Britain’s good idea for custom genetic medicines

RARE DISEASES are, individually, rare. Collectively, however, they are anything but. They affect perhaps 300m people around the world. Many are highly debilitating. Plenty cut young lives tragically short. Some 80% are caused by faulty genes. Breakthroughs in genomics (which let doctors find problem mutations) and genomic medicines (which edit mutated DNA or disrupt how it is turned into proteins) mean that more and more are treatable. Yet sufferers are seldom treated.

That is because drug firms have little incentive to develop custom medicines and get them past regulators. The process is costly and tedious for businesses which are set up to make drugs at scale. Probably fewer than 100 customised drugs for rare diseases have been made since 2018, usually paid for directly by desperate parents with money raised through charity.

It does not have to be this way. This month Britain’s Medicines and Healthcare products Regulatory Agency (MHRA) approved a novel sort of clinical trial. Ten children, each suffering from an ultra-rare genetic neurodegenerative disease that threatens his or her life, will each receive a unique version of a known drug molecule. If the trial is successful, the MHRA will give the nod not to each custom drug one by one, but to the process of making them. The firm doing the tailoring, EveryONE Medicines, would be able to make as many variants as there are children in Britain needing care and treatable with the underlying compound. America’s Food and Drug Administration is adopting a similar approach. The world’s other regulators should likewise follow Britain’s lead.

The watchdogs’ job is to limit the risk to patients while maximising clinical rewards. This risk-reward determination is relatively straightforward if firms conduct rigorous trials involving lots of patients and a placebo-taking control group. But regulators get nervous about custom treatments, especially for rare diseases with little or no prior clinical data behind them. The risks, in the regulators’ eyes, are hard to quantify; the outcomes, uncertain.

The MHRA’s innovation is to take seriously the trade-off between the unknown risk of customised treatment and the almost inevitable suffering in its absence. It may be that one day, tragically, a child dies after receiving a custom-made drug. That is not an argument against such treatments—unless a safer alternative exists.

The British approach should spur innovation, especially if adopted widely. EveryONE Medicines reckons that process approval could cut the cost of developing custom therapies from $2m-3m to below $1m and the time it takes from two or three years to less than nine months. As prices fall, demand will rise, including, eventually, from state-run health-care systems.

Combined with greater regulatory clarity, a signal from governments that they would pay for such treatments and, ideally, universal whole-genome sequencing of newborns (a large trial of which is also under way in Britain), would attract more biotechnology companies into the market. Already, one new biotech firm developing custom therapies based on gene-editing for other rare conditions has expressed interest in the MHRA’s process approval. The more countries emulate Britain, the faster this virtuous centrifuge will spin—and the more young lives will be saved. ■