Breaking the code - companion diagnostics
Companion diagnostics are transforming modern medicine by using each patient’s genomic information to guide treatment decisions. The benefits become clear in the cancer clinic at the Queen Elizabeth Hospital Birmingham, England.
Visitors to Queen Elizabeth Hospital in Birmingham, England, have a unique opportunity to walk through a historic location known for advances in medicine, and at the same time experience a place where modern medical breakthroughs are being made. The first buildings were built in the 1930s and opened by King George VI and Queen Elizabeth, who was the namesake of the original and new hospitals and would later go on to become the Queen Mother. The new Queen Elizabeth Hospital Birmingham (QEHB) opened in 2012 with a commitment to excellence in medicine.
Many of the innovations shaping the daily treatment of patients in Birmingham have their origins about 90 miles away on the outskirts of Manchester, located next to the city’s university complex. In a traditional red-brick building that forms a striking contrast to the glossy, high-tech face of QEHB, a rapidly growing team of more than 150 QIAGEN employees work on the development of new companion diagnostics slated to guide treatments with novel drug compounds that will sooner or later find their way into medical practice in Birmingham and elsewhere.
In one of the conference rooms, a group of QIAGEN managers from around the world gather to discuss the progress of ongoing projects. Leading the meeting is Vincent Fert, a French scientist and entrepreneur who is now a senior executive leading QIAGEN’s initiatives in Personalized Healthcare. He was a founder of Ipsogen, a global leader in diagnostics for blood cancers that became part of QIAGEN in 2011.
“QIAGEN has demonstrated that we have the right technologies and can develop, obtain regulatory approvals, achieve strong reimbursement levels and also commercialize assays that are bringing the power of Personalized Healthcare to patients and healthcare systems around the world. Our commitment to innovation means that patients and physicians are getting guidance for crucial medical decisions from the precise, reliable information provided by the therascreen portfolio of companion diagnostics,” Fert says.
The 2012 FDA approval of QIAGEN’s therascreen KRAS test kit on the Rotor-Gene Q MDx and its subsequent U.S. launch marked not only a significant milestone for QIAGEN’s business, but also for Personalized Healthcare in general. Only a few months later, approximately 50 % of the corresponding testing volume in the U.S. had converted from “laboratory-developed tests” to QIAGEN’s FDA-approved companion diagnostic. And the KRAS launch has provided a model for QIAGEN’s co-development and regulatory submission of other novel drug-diagnostic combinations.
Dr. Philippe Taniere, Consultant Histopathologist, QEHB
“With the U.S. launch of our KRAS companion diagnostic, QIAGEN has achieved a major milestone on the promise in Personalized Healthcare,” says Fert. “QIAGEN’s team carved out the path to FDA approval for a standardized, highly reliable test paired with an important drug from our pharma industry partner for metastatic colorectal cancer. We took a proactive approach to securing reimbursement from payers based on the value of our companion diagnostic and won market acceptance with rapid conversion to the FDA-approved test.”
Asked about the key to QIAGEN’s progress in Personalized Healthcare, Fert says, “We’re successful because we have two sets of customers – the pharmaceutical industry, which needs to target its drugs to succeed, and the diagnostic labs that serve healthcare providers – and our business model and capabilities allow us to meet the needs of both of them. We can translate the needs of one world into the requirements of the other world.”
QIAGEN brings special skills to co-development programs with pharmaceutical R&D. "Cancer is very fragmented,” explains Dr. Stephen Little, a pioneer in companion diagnostics and now a senior advisor to QIAGEN on Personalized Healthcare. For every oncology drug in development, researchers investigate various potential diagnostics. Then, he says, the researchers choose the biomarker that will be used to select suitable patients for the drug, and that is where QIAGEN comes in. “Our role is to develop a diagnostic test which will allow reliable measurement of the biomarker in clinical samples to allow the selection of patients most likely to benefit from the therapy.”
Current programs at QIAGEN address therapeutic areas that include cancer, autoimmune conditions, and Central Nervous System disorders, involving many new drugs in clinical development.
Asked about the future, Dr. Ravetto says, “We know there’s going to be a desire to have multiple tests for a single patient – so you do a KRAS test, you might do an EGFR test and then there are other less prevalent mutations, which are all related. You’ll be able to do a panel of tests – but they all will be able to develop a picture as to what the best therapy is for the patient.”
Mr. Watts sees the future of companion diagnostics evolving further: “Infectious disease has in fact led the space of companion diagnostic test development, through HIV testing, through other areas as well – but today it’s predominantly oncology. We’re now moving into more complex diseases such as autoimmune diseases and rheumatoid arthritis, other rheumatology-based diseases, and we’re also expanding into more complex diseases such as Alzheimer’s and Parkinson’s.”
