spent discussing the cost savings from precluding the need to manage the cirrhosis and liver cancer caused by the virus, as well as the costs of liver transplants.

I asked Dr. Brennan why they chose to post today’s report as a white paper on the CVS Health site rather than run it through peer-review for JAMA or another medical or pharmacotherapy journal.

“It’s fairly straightforward and represents analytics of our utilization data that are looked at all the time,” said Brennan. “The other thing is that it’s very topical right now and if we waited six weeks to six months for review and publication by a leading journal, it might not be as topical anymore.”

In addition, the study is freely-available here as a PDF, as opposed to behind a paywall as with their August JAMA article.

Far less aversive than interferon

Together with Alan M. Lotvin, MD, executive vice president of the CVS Health’s specialty pharmacy arm, the team sought to determine Sovaldi’s adherence and completion patterns in patients, now that the drug has been released for use in the general hepatitis C population for about nine months.

They also assessed the factors that might influence discontinuation of Sovaldi and what type of pharmacy services the patients were provided.

For example, a known risk factor for discontinuation of drugs prior to Sovaldi is being new to therapy. Those treated previously and not cured are likely to be sicker and more motivated to complete the full course of the new drug.

In the web excerpt of his book, The Upside of Irrationality, Duke University behavioral economist Dan Ariely wrote of his personal experiences with interferon. Ariely had contracted hepatitis C from infected blood transfusions he received while being treated for severe burns after a military training accident.

The initial protocol called for self-injections of interferon three times a week. The doctors advised me that after each injection I would experience flu-like symptoms, including fever, nausea, headaches and vomiting. But I was determined to kick the disease, so every Monday, Wednesday, and Friday evening for 18 months I plunged the needle deep into my thigh. About an hour later the nausea, shivering and headache would set in.

Every injection day was miserable. I had to face giving myself a shot followed by a 16-hour bout of sickness in the hope that the treatment would cure me in the long run. I had to endure what psychologists call a “negative immediate effect” for the sake of a “positive long-term effect”.

And that was for a drug that, with ribavirin, had no more than a 40 percent cure rate, even for an 18-month course. After such an experience, an oral, once-daily medicine for 12 week with a 95 percent cure rate would be far more welcomed by a patient undergoing this experience relative to a treatment-naive patient.

So why do patients stop taking the drug?

Since Sovaldi was approved last December, the CVS/caremark pharmacy benefits management service has filled 16,560 prescriptions for the drug. More than 65 percent of these patients received the new drug without other currently used drugs such as ribavirin and pegylated-interferon alfa interferon. Forty-three percent took Sovaldi and ribavirin while 23% took Sovaldi plus Olysio.

The team pulled out the data for 1,965 hepatitis C patients with at least 44 months of drug therapy information for analysis. Those who had received previous therapies could then be compared with those receiving Sovaldi as their first drug for the disease. As with previous drugs, 8.7 percent of treatment naive-patients discontinued Sovaldi while only 5.3 percent of the previously-treated patients stopped the drug prematurely.

For patients taking Sovaldi with other medications, the discontinuation rates were up to four-fold higher than those observed in clinical trials (2.0 to 3.6 percent. Those taking Sovaldi with with peg-interferon and ribavirin discontinued at a rate of 10.2 percent while 9.0 percent of those taking Sovaldi and ribavirin did not complete the full course.

The best adherence, a 4.3 percent discontinuation rate, was observed in patients taking Sovaldi with Olysio (simeprevir), the Janssen/Johnson & Johnson NS3/4A protease inhibitor approved in November 2013.

Specialty pharmacy services

Because CVS/caremark is the nation’s second largest pharmacy benefits manager, they have access to information for patients using non-CVS pharmacies. The team was able to show that discontinuation was higher in patients using non-CVS pharmacy services (8.5 percent) than CVS specialty pharmacy services (5.9 percent).

