The future of precision medicine part 1: challenges and opportunities


Daniel Lim

The future of precision medicine part 1: challenges and opportunities

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The healthcare industry and governments around the world are turning to precision medicine as an opportunity and a potential saviour. Daniel Lim of Kirkland & Ellis discusses the issues around translating the promise of precision medicine into real world clinical practice.

The promise of precision medicine has been extolled by researchers and clinicians for some time, but as sequencing costs continue to fall, sophistication of data analysis and patient stratification increases and data science and artificial intelligence (AI) begin to partner with the life sciences industry in earnest, that promise now seems closer than ever to realisation. 

The prospect of individualised, truly science-based treatments backed up by a deeper understanding of the particular genetic, social and microbiological identity and environmental circumstances of the patient and/or their disease is simply too exciting to ignore.

Consumers have also embraced the genetic revolution, with direct-to-consumer genetic ancestry test kits reaching unprecedented levels of popularity over the last year, even to the point of becoming some of the top-selling products in the Black Friday and Christmas sales period in the US. 

According to MIT Tech Review, more people took genetic ancestry tests last year than in all previous years combined. The number of people who had their DNA analysed via direct-to-consumer kits more than doubled in 2017, now exceeding 12 million. 

Consumer genetics company 23andMe has recently received approval for its direct-to-consumer “ancestry and health” test to report on three mutations in the BRCA1 and BRCA2 genes associated with breast cancer.

In the context of spiralling healthcare costs, chronic underfunding and lack of access to health services, an increasingly aged global (and particularly first world) population, and the continuing rise of lifestyle-related disease, the healthcare industry and governments around the world are turning to precision medicine as an opportunity and a potential saviour.

This is the first in a series of articles intended to be a wide-ranging discussion of the opportunities and challenges that clinical and research communities, and the public at large, will face in translating the promise of precision medicine into real world clinical practice and improved outcomes for patients. 

The discussion draws on a wide range of sources and views, and in particular incorporates and comments on insights from recent expert forums on the topic, which include a Westminster Health Forum (WHF) keynote seminar and a panel session at the World Economic Forum (WEF).

This first article will provide an overview of some of the high-profile precision medicine initiatives being spearheaded in the US and the UK, briefly recap developments in 2017 and offer a snapshot of the capabilities and limitations of precision medicine.

Later instalments in the series will focus on particular technologies, and the opportunities or challenges that will need to be addressed by the field at a global and/or local level, including:

  • The interrelationship between data science and precision medicine, and the issues posed by big data in healthcare;
  • The challenge of translating precision medicine from research to clinical practice;
  • Creating the right regulatory environment to safely facilitate development of and access to precision medicine; and
  • The need to engage with the public as advocates for, active participants in, and the ultimate beneficiaries of precision medicine.

Initiatives on either side of the Atlantic

Public and private investment in precision medicine and population sequencing initiatives is on the rise around the world. With long and storied histories in the science of genetics and sequencing, the US and UK are among the countries seeking to lead the way in the field.

In the UK, precision medicine-based initiatives are a key plank in the government’s bid to reassure voters and the scientific community of the UK’s continuing commitment to scientific endeavour and position in the vanguard of the precision medicine revolution. 

The cornerstone of the UK’s push to be a world leader in the field is the publicly-backed 100,000 Genomes Project, run by Genomics England, which aims to perform whole genome sequencing (WGS) of the genomes of 100,000 eligible NHS patients with certain rare diseases or cancer

The well-established UK Biobank represents a rich and detailed source of human health data that is also now beginning to be mined for sequence information.

A collaboration of major pharmaceutical and biotech companies led by Regeneron and GSK has committed to the exome sequencing of all 500,000 UK Biobank participants by 2019 and, in April 2018, the UK Biobank announced a £30 million grant from the Medical Research Council for WGS of an initial group of 50,000 UK Biobank participants, with the ultimate goal of WGS of the entire cohort.

In the US, the Obama administration announced the creation of a “Precision Medicine Initiative” to much fanfare in January 2015—the key element of that initiative is now known as the “All of Us” Research Program

The All of Us programme aims to collect healthcare data (including medical history, lifestyle information, biological samples, physical measurements and genetic sequencing) from one million or more diverse participants around the US, with a focus on oversampling of communities that have traditionally been underrepresented in research. Following a pilot programme, open national enrolment for the programme began on May 6, 2018. 

In addition, there are multiple privately-backed population sequencing efforts working in parallel to generate large bodies of genetic data (not unlike the race to sequence the first genome between the public Human Genome Project and Craig Venter’s private Celera effort). Notable among these are Regeneron’s Regeneron Genetics Center and Human Longevity (a new genetics company founded by Venter).

A bumper year for precision medicine

If the past year is anything to go by, the pace of developments in the precision medicine field seems to be increasing rapidly. In 2017 there were a host of landmark developments in the field of precision medicine.  Some of the most significant are listed below, along with further recent developments on each front.

