Pharmacogenomics Research Could Save NHS at Least £41 Million Annually

An analysis of NHS prescriptions data has revealed the huge potential for pharmacogenomics to reduce ineffective prescribing and adverse effects, which could save millions of pounds for the NHS. The prescriptions data reveals that in 12 months (April 2021 – March 2022), NHS England spent more than £412m on common opioid and SSRI antidepressants. Yet, 1 in 10 people have a mutation on CYP2D6 gene, which means they metabolise and react to these drugs differently. Prescribing these drugs to people with CYP2D6 variation is costly and potentially harmful – with some people gaining no benefits from the drugs, and others at an increased risk of overdose. With such a high incidence of CYP2D6 variation in the UK population, using genetics to inform the prescribing of opioids and SSRIs could save at least £41 million each year.

“This analysis only examines one gene and two families of drugs. It’s a drop in the ocean for the wider benefits PGx research could bring to the total £9.69 billion spent annually on prescriptions in England, as well as the unimaginable improvements for patients of prescribing more personalized treatments,” comments Neil Ward, General Manager for PacBio EMEA. “PGx prescribing guidelines exist for several drugs on the market – with some drugs even requiring genetic testing before they can be prescribed – but there are still more genetic variants to discover. Now that whole genome sequencing technologies are faster, more affordable, and more accurate than ever, it’s time the UK invested in PGx research, so we can better understand the connections between certain gene expressions and therapeutic response.”

Pharmacogenomics (PGx) research analyses individuals’ genetic makeup to determine how they may respond to a certain medicine. In the case of the CYP2D6 gene, 8% of the population lack the enzyme that reacts with opioids and SSRIs entirely, meaning they cannot metabolize these drugs, so they have little to no effect for those patients. Further, an even bigger fraction have some of the enzyme present, but have a reduced activity score, meaning these patients are slow metabolizers. In contrast, 2% have more than two copies of the gene, which causes ultra-fast metabolism of these drugs. This means that after administration of a medication, it reaches the bloodstream faster and at a higher concentration, putting these patients at a greater risk of overdose. Recent studies by the U-PGx Consortium have proved that altering dosage according to someone’s genome could reduce adverse drug reactions by 30% – which currently contribute to 6.5% of hospital admissions.

However, identifying genetic variations that are linked to drug response is a complex process, requiring highly accurate, in-depth sequencing of someone’s genetic makeup. While some variation is straightforward to capture using technologies such as short-read genetic sequencing, certain genes are too complex or far apart to be captured by short-read alone. Therefore, an accurate, complete picture of a person’s genome is required to ensure that rare or novel variations, which might change how people respond to drugs, are not missed.

“Thanks to recent advances in highly accurate genomic sequencing technologies, the potential of PGx is closer to being realised, and we are about to embark on the next phase of PGx research,” adds Neil Ward. “It’s exciting that we’re already starting to see this reflected in the NHS’s Genomic Medicine Strategy, which commits to incorporating PGx into the service as a standard. The UK now needs to solidify its place as a leader in the field.”

Methodology

The analysis examined the NHS Prescription cost analysis 21/22, looking for drugs affected by CYP2D6 according to the Clinical Pharmacogenomics Implementation Consortium. The total cost of these drugs was summed to get a total of £412m. The savings cost of £41 million was calculated as 10% of the total, based on the knowledge that 8% of the population are slow metabolizers, and 2% were ultra-fast metabolizers.

Opioids impacted by CYP2D6:

• alfentanil
• buprenorphine
• codeine
• fentanyl
• hydrocodone
• hydromorphone
• levomethadone
• methadone
• morphine
• naltrexone
• oxycodone
• remifentanil
• sufentanil
• tramadol

Cost to NHS of these drugs in FY 21/22: £326,298,385.91

SSRIs impacted by CYP2D6:

• citalopram
• escitalopram
• fluvoxamine
• paroxetine
• sertraline

Cost to NHS of these drugs in FY 21/22: £86,134,329.23

Combined total= £412,432,715.14 (412 million)