Current realities and reasonable expectations for sustainable personalized medicine

PM Roadmap: what to tackle first?

For personalized medicine to advance, however, we must globally move forward in several directions. In its 2030 Vision, ICPerMed (International Consortium for Personalized Medicine) highlights four paths to cover: 1) data and technology, 2) cross-sector synergies, 3) healthcare reform and 4) education approaches. When virtual attendees to the panel were polled, the majority voted for healthcare reform (55%), followed by intersectorial synergies, data issues and educational approaches. For Amgen Iberia General Manager Fina Lladós, intersectorial collaboration is crucial, as personalized medicine has increased the need for a variety of experts and knowledge sources. Dr. Lladós ranked data recording and sharing, second and raising awareness of the importance of PM, third. “All of us, as a society, are future patients,” and if we understand how important PM is, we will push for better treatments more efficiently and, as a result, healthcare systems will get the reform they need.

Enriqueta Felip, head of the Thoracic Cancer Unit at Vall d'Hebron University Hospital, agrees with Dr. Lladós on the importance of intersectorial collaboration: boosting synergies among the various stakeholders is crucial in order to develop a successful personalized-medicine program. In her area of expertise, oncology, it involves high-quality molecular pre-screening, standard of care consultations and pharma companies developing drugs for patient subsets. Registries are crucial: even the FDA is open to the possibility of approving drugs for uncommon molecular alterations based on registries. “Increasing synergies is the first step in this adventure,” said Dr. Felip. 

We can’t forget about any of these four pillars (data issues, intersectorial synergies, healthcare reform and educational approach), since they sustain this transformation just like a table stands on its four legs. Toni Andreu, scientific director of EATRIS, agreed that these four pillars are the main challenges and opportunities for developing and adopting the global PM agenda, as they involve a complete reengineering of the system. “We have to reverse-engineer the process,” Andreu says. Science is providing great tools, by identifying targets and biomarkers for the right treatment at the right time, but we must tackle the agenda of the policymakers ultimately in charge of restructuring the healthcare systems. And this has to be done with the cooperation of all the stakeholders involved in the process: academia, industry and the patient community, to help policymakers dismiss the idea that personalized medicine is expensive and creates tension between individual and collective healthcare.

His colleague at EATRIS Edwin van de Ketterij, Clinical Director of the EATRIS-ERIC project, preferred to emphasize data and technology, and its spill-overs across all sectors. Let’s take electronic data records as an example. The electronic tools used by different hospitals in the same country vary widely. These systems are not standardized and data cannot be combined into larger sets. Ketterij urged everybody to support projects like IMI EHDEN (European Health Data and Evidence Network) to standardize electronic health records, biomarkers and multi-omics data in Europe. Hospitals can apply for grants to have their systems standardized. But Ketterij also referred to education as the great challenge. People currently working in healthcare will have to retrain and upskill in the use of new data and new systems. Education curricula will have to address this challenge now, because by 2030 when the ICPerMed vision should be a reality, it will be too late.

Is today’s medicine already personalized? Are industry, academia, policymaking and clinical research doing their best?

Current achievements

Amgen Iberia General Manager Fina Lladós says the company, as a leading biopharma firm, is contributing through their three main strengths: human genetics, molecular engineering and pathway biology. In 2012, US group Amgen started focusing on genetics and acquired the Icelandic gene hunter Decode to correlate genetics with diseases and validate therapies. Amgen has a broad toolkit of drug modalities to pioneer a new approach to drug discovery. This approach seeks to gain deep biological insights into disease before selecting the best tool to target them. Lladós also referred to Amgen currently using personalized medicine approaches with 25 molecules for oncology.

EATRIS also has a lot to say, as an organization that reflects the challenges and opportunities in translational medicine in Europe, from basic to clinical research. Created by the European Commission about 10 years ago, it represents the joint efforts of 13 European countries through a network of roughly 120 biomedical research institutes. As its Scientific Director states, the Spanish and Catalan communities are very active in EATRIS, with the Vall d’Hebron Research Institute leading the entire Spanish scientific community. For Toni Andreu, personalized medicine is a great landscape for cooperation. One of the best examples is EATRIS Plus, the flagship project on PM funded by the European Commission (in which Biocat is also a partner) that aims to develop novel tools to move beyond genomic medicine, because the complexity of human disease goes further than just genomic knowledge. The contribution of EATRIS Plus will be, among others, new tools for a multi-omic approach and a shared mindset to accelerate PM development and implementation.

As a medical oncologist working in a hospital in Barcelona, Enriqueta Felip’s department sees 5,000 new patients with cancer each year, more than 3,500 of which will need systemic therapy. In the past, patients were treated with surgery, biotherapy or chemotherapy, according to the location of their disease: lung, breast, colon, etc. But over the past decade, molecular markers have made a difference. For patients with cancer, precision medicine is a reality. For example, to know the risk for recurrence in patients with breast cancer, we need to search for correlation of some genomic alterations. In patients with colon cancer, we need to check the status of the RAS oncogene family, and with lung cancer patients, we test for EGFR (epidermal growth factor receptor) mutations and for ALK and ROS rearrangements before starting any treatment. Just as, in patients with melanoma, we also test for proto-oncogene BRAF mutations. 

Challenges

For a company like Amgen, unlocking PM potential might entail working with policymakers in three areas: 1) applying, modelling and simulating several clinical trials to accelerate development, 2) providing an example of how to adapt clinical trials to narrow populations, and 3) using real-world evidence to understand what is happening in clinical practice and thus inform future strategies. So, for the BioRegion of Catalonia to become a global reference in PM, all public and private stakeholders must work hand-in-hand within the ecosystem.

For hospitals, diversely, the challenge might be setting up teams with preclinical, translational and clinical experts to work together to advance from translational research towards precision medicine, like Dr. Felip’s team at VHIO. Also key is the role of core units in molecular pathology, genomics and proteomics, allowing for strong programs in clinical trials that help make PM more real. This, and the fact that the European health systems now probably better understand the importance of strategies in personalized treatments.

But for Edwin van de Ketterij, who started working in clinical trials over 20 years ago to help bring new and better treatments to patients, and more quickly, we’re closer to personalized medicine but not close enough. Or, at least, it depends on the disease in question. From his work in the EU-PEARL project (EU Patient-Centric Clinical Trial Platform) funded by the IMI and co-coordinated by EATRIS, he believes that Platform Clinical Trials are the answer. What makes them different from normal clinical trials? The answer is: common placebo and control arms but multiple compound arms in the same platform, coming from different pharma companies in a more collaborative setting than normal clinical trials. This allows for a personalized-medicine perspective in clinical research.

The rich insights provided by Fina, Toni, Enriqueta and Edwin in the 40-minute panel discussion was a gift for participants and attendees, which I particularly enjoyed as the session chair. To the question “Is PM failing to deliver the transformation promised?”, they provided complete and sustained arguments in favor of hope. I wish that this friend of mine, the one that usually takes a coffee break when this subject arises had attended this panel on current realities and reasonable expectations in this path towards sustainable personalized medicine.