October 25, 2018 – A new pharmacogenetic test called RightMed from OneOme has come to Europe, offering the possibility of eradicating the high number of deaths from Adverse Drug Reactions (ADR), as well as saving billions of dollars in the prescribing of drugs which have no effect. Co-founded by Mayo Clinic, the leading hospital in the United States, a European partnership was announced in Zagreb last week, with Leading Hospitals of the World member, St Catherine Speciality Hospital in Croatia the chosen European partner for the introduction of the OneOne RightMed test in Europe. After the press conference at St Catherine’s, Professor dr. sc. Dragan Primorac kindly agreed to an interview with TCN to tell us more.
1. Last week, St Catherine Specialty Hospital in Croatia announced a partnership with OneOme, co-founded by Mayo Clinic, to increase pharmacogenetic testing in Europe. Explain firstly what pharmacogenetic testing is, and why it is important?
Individualized (personalized) medicine can add tremendous value to health care. The United States Food and Drug Administration views personalized medicine as an innovative approach to disease prevention and treatment that takes into account differences in patients’ genes, environments and lifestyles. Pharmacogenetics is a critical component of personalized medicine. With the advances in molecular biology and genetics, pathogenesis of many diseases has been traced to variations in the genome.
The ultimate goal of pharmacogenetics is to understand how genetic makeup determines drug action and adverse reactions. Most drugs are broken down (metabolized) by enzymes. In some cases, metabolism deactivates an active drug fully or partially. In other cases, metabolism activates an inactive (or less active) drug. Different genetic variants of a particular enzyme can metabolise a particular drug or group of drugs differently; hence, understanding the particular variant in the particular patient can directly affect the decision on the drug choice and dosage. To avoid drug-drug interactions, the decision on which drug to prescribe may also be influenced by other drugs taken. Understanding the genetic basis of patient’s metabolic differences (i.e., patient’s pharmacogenetics), clinicians can select the most effective drugs while keeping the likelihood of adverse reactions at the minimum. The likelihood of drug overdose can be decreased, as the dosage is based on the genetic constitution of the patient rather than on his/her body weight and age, as in the conventional approach. Pharmacogenetics will surely become part of standard considerations in the use of pharmaceuticals.
https://www.youtube.com/watch?v=w4yvHwwrqp4
2. Two interesting facts from the press conference for me were that Adverse Drug Reaction (ADR) was the fourth biggest killer in the United States and that about 50% of administered drugs have no effect, two statistics which are costly in terms of loss of life and money. Let’s fantasise – if the OneOme RightMed test was standard practice in the United States, what impact would that have in a reduction of ADR deaths and dollar savings annually?
The first article addressing your question was published in JAMA in 1998 estimated that in 1994 overall 2 216 000 hospitalised patients had serious ADRs and 106 000 had fatal Adverse Drug Reaction (ADRs), making these reactions between the fourth and sixth leading cause of death. However in a recent article published by Light it is estimated that in the United States, adverse drug reaction (ADRs) is the fourth leading cause of death, and it is estimated that prescription drugs are responsible for 2.74 million ADRs and 128,000 deaths annually. Some other publications emphasising that ADRs cost $136 billion yearly—more than the total costs of cardiovascular and diabetes care—and cause one out of five injuries or deaths per year to hospitalised patients.
https://www.youtube.com/watch?v=6kQhLZhc0Xs
3. This is very new technology. Can you give us a real-life case study where the PGx has been used to improve a patient’s health and change medication?
There are numerous of publications precisely describing how PGx could improve a patient’s health and how it could help in reducing ADR and loss of money. I will mention just a few studies: A Mayo Clinic study involving 3,600 subjects showed that hospitalisation of heart patients was reduced by 30 percent when doctors were made aware of the pharmacogenetics data prior to treatment with warfarin. Another study has shown that the breast cancer therapy guided by a commercially available PGx test was able to achieve a cost savings of $2,256 per patient, as a result of the reduction in the use of chemotherapy.
Mrazek and colleagues recently published that patients with treatment-resistant depression have been estimated to cost the United States close to $50 billion more per year than if those same patients were to respond to first-line antidepressants. The FDA-approved drug label for codeine states in a black box warning that respiratory depression and death have occurred in children who received codeine following a tonsillectomy and/or adenoidectomy and who had evidence of being CYP2D6 ultra-rapid metabolizers. The label also states that deaths have occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were CYP2D6 ultra-rapid metabolisers, etc…
https://www.youtube.com/watch?v=CmTrtZKw_Uo
4. Take us through the practical process. I make an appointment at your clinic to take the test. What does the test actually entail and what happens next? The RightMed comprehensive test, co-developed with Mayo Clinic, determines how the patient may respond to medications, based on patients’ DNA. How does the RightMed test work?
First you make an appointment at St. Catherine’s and after a short conversation with a clinical representative at St. Catherine Hospital a physician orders the OneOme RightMed test. Then your sample is collected by using a buccal swab collection procedure.
