One cancer drug alone could wipe out Canada’s total budget of $12B for prescription drugs. Can this last?

Drug companies bringing out new targeted therapies for rare disorders are asking, and getting, eye-popping prices. Examples include Kalydeco® for one type of Cystic Fibrosis, reported to cost CAD$300,000 per year, or the recently marketed Solaris® for which Alexion tried to get CAD$700,000 per year for Canadian patients (even higher than it was charging U.S. patients). Drug companies argue that these costs are justified because the drugs are showing dramatic results for patients. But because these are for a very small number of patients, and only a few have been marketed so far, our healthcare system may be able to absorb the cost – there are only 90 patients in Canada that might benefit from Solaris, for example. But this won’t always be the case – there are 7,000 rare disorders that may be amenable to drug treatment, and treatments are typically needed life-long.

What really brings it home are the escalating prices for some new targeted therapies for cancer.

Prominent oncologist Dr. Leornard Saltz of the Memorial Sloan Kettering Cancer Center took aim at these at the recent American Society of Clinical Oncology (ASCO) meeting. At the plenary speech, Dr. Saltz focused on the expected high cost of new combination treatment for metastatic melanoma from Bristol-Myers Squibb Co. Although he welcomed the arrival of a “truly, truly remarkable” new therapy, “he said that combining the drugs would cost around $295,000 a patient over nearly one year, which he called unsustainable. If all U.S. patients with metastatic cancer took drugs priced at $295,000 a year, it would cost $174 billion to treat them all for just one year” reports the Wall Street Journal.

Given that Canada’s total public spend on prescription drugs is about $12B, and adjusting for Canada’s population size, that would pretty much wipe out Canada’s total budget for prescription drugs.

Not all new drug pricing seems so far out of line. Although the recently released Hepatitis C drug Harvoni® costs over $1,000 per pill, and a complete course of treatment costs approximately CAD$85,000, this is a one-time treatment with near 100% cure rate for a potentially lethal disease with a very high cost burden (see our July 2015 article about this new treatment). And as outlined in an accompanying article, “Can personalized cancer care be cost-effective?” selecting the best targeted treatment for a patient’s cancer by genetic analysis of their tumour has been shown to be both cost effective and to give better outcomes.

The focus needs to be on how to appropriately price new drugs. The CBC looked into the Solaris story, pointing out that the cost of such drugs has little to do with the development and manufacturing costs. The CBC article also pointed out that much of the basic discovery costs came out of the public purse in the form of academic research funding, which drug companies do not factor into their pricing. Barry Werth of the MIT Technology Review looked into the high prices for two new drugs, Kalydeco® and Zaltrap®, and cites veteran drug maker and former Genzyme CEO Henri Termeer as saying “In determining the price for a drug, companies ask themselves questions that have next to nothing to do with the drugs’ costs. It is not a science […] It is a feel.”

Two efforts underway in Canada should help realign drug pricing. Ontario’s MaRS EXCITE program helps companies develop the evidentiary bundle, including an economic analysis, that a company can bring to the bargaining table to provide a more rational approach to drug pricing. The project “PACE-‘Omics,” led by Alberta’s Drs. Christopher McCabe and Tania Bubela, funded by Genome Canada, aims to develop better decision-making tools “to give policymakers and investors the tools they need to make the right investment decisions on technology development, regulatory pathways, cost-effectiveness and benefit to the Canadian healthcare system.” Together these approaches should help bring a better informed approach to establishing sustainable prices for new drugs.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Network

A study of personalized cancer care in action found that this approach not only saved money but resulted in better outcomes. Such personalized cancer treatment is available here in Ontario.

A small study by Intermountain Healthcare, in Salt Lake City, compared the costs of using personalized medicine in cancer patients with late stage, metastatic disease. Patients whose therapy selection was based on next-generation tumour profiling testing rather than using standard chemotherapy options have lower costs per week and longer progression-free survival.

Personalized approaches to cancer treatment are being tested at many centers, including Ontario’s Princess Margaret Cancer Centre, which launched the “IMPACT” trial (for “Integrated Molecular Profiling in Advanced Cancer Trial”) in March, 2012. This trial is described as “the first Canadian comprehensive molecular profiling program that seeks to provide doctors with specific cancer gene information so that each patient’s treatment can be tailored to his/her specific form of the disease” and aims to test 1,000 patients.

Intermountain Healthcare has been offering a similar type of test, a 98-gene cancer panel test for genes commonly altered in solid tumours. The test involves sequencing over 1200 regions of these 98 genes. The results can be used to identify the appropriate targeted therapeutic specific to the genetic profile of a patient’s tumour. In a retrospective matched cohort study of 72 patients with metastatic cancer, patients at Intermountain Healthcare that received the gene panel test had an average progression-free survival of 22.9 weeks compared to 12 weeks for the group that received standard chemotherapy treatment. The respective costs per week were slightly lower in the gene panel group, at US$3,204 vs. US$3,501. The $6,000 price of the test was included in the cost analysis.

The key contributors to the costs in chemotherapy arm “were more and longer hospital stays and emergency room visits.” In addition to avoiding such hospital visits, “targeted therapies offer other benefits. Many of the targeted drugs are oral agents, which allow patients to take them at home or work, while continuing to be productive at work and go about their daily life. They don\’t have to take time off work to go into the hospital for chemotherapy treatment” according to the authors of the study. These ancillary benefits were not factored into the above cost analysis, suggesting that the overall cost benefit is even higher.