  • The Food and Drug Administration’s approval of the first chimeric antigen receptor T-cell (CAR-T) therapies (Novartis’s Kymriah and Gilead/Kite’s Yescarta). Kymriah has just recently been granted approval for its second indication in relapsed/refractory large B-cell lymphoma, and both Kymriah and Yescarta are on the verge of approval in Europe.
  • The first approval of a medicine by reference to the genetic features of the cancer as opposed to its site of origin (Keytruda). In this same vein, Loxo Therapeutics, a company specialising in the development of such targeted tumour agnostic treatments, has just released an abstract ahead of ASCO 2018, reporting a 69% overall response rate in its phase I trial of LOXO-292 in 32 RET-fusion positive patients (including those with non-small cell lung cancer and papillary thyroid cancer), a result seen by many as the most impressive among those due to be announced at the leading oncology conference.
  • The first in-human precision gene-editing trial (using zinc finger nucleases—Sangamo Therapeutics’ treatment for Hunter Syndrome). CRISPR-based approaches are not far behind in the clinic, with CRISPR Therapeutics’ Clinical Trial Application in Europe for a phase I/II of its lead pipeline product CTX001 for β‑thalassemia approved in Q1 2018 and due to start in the second half of 2018.
  • The continued refinement and evolution of CRISPR-based gene-editing techniques (eg, base editors, epigenetic expression modulators). A new member of the RNA cleaving Cas13 class (Cas13d) has recently been characterised by two sets of researchers and there is speculation it will offer advantages over previously identified members of the class.
  • The achievement of the first continuous DNA sequencing read over one million bases in length, using Oxford Nanopore’s MinION nanopore sequencing platform. Efforts in 2018 have smashed previous records, with the first continuous sequencing of over two million bases recently reported by researchers at the University of Nottingham.
  • The 100,000 Genomes Project nearing the halfway mark in terms of genomes sequenced (41,582 as at December 4, 2017). As at May 4, 2018 the number of genomes sequenced stands at 60,679.
  • The release of the Initial Protocol for the US National Institutes of Health All of Us Research Program. On May 6, 2018 the programme officially opened national enrolment and on May 23 the National Institutes of Health made a funding announcement for Genome Centers to generate genotype and whole genome sequence data from participants’ biosamples. Applicants may request funds to generate and analyse genotype data from 100,000 participants in the first year, rising to as many as 200,000 participants in the following years of the five-year programme.

Against this backdrop of rapid progress, the public and private sectors seem to be in increasing agreement that we are on the cusp of a dramatic change in the way we look at and deal with human health—one that comes with huge potential benefits, but also with serious challenges to established clinical, regulatory, educational and societal paradigms and practices. 

Without early engagement with stakeholders at all levels, and collective action to identify and address those challenges, we run the risk of precision medicine increasing inequality, failing to realise its potential, or in some circumstances even achieving worse outcomes for the vulnerable in society.

Understanding capabilities and limitations

Many clinicians see personalised, precision medicine as the fulfilment of something of a philosophical medical goal, ie, that ideally all medicine should be personalised and treatments should be designed and prescribed in a bespoke manner for a particular patient, taking into account the precise nature of their disease and the unique environmental, genotypic and phenotypic characteristics of the patient.

While this has been the ideal, it is only now that we are in a position to really begin to realise it. The recent advances in precision medicine are being fuelled by a confluence of dramatic advances in a number of related technologies/fields of study including data science, AI, genetic sequencing, molecular diagnostics, biomarker identification, targeted treatments and the development of large electronic databases of patient information.

Although the term is often used in a broad and inclusive sense to cover a range of more targeted and personalised approaches to medicine (often with a genetic component), to give a more concrete idea of the vast potential of the field it is helpful to expressly set out some of the specific developments that fall under the umbrella term of precision medicine:

  • More targeted drug discovery and development processes (eg, employing AI and existing datasets to perform better in silico target identification);
  • Better identification of highly responding subpopulations of specific indications (whether genetically linked or otherwise) and use of that information in the design of clinical trials and ultimately approved treatments;
  • The prescription of treatments adapted specifically to the physical (eg, body weight, and smoking or alcohol habits), genetic, environmental and disease characteristics of the particular patient—not only in terms of what treatment should be administered, but also the particular dose and regime for administration;
  • The identification of genetic or biological markers better correlated with disease and/or the likely efficacy of specific treatments, and the development of robustly validated companion diagnostics to screen for those markers;
  • Better analysis of clinical datasets and real world evidence to provide a more reliable indication of the efficacy and safety of new treatments (and adaptation of regulatory processes to recognise new evidentiary standards); and
  • The development of high quality (and economically viable) screening protocols to identify high-risk individuals and enable prevention of disease rather than simply reactive treatment.

Fully realised, precision medicine would yield huge benefits in terms of clinical outcomes for individual patients as well as more broadly within society, and for heavily strained healthcare systems around the world. 

For patients in particular, it would mean a treatment regime specifically tailored to have the highest chance of success and lowest risk of adverse effects for that particular patient. 

This is in stark contrast to the current paradigm in which, as Sir Munir Pirmohamed, NHS chair of pharmacogenetics, noted at the WHF, 90% of drugs currently being prescribed work in only 30 to 50% of the population. 

As such, the 50 to 70% of people who are being administered a drug that will not work for them are being unnecessarily exposed to the risk of adverse events, which account for 6% of all admissions to hospitals in the UK—equating to 8,000 beds and a cost of £1 billion to the NHS. 

A personalised precision medicine approach would therefore result in a dual benefit: to the patient, by improving efficacy outcomes and reducing adverse effects; and to healthcare systems, by reducing expenditure on ineffective drugs as well as the cost of treating the adverse effects of treatments.

However, precision medicine is not a magic bullet, nor is it a socially and economically neutral endeavour that is immune to the influence of bias in its many forms (including cultural, socioeconomic, geographic and genetic). 

Precision medicine will depend on the formation of appropriate organisational and regulatory infrastructure to control for such biases and create the necessary environment for precision medicine to come to fruition.

From a practical perspective, the “precision” of precision medicine relies on the availability of large amounts of high quality, diverse data to accurately and equitably inform diagnosis and treatment approaches. The quality of the outcomes facilitated by precision medicine will be determined and limited by the quality of the data used to inform them.

These issues will be discussed in greater detail in the later instalments of this series, starting first with the topic of data and precision medicine—what data is needed, how is it used, what should it look like and what concerns does this raise for patients and society?

Daniel Lim is a partner at Kirkland & Ellis. He can be contacted at: 

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