The reason underlying the difference is a bit of a mystery because other pharmacy chains offer specialty pharmacy services for patients like those with hepatitis C. For example, CVS Specialty Pharmacy offers 24/7 telephone access to trained staff, including pharmacists, that provide disease education and drug counseling as well as help in navigating insurance issues.

But even when broken out, non-CVS speciality pharmacies faired only slightly better than standard, non-CVS retail pharmacies (8.3 percent discontinuation vs. 8.8 percent).

Brennan didn’t really trumpet this result as much as I might have expected, but did make a general point about the economic value of specialty pharmacy services and how CVS deploys their program.

“It’s a matter of expert pharmacists keeping up with the patients, making sure that they’ve refilled the medicine, as well as automated adherence signaling. It’s a high-touch approach, and that’s what specialty pharmacies do. We’ve also integrated this specialty expertise into our retail settings so they can still enroll in the specialty pharmacy program.”

“With these drugs, even low levels of adherence are extremely expensive,” says Brennan.

That holds for the cost of the ineffective drug stopped prematurely plus the likelihood that it or another expensive drugs will have to be prescribed in the future.

The main takehome point of the CVS Health study is that we need to look more closely at drug adherence in the community setting, not just for disease management, but for cost containment as well.

As Dr. Brennan says, “In the clinical trials, the discontinuation rates were in the 2 to 3 percent range, but things are never like that in the real world.”

The clinical trial process is tightly controlled, has more intensive participant follow-up, and patients are generally more motivated.

Waiting for “The Next Big Thing”

Already, prescriptions for Sovaldi have plateaued and are decreasing in what appears a pharmaceutical version of the Apple effect: doctors may be holding out prescribing Sovaldi until an even more effective combination product is expected to be approved later next year.

Beginning December 2013, when Sovaldi first became available, there was a massive rush to use the medication, with increasing numbers of patients beginning treatment each month (Figure 1). This was due to the fact that in the months leading up to the Food and Drug Administration’s approval of Sovaldi, many patients with Hepatitis C who were not experiencing symptoms or adverse health effects had delayed pursuing any treatment until the new, highly effective drug became available. In contrast to the rapid uptake observed initially, CVS Health data show a plateau and then a downward trend in the number of new starters of Sovaldi during May – August 2014. Vertex has announced that Incyte sales will cease in the U.S. in October 2014.


Beginning December 2013, when Sovaldi first became available, there was a massive rush to use the medication, with increasing numbers of patients beginning treatment each month. This was due to the fact that in the months leading up to the FDA approval of Sovaldi, many patients with hepatitis C who were not experiencing symptoms or adverse health effects had delayed pursuing any treatment until the new, highly effective drug became available. In contrast to the rapid uptake observed initially, CVS Health data show a plateau and then a downward trend in the number of new starters of Sovaldi during May – August 2014. Vertex has announced that Incivek sales will cease in the U.S. in October 2014.

Dr. Brennan calls this the “warehousing” of patients. When patients are hepatitis C-positive but aren’t yet showing severe symptoms, the slow-moving nature of the disease causes some hepatologists to hold off beginning expensive drug treatments.

“Hepatologists will tell these patients, ‘Wait, you’re not progressing. we’re not going to treat you now, we’re going to wait until these better medications are out,’” says Brennan.

Most are awaiting Gilead’s fixed-dose combination drug: sofosbuvir from Sovaldi and a newer agent, ledipasvir, that targets the NS5A protein involved in hepatitis C viral replication. This combination will only be for patients with the genotype 1 version of the viral infection, but it represents 75 percent of all hepatitis C patients. The drug course will only be for eight weeks and phase 3 trials suggest cure rates of over 95 percent.

Gilead hasn’t offered a specific price yet but Reuters is reporting a $95,000 price for the eight-week course. The FDA action data on Gilead’s filing is October 10.

For more health and pharmaceutical news and commentary, follow me on Twitter @DavidKroll, here at Forbes.com, or by clicking “Follow” on my Facebook.