Immediately afterwards, OneOme processes your sample and generates your RightMed test report. Finally, you visit a clinical representative at St. Catherine Hospital who helps you understand the test results. Depending on your genes, your body may break down a drug too slowly or too quickly. If you metabolise a drug too slowly, you may be exposed to too much of it, which may result in an adverse drug reaction (ADR). If you metabolize a drug too quickly, you may not get enough to have any effect at all. A OneOme RightMed test helps to identify this for your doctors.
5. Our bodies are constantly changing. Is the RightMed test a ‘snapshot’ of the current situation, or something that is valid for a longer time and/or other conditions? In other words, is it something you would recommend repeating in a few years for people seeking medication again?
PGx testing using the RightMed platform can benefit everyone, as it provides life-long information about how an individual metabolises more than 350 medications. What we like about the RightMed platform is that test reports are automatically updated as clinical guidelines change or as new evidence emerges in the future. That being said, the RightMed test will be highly recommended for polypharmacy patients (those on >5 medications) as well as those taking medications for pain management.
https://www.youtube.com/watch?v=4fcDTZ7gNmE
6. Coming from such a leading health source as Mayo Clinic, the OneOme product cannot be cheap. What does it cost, and what is included in that price?
Back in 2001, the first copy of the human genome was published sequencing a single human genome came with a $100 million price tag, making the cost of genome sequencing one of the biggest barriers to incorporate it into routine medical care. Than geneticists, physicians, agreed that we should achieve $1,000 as the magic number in order to make genetic tests affordable enough to be a part of routine health care. We believe, we achieve it and the cost of OneOme RightMed test is 4 900 kunas (approx $750).
7. The long-term goal must be to have the OneOme RightMed test as part of national health strategies. While the benefits financially are clear from the numbers mentioned above, getting countries to proactively use (and pay for) the service will be a challenge to get established. What is your strategy in this regard?
It’s only a matter of time before pharmacogenomic testing becomes standard of care so now is the time to consider how we will implement it: from educating our clinical teams, to integrating PGx information into electronic health records. There is mounting clinical evidence supporting the clinical utility of pharmacogenomic testing across multiple indications, so choose a platform that will provide clinical benefit to as many patients as possible. Most importantly, choose a PGx testing provider who has a credible clinical development team and a product that is rooted in sound clinical evidence.
In order to help those leaders to understand a great benefit of pharmacogenetic, recently I was editing (together with Prof. Hoppner) a book entitled Pharmacogenetics in clinical practice where we underline how pharmacogenomics as a critical component of personalized medicine will help in optimal treatment that takes into account differences in patients genes, environments and lifestyles.
8. The RightMed test will be available in Europe initially in Croatia via your hospital, before expanding to Germany and Switzerland, according to the press conference. Can you tell us more about that?
St-Catherine Hospital sees more than 35,000 patients per year, so we wanted to implement a test that could be applied to a number of specialty areas, including pain, cardiology, psychiatry and cancer. The comprehensive nature of the RightMed panel was therefore also a critical factor in our decision. In addition, we chose to work with OneOme because of the scientific rigor which was applied to the development of the RightMed platform. Their PGx interpretation is supported by the highest level of clinical evidence, making their test the most clinically actionable one on the market. 9. Some people may be surprised that a Croatian hospital was chosen as the European partner for such a highly specialised medical initiative. St Catherine Speciality Hosptial is a member of the Leading Hospitals of the World, as well as the hospital for, among others, Croatia’s World Cup heroes. For those international readers who have not come across your hospital, tell us about St Catherine Specialty Hospital, your long association with Mayo Clinic, and how this partnership came about.