Dr. Neil Steven, Oncologist, QEHB
Dr. Taniere heads the University Hospitals Birmingham NHS Foundation Trust’s molecular pathology service integrated in the histopathology department, which is based in the Trust’s QEHB and breaks the code of cancer on a daily basis. The dynamic Frenchman has been in Britain for many years building the formidable molecular pathology unit. The whole team has 30 scientists, technicians, laboratory assistants in the labs and 10 secretaries, who deal with about 30,000 cases a year.
“We look into the cells – we extract DNA or even RNA and we look at very specific alterations in genes or levels of expression of genes,” Dr. Taniere says. Where companies like QIAGEN have been “extremely helpful and supportive, they’ve provided us with kits and equipment, which have been set up to work in what we have in routine practice – in terms of solutions allowing us to process tumor samples and kits targeting the specific alterations which we need.”
Since 2009, his team has done over 100 KRAS tests every month for colorectal cancer patients from the area, from many other hospitals in England and some referrals from abroad. BRAF is a gene that is tested in melanomas, so Dr. Taniere also processes more than 100 BRAF tests a month. “We also test 200 lung cancers for EGFR mutation. So in sum it has already become a big volume of tests that have to be processed, which is very exciting,” he says.
Adoption of companion diagnostics “is extremely vital and millions are invested. When it comes to diagnostics, it has to be fully validated, it has to be,” Dr. Taniere explains. Along with growing demand for molecular tests, this prompts many laboratories in this area to shift their entire workflows to automated solutions such as QIAGEN’s QIAsymphony RGQ, which not only help to cope with rising test volumes but also ensure a higher comparability of results and minimize the risk of sample mix-ups.
500 tests for the KRAS, EGFR and BRAF biomarkers a year show the need for laboratory automation
Accordingly, all kits Dr. Taniere and his team use for the diagnosis need to have official validation such as the CE-Mark in Europe or FDA approval in the U.S. He sees the future as technology-driven and constantly evolving, while keeping with accepted standards – a widespread view that is reflected in QIAGEN’s efforts to further expand the menu of validated tests in Personalized Healthcare and other application areas.
Asked if he believes next-generation sequencing or multiplex testing will become the only way of the future, he replies, “I don’t believe one technique will replace everything – we need to cover all the patients, every type of tumor, every alteration – which makes it more exciting. But we need to have some companies with these wide panels of kits and techniques working and upgraded to follow the needs.”
Additionally, the challenge is to translate the vast amount of molecular information into actionable clinical decisions. “The KRAS test – for example – helps us to identify patients that will benefit from novel targeted treatments. But what do we do with the others?” Dr. Taniere states simply, “We don’t have three other drugs – so currently they go back to classical chemo which is not selective.” The issue is extremely complex. Dr. Taniere concludes with a question, “So with next-generation sequencing, I can test any tumor for everything I can possibly imagine. But what do you do, if the data is not validated and if you don’t have the treatment?”
Upstairs is the cancer clinic, which is also run by Dr. Steven. The ward is a circular room with the nursing center in the middle, hospital beds lining the walls and comfy couches well-placed for the visitors returning for follow-up checks. The patients are good-natured and the atmosphere is homelike as the nursing staff is sunny, sympathetic and compassionate. The nurses talk quietly to those being seen to, and sometimes the brightly-colored curtains are drawn close around the beds. But mostly those visiting rest on the large leather chairs.
One of the patients is Allan Robbins, name changed to protect his privacy, suffering from rectal cancer and on the sixth day following surgery. Looking pale yet quietly confident, the older man is resting in his room in the ward, lying on his side and valiantly drinking a cooling cup of tea with a straw.
“I had symptoms and thought ‘It’s just hemorrhoids’ but eventually went to have it checked out,” he admits wryly. “In early June the GP checked me over and the week after that I was here. I had a series of scans, MRI and CT scans and biopsies to decide what the problem was and was referred to the oncologist who put me on a chemo- and radiotherapy course for five weeks. There was then quite a big gap and I recovered from it. I was going out and driving.” His process also included being tested for KRAS to help guide treatment options.
Asked what would make his life easier, Mr. Robbins thinks and replies, “If I had one person in charge of me, that would be nice.” With cancer treatment already heading toward use of multiplex testing and next-generation sequencing, the way of the future could well be to equip each patient’s physician with all of the information needed to evaluate options and select the best possible treatment.
Doctors are beginning to be in position to predict the outcome of treatments, Dr. Steven says. “Essentially we use a predictive marker – if people have KRAS mutations, we do not use these antibodies. If they are not KRAS mutated, then it becomes feasible to use them.” He continues, “It’s built into our clinical algorithms – it’s also built into our funding algorithms – we would not be permitted funding for using these expensive drugs if that’s mutated. Both our reimbursement system and our clinical decisionmaking are critically dependent on what goes on in our pathology department.”
Dr. Steven adds, “As we move forward with targeted treatments, then having this kind of molecular diagnostics becomes very important, both in terms of personalized medicine for patients and in terms of the way the funding works. It’s obvious to us all that we can’t afford everything under all circumstances, so stratifying medicine becomes increasingly important to healthcare and to our patients.”