Inside the technological, legislative and financial checks on the rise of genome-based medicine

In order to meet the social and patient needs of the twenty-first century, current drug development will need to dramatically improve in efficiency. Genomics and AI present a real opportunity to revolutionalise R&D programmes, especially at the earliest stages of product development, in screening for potential drug targets and corresponding drug candidates to address diseases or conditions with a dire unmet medical need.

In July 2017, the UK Government’s chief medical officer, Dame Sally Davies, unveiled a plan to fully embrace a new era of genome-based personalised medicine. This has been heralded by many as welcome news. According to her annual report, the ‘genomic dream’ will provide millions of patients with the opportunity to have their DNA tested as genomic sequencing. The report also acknowledges that we are entering an age of precision medicine and says the NHS must act fast to keep its place at the forefront of global science.

Genomic medicine has huge implications for the understanding and treatment of as many as 7,000 rare diseases, cancer and infections. The highly successful 100,000 Genome Project has now sequenced more than 31,000 genomes from patients with cancer and rare diseases. In this era of advanced therapies, genomics will open up avenues to develop new therapeutic approaches based on genes, cells, tissue engineering, iRNA and, most recently, gene editing technologies to target genomic location to repair genetic aberrations.

However, the true potential for broader application of genomic analytics lies in the opportunity to optimise care and management of patients, with healthcare delivery that is focused on planning the patient journey, rebalancing the need for disease prevention and earlier diagnosis, as well as maintaining individual wellness. These public health imperatives underlie the call for greater investment and R&D for precision medicine.

There is increasingly a shift in treatment paradigms away from the one-size-fits-all approach, and a generally adopted view that customised treatments are promising. Whole genome sequencing is not routinely applied for every cancer patient for cost reasons. However, it is recognised by many that profiling tumour DNA assists in prioritising anti-cancer treatment, by identifying specific therapies to which a patient’s cancer may be sensitive or resistant.

But whilst the logic behind the search for mutations may seem simple, the technology is not. Sophisticated computational algorithms are needed to determine whether the DNA of a malignant tumour is a true mutation or a normal variant. Moreover, gene sequencing provides only one part of the overall picture; a complete picture of the biological environment is needed to properly understand the tumour’s behaviour. AI systems like PhysiScore are capable of analysing real-time data alongside other physiological and anatomical inputs, and may facilitate earlier diagnosis of an individual’s susceptibility to develop a particular condition.

Regulatory authorities on both sides of the Atlantic have developed new pathways and policies to facilitate the earlier adoption of such new technologies for patients to access, and to stimulate R&D. These include break-through designation and, most recently, the 21st Century Cures Act in the US. Various published communications by both the EMA and the FDA show they think it’s in the interest of public health to do so.

The new US law speeds up various innovation pathways and creates an opportunity for the FDA to apply recent advances in technology and analytics and scientific and evidentiary models to continue evolving regulatory programmes. The regulatory approaches adopted by the EU largely leverage the existing enabling regulatory framework to enable adaptive licensing to facilitate market access. In response to convergent technology to develop drug/device combinations to optimise patient care, the regulatory regime for general medical devices and in vitro diagnostic medical device has also been overhauled in the EU.

But despite these scientific and regulatory endeavours, payers and policymakers are increasingly struggling with rising healthcare costs. These are due to significant shifts in demographics, and the surge in the transformative medicines and medical technologies which have introduced in the recent years. Cost-containment measures have resulted in many innovative therapies, including advanced therapies, approved centrally in the EU not being adopted for clinical applications. Standard approaches to diagnosis have been favoured, instead of more customised methods, because of the restrictive reimbursement pathways. The health technology appraisals underlying the decision to grant market access often result in a set menu of methods being made available for clinical applications. This effectively restricts a customised approach on cost and affordability grounds.

Many of the new technologies intended to treat small populations are not only costly to develop but, because they are intended for treating orphan or ultra-orphan conditions,  the costs of production are relatively high. Biological products including recombinant proteins (which now account for over 40 percent of all the new products currently in development) are susceptible to variability of the biological processes. In regulatory terms, manufacturing controls are generally stricter, to minimise attritions and product failure, and hence biological products are costly to produce. These considerations ought to be recognised by the  policy makers.

The debate on market access is particularly intense in the UK, where the healthcare budget has not kept pace with the speed at which new technologies are being developed. The cost of these technological advances has threatened to increase the strain on the national health system, which is required to achieve savings of £22 billion by 2020. The restraint experienced in the UK resonates similarly across Europe and, increasingly, in the US, which seemingly seeks to contain its annual healthcare spend, currently in excess of $3 trillion.

There is clearly a tension between the need for transformative innovation and timely access to innovation. Innovation cannot be viewed as inclusive if it is not adopted and diffused in the healthcare system for the benefit of society at large. Market access, which is often shaped by cost-effectiveness and affordability, may be the next innovation that is needed in order to ensure sustainability in healthcare delivery.

Market access not only benefits patients, but also the next generation of healthcare professionals, who need to acquire practical experience in using these new therapeutic approaches in order to ensure that an appropriate equilibrium is struck between basic research and future translational clinical research in the sector. Pharmaceutical and clinical practice ought to represent a dynamic professional endeavour, a positive response to present and future technological challenges.

Success in securing market access lies with the involvement and engagement of various stakeholders, most importantly the end users of the new technologies, namely the patients and the healthcare professionals. Patients have been acknowledged by many as being the centre of the healthcare system, and are well placed to assess the true value of new treatments in a defined patient journey.

Dr Lincoln Tsang is a partner in the global life sciences practice at international law firm Arnold & Porter Kaye Scholer. He also trained in cancer pharmacology and toxicology