Full details of the Intermountain Healthcare study are yet to be released (the work was presented in abstract form in conjunction with the recent annual meeting of the American Society of Clinical Oncology). Yet they suggest that the promise of personalized medicine of reducing costs while improving care can be realized. A key influencer of this, however, will be the cost of targeted therapeutics. As discussed in the accompanying article “Rising prices for new targeted therapeutics threatens their own success” new approaches are needed to ensure that high costs don’t derail the potential of personalized medicine.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Network

Genetic testing of drug metabolism genes may help personalize the selection of antidepressant medication. While not quite coming out to recommend the testing itself, an expert panel has recommended the use of such test results if they exist.

An expert panel has just released guidelines on how to use genetic information when prescribing the most widely used class of drug for the treatment of depression and anxiety, the “Selective Serotonin Reuptake Inhibitors” (SSRIs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) analyzed the published literature from genetic studies and provided dosing recommendations for drugs such as citalopram (Celexa® or Cipramil®) or sertraline (Zoloft®) based on a patient’s drug metabolism genes.

Drug metabolism genes such as the cytochrome P450 genes have long been known to influence the activity of drugs as well as potential side effects. Depending on the particular types of these genes an individual has inherited, and the particular metabolic pathway each drug undergoes, different drugs may be under- or over-active, or even potentially harmful. However the use of such genetic (or what is called “pharmacogenetic”) information to guide drug selection and drug dosing has not yet entered routine clinical use. This is despite the fact that, according to the Personalized Medicine Coalition, SSRI anti-depressants are ineffective for an average of 38% of the people they are first prescribed for, resulting in a lengthy trial and error process to find the most effective option for each patient.

The CPIC panel’s recommendations are an important but cautious step towards the routine use of pharmacogenetic information for the care of mental health patients – important in the release of guidance about how to use such genetic information if it exists, but cautious in that the panel did not have sufficient validation and cost-effectiveness studies to make recommendations about whether clinicians should order the genetic testing itself.

An important study is underway at the Center for Addiction and Mental Health (CAMH) that may help provide such evidence. Patients participating in the IMPACT Study (Individualized Medicine: Pharmacogenetic Assessment & Clinical Treatment) are offered a saliva-based genetic test to identify which antidepressant or antipsychotic medications will work best for them. Clinicians receive an easy-to-interpret report listing drugs in three categories (Green – use as recommended, Yellow – use with caution, Red – avoid) to help determine which drug, and which dose, is most likely to be most effective. So far over 3000 patients have been enrolled. Studies such as this will help contribute to real world cost-effectiveness data that a future CPIC panel could use when considering recommendations for the pharmacogenetic testing itself of patients.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Networ

Your Hepatitis C infection could be cured – if you knew that you had it.

Ontario recently approved reimbursement of the drug Harvoni® for treatment of the Hepatitis C (HCV) genotype 1 virus. Harvoni® “offers cure rates between 94 and 99%, reduces the incidence of side effects and shortens the duration of treatment to as little as eight weeks” reports the London Free Press. Over 75% of HCV cases in Canada are the genotype 1 variant, according to a recent study.

Harvoni® is part of a new class of HCV drugs called “direct-acting” antivirals that target specific steps in the HCV life cycle. Like “targeted therapeutics” for cancer treatment, these drugs have come out of a better understanding of the molecular basis of the disease. Harvoni® combines two of these direct acting antiviral drugs for greater efficacy. At the moment, Harvoni® is approved in Ontario for only those with late stage disease – those facing death or a liver transplant.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to cirrhosis, hepatocellular carcinoma and liver transplantation. An Ontario study found that the disease burden of Hepatitis C exceeds that of all other infectious diseases. The disease can progress silently and many don’t know they have the disease until late stage symptoms appear. Over 32,000 deaths are predicted amongst HCV-infected individuals in Canada over the next twenty years from liver-related causes. With new drugs like Harvoni® perhaps many of these deaths can be prevented.

The problem is that half or more people with Hepatitis C don’t even know they have it, according to the Canadian Liver Foundation. And, like Karen Robson, featured in a recent Toronto Star article, not everyone who has Hepatitis C falls into the high risk categories such as injection drug users who are routinely screened for the disease.

The Centers for Disease Control and Prevention (CDC) recommends routine screening of the “baby boomer” cohort in the USA, those born between 1945 and 1965. This is because this group carries a higher risk of Hepatitis C and accounts for 75% of cases. In contrast, screening in Ontario is restricted to certain high-risk groups such as injection drug users.

There have been recent calls for a similar baby boomer screening program in Canada. However, Canadian experts disagree on what percent of carriers in Canada know their status. Reported estimates range from 79% (reported by the Public Health Agency of Canada) down to 30% (Statistics Canada report). If it is true that most people know their status, then investing in population-level screening will have less impact. Recent recommendations from the Canadian Association for the Study of the Liver include a call for a large-scale population survey “to accurately define the prevalence of Hepatitis C in Canada.” This may lead to more comprehensive screening, and now even the possibility of a cure.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Network