St. Catherine Hospital is a European center of excellence for advanced diagnostics, orthopedic procedures and spine surgery, pain management, sport medicine as well as in the implementation of innovative diagnostics methods and personalized treatment strategies. In addition, St. Catherine is the official medical institution of the Croatian Olympic Committee and of the Croatian Football Federation. Therefore, many of the top-level athletes from variety of sports have been either diagnosed or treated at the hospital, including: Garry Kasparov (former World Chess Champion), Marin Čilić (Winner of the US Open 2014), Aleksandr Viktorovich Khoroshilov (the first Russian male to win a World Cup race (Schladming, 2015) since 1981) Gordan Giriček (NBA player: Memphis Grizzlies, Orlando Magic, Utal Jazz), Bojan Bogdanović (NBA player: Brooklyn Nets), Ivica Kostelić (former World Cup alpine ski racer and two-time Olympic gold medalist), Janica Kostelić (former World Cup alpine ski racer and four-time Olympic gold medalist), Blanka Vlašić (a high jump indoor World Champion), Niko Kranjčar (football player: Queens Park Rangers and Croatian National Soccer Team), Maria Clara Salgado Rufino (member of Brazilian Volleyball Team), Mathieu Carle (Canadian Ice Hockey player), Ivano Balić (one of the best handball players of all time.), Mirko Filipović (K-1 champion).Last but certainly not least, many football players have been either diagnosed or treated in our hospital as well, out of which some include: Burak Yilmaz (Beijing Guoan, China and The Turkey National Football Team), Mario Mandžukić (Juventus, Italy and The Croatian National Football Team), Luka Modrić (Real Madrid, Spain and The Croatian National Football Team), Ivan Rakitić (Barcelona, Spain and The Croatian National Football Team), Ivica Olić (Wolfsburg, Germany and The Croatian National Football Team), Mateo Kovačić (Real Madrid, Spain and The Croatian National Football Team), Šime Vrsaljko (Atletico Madrid, Spain and The Croatian National Football Team), Stipe Pletikosa (Real Club Deportivo de La Coruña, and The Croatian National Football Team), Niko Kranjčar (Glasgow Rengers and The Croatian National Football Team), Andrej Kramarić (Hoffenheim 1899, Germany and The Croatian National Football Team), Dejan Lovren (Liverpool, England and The Croatian National Football Team), Alen Halilović (HSV and The Croatian National Football Team), Ibanez Luis Ezequiel (Trabzonspor, Turkey), Josip Pivarić (DInamo, Zagreb, Croatia and The Croatian National Football Team), Tin Jedvaj (Bayer 04 Leverkusen, Germany and The Croatian National Football Team), Marko Pjaca (Juventus, Italy and The Croatian National Football Team, Nikola Kalinić (Fiorentina, Italy and The Croatian National Football Team), Marcelo Brzović (Internacionale Milano, Italy and The Croatian National Football Team), Domagoj Vida (FC Dinamo Kyiv, Ukraine, and The Croatian National Football Team), and dozens of others.
OneOme® RightMed test was co-developed with Mayo Clinic, with whom International Society for Applied Biological Sciences that I am in charge of and St.Catherine Hospital has had a long-standing relationship. St-Catherine Hospital is pioneering the implementation of the personalised medicine concept in clinical practice and our Center for Individualised and Preventative Medicine is designed to bring the latest and greatest innovations in translational medicine to our patients, from glycomics to pharmacogenomics and beyond. Pharmacogenomic testing is a critical addition to our program, as we know that we can optimize health outcomes for our patients by tailoring their medications to their unique genetic makeup. Our collaboration with OneOme resulted with the introduction of the OneOme® RightMed test in Europe and you are completely right, we will be expanding shortly to several EU member states.
10. And finally, for readers who are interested to take the RightMed pharmacogenetic test, what are the next steps, and where can they take it in Europe currently?
Currently, your readers can take OneOme® RightMed test at the St. Catherine’s Hospital in Zagreb. However, OneOme, co-founded by Mayo Clinic and exclusively licensed from Mayo Clinic, is working to deliver the most comprehensive, cost-effective pharmacogenomic testing and tools for all providers across the globe to use in everyday patient care. St. Catherine’s is partnering with OneOme fulfilling that mission.
(Paul Owen, CEO of OneOme, at the Zagreb press conference)
11. Two successful companies on a unique mission: the introduction of a personalised medicine concept to clinical practice worldwide. A difficult and challenging task?
OneOme and St. Catherine are creating effective strategic partnership based on performance excellence, innovation and visionary leadership in health care. OneOme is the company with incredibly professional and dedicated people. OneOme was named one of the World’s 50 most innovative companies for 2018 by Fast Company. St. Catherine Hospital is a teaching hospital of 4 universities and the official hospital of the Croatian Olympic Committee and of the Croatian Football Federation. The Hospital is a member of the prestigious The Leading Hospitals of The World family and a first European recipient of U.S. Global Healthcare Accreditation. In addition, St. Catherine Hospital is recipient of many national and international awards including “Croatia Super-brands 2016/2017 Award”, “National Champion for Republic of Croatia in The European Business Awards”, “Ruban d’Honneur Award for Customer Focus” and by overall rating is listed among the top 10 European Companies in its category during 2016. We strongly believe that our reputation, values, dedication and vision are essential to make our mission success.
12. OneOme and St. Catherine’s relationship seems to be very unique: a brilliant model of translational medicine concept with the goal of implementing recent scientific findings in a clinical practice.
You are right: This is not a vendor-client relationship; OneOme and St-Catherine are true partners in this program. There is a mutual commitment on both sides to make a positive impact on St-Catherine Hospital’s patients, first and foremost. We intend to continue working closely with OneOme to bring about enhancements to the platform and truly fulfill the promise of pharmacogenomics. Finally, OneOme and St. Catherine’s will present the results of collaboration during the “11th ISABS Conference on Forensic and. Anthropologic Genetics and Mayo Clinic Lectures in Individualized Medicine” to be held on June 17-22, 2019 in Split. More than 650 participants with 60 invited speakers (including 4 Nobel prize laureates) all together from 50 different countries will learn more about our collaboration as well as about our unique approach of implementing the concept of personalized medicine in clinical practice.
To learn more about the OneOme RightMed test, visit the St Catherine Specialty Hospital website.
