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.
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.
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.
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.
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.
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
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%
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
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
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
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
“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. 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.