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.

07/20/15

Dangerous Drug Cocktails

© Claudio Ventrella | 123RF.com

© Claudio Ventrella | 123RF.com

When the largest pharmacy benefit company in the U.S. with revenues of $104 billion publishes a study of patients’ use pain medications, it gets some attention. That was exactly what happened when Express Scripts published “A Nation in Pain.” FiercePharma and The New York Times, among others, highlighted some disturbing trends with the prescribing habits of painkillers. Around 60% of the patients taking opiates were also prescribed other sedative drugs, like muscle relaxants and benzodiazepines—a great way to overdose and die.

The CDC has said that the U.S. is in the midst of a prescription painkiller overdose epidemic. Since 1999, the amount of prescribed painkillers has almost quadrupled. But there hasn’t been an overall change in the amount of pain being reported. “Every day, 44 people in the U.S. die from overdose of prescription painkillers, and many more become addicted.” In 2013, that meant more than 16,000 deaths from painkillers. These overdoses often involved benzodiazepines. Almost 7,000 people are treated in ERs each day for their misuse of prescription painkillers. The most commonly identified drugs in overdose deaths include:

  • Hydrocodone (e.g., Vicodin)
  • Oxycodone (e.g., OxyContin)
  • Oxymorphone (e.g., Opana)
  • Methadone (especially when prescribed for pain)

“A Nation in Pain” looked at 6.8 million insured Americans of all ages who filled at least one prescription for an opioid to treat either short-term or long-term pain from 2009 through 2013. Short-term users were defined as patients who were prescribed an opiate pain medication for a total supply of 30 days or less within a one-year period. Long-term users were those prescribed an opiate pain medication for more than a 30-day supply in a one-year period. Some of the key findings of their study included a decline of 9.2% in the number of Americans filling a script for opioids between 2009 and 2013 (See the graphic below).

rx-painkillers-sales-and-deaths-700wBut this decline was offset by an increase of 8.4% in the number of prescriptions filled and the number of medication days per prescription. The number of short-term users declined 11.1%, while the number of long-term users remained constant.  Nearly half (46.9%) of long-term patients continued to use painkillers for three years or longer. “Almost 50% of those patients were taking only short-acting opioids, putting them at higher risk of addiction.” Of the nearly 60% of patients noted to be using potentially dangerous and fatal drugs in combination with their painkillers, 33% were using benzodiazepines. The most common cause of overdose deaths with multiple drugs involves opioids and benzodiazepines.

A majority of patients (58.5%) were using opiate pain medications with other prescription drugs that carry safety risks when used concurrently. Among long-term opioid patients, 29.2% had prescriptions for benzodiazepines in the same month. Opioids, muscle relaxants and benzodiazepines all suppress the respiratory system. Taking them concurrently can increase these reactions exponentially.

While there could be rare instances when opioids and benzodiazepines or muscle relaxants may be appropriate to prescribe together, seeing these potentially dangerous mixtures used so commonly by such a high percentage of patients is of great concern.

Many patients were taking two or more short-acting opioids at the same time; 27.5% of the long-term opioid users were doing so. This combination of longer-term usage and concurrent usage of two or more short-acting opioids was a recipe for developing drug dependence and addiction. Of the patients taking these potentially dangerous combinations of medications, two-thirds (66.6%) were prescribed the drugs by two or more physicians. Almost 40% filled them at two or more pharmacies. Glen Stettin M.D., a Senior Vice President at Express Scripts said better coordination of care is needed to correct this problem.

People looking to abuse controlled substances will often attempt to obtain prescriptions from multiple prescribers; and fill prescriptions at multiple pharmacies. So Express Scripts has developed programs to counter the abuse by restricting certain patients to one pharmacy, and in some cases, to one prescriber. But drug addicts are nothing if not determined and ingenious. The following story may seem extreme, but with my experience working with addiction, I could see it happening.

Lynne Nowak, M.D., the Medical Director of Personal Health Solutions at Express Scripts told of a patient admitted to her hospice practice with a terminal illness. The patient was taking high doses of both short-acting and long-acting opioids, along with benzodiazepines and other medications. After gathering information and additional medical records, Doctor Nowak and her team discovered that the patient had fabricated a terminal illness and admitted himself to hospice care to get the medications.

In an appendix, Express Scripts indicated the top opioids in the U.S. according to their market share in 2013 were:

  • •Vicodin®/hydrocodone with acetaminophen (46.1%);
  • •Ultram®/Tramadol (14.7%);
  • •Percocet®/oxycodone with acetaminophen (13.6%);
  • •OxyContin®/oxycodone (8.3%);
  • •Tylenol® with Codeine/codeine with acetaminophen (3.8%).

The huge preference for Vicodin® will likely fade by 2015, as it was reclassified upwards as a Schedule II controlled substance in October of 2014. This means that there will be greater restrictions on refills. Schedule II prescriptions require a physical prescription (no pharmacy call-ins) and a face-to-face visit with the prescriber. Ultram®/Tramadol is a Schedule IV controlled substance, and I expect that we will see an increase in how often it is prescribed with the increased restrictions on Vicodin®.