In early 2019, the UK National Health Service (NHS) launched a 10-year “Long Term Plan” aimed at improving the quality of patient care and health outcomes. As part of that plan, the NHS recognized cardiovascular disease (CVD), which affects 7.6 million people in the United Kingdom and is responsible for 27% of all deaths, as the single biggest health concern, where better prevention and disease management could save up to 150,000 lives over the next 10 years.
The link between high LDL cholesterol and CVD is well known. Over the years, multiple therapies have been developed to help lower excessive cholesterol levels. But despite the widespread usage and availability of standard drugs, especially statins, high cholesterol remains insufficiently controlled in some patients.
In January 2020, Novartis, NHS England, and NHS Improvement signed a first-of-its kind “population access” agreement. The agreement set forth a collaboration to proactively identify patients who have already experienced one heart attack or stroke and are at risk of a second due to their insufficiently controlled cholesterol levels, and to intervene by treating them with Novartis’s PCSK9 inhibitor, Leqvio (inclisiran). The agreement became a commercial deal in September 2021 following the positive recommendation by the UK National Institute for Health and Care Excellence (NICE) for Leqvio, which had been approved in the UK in January 2021 for adults with primary hypercholesteromemia or mixed dyslipidemia. The drug can be used alongside statins or other lipid-lowering drugs and will be offered to patients identified as high risk through their primary care physicians. Over the next three years, about 300,000 UK patients are expected to be treated with Leqvio.
The injectable drug is the first to use RNA interference to augment the liver’s ability to remove harmful cholesterol from the blood. Phase 3 clinical trials showed Leqvio could lower cholesterol levels up to 50% when given alone. When combined with statins, experts predict such a therapy could achieve a 75-80% reduction in cholesterol levels. It has also shown its ability to reduce LDL levels even when other treatments have failed. Clinical studies are continuing to determine the drug’s effects on CVD outcomes, with key data readouts expected in 2026. The NHS and Novartis are also conducting a large-scale primary prevention trial to explore the ability of Leqvio to avert a primary heart attack or stroke in patients at high risk. While two other PCSK9 inhibitors are available in United Kingdom – Amgen’s Repatha and Sanofi/Regeneron’s Praluent – Leqvio offers the advantage of twice-yearly dosing versus bi-weekly or monthly for the other products.
Despite NICE’s endorsement of the collaboration between NHS and Novartis, both the British Medical Association and the Royal College of General Practitioners have warned of serious concerns regarding the planned rollout of the drug in general medical practice. They cite the lack of long-term data on CVD outcomes and safety, given the possible side effects of treatment. They also note concerns about a lack of resources to support the additional workload that general practitioners, who are already stretched to their limits due to COVID, would bear for identifying, treating and monitoring patients who are prescribed the new drug. A usage trial is now underway in the Greater Manchester Health System to assess the feasibility of delivering Leqvio in primary medical practices, with results expected during 2022.
Novartis is now exploring a similar targeted population approach for Leqvio in the U.S. market, where the drug is expected to gain FDA approval in 2022. The company plans to approach 200 hospital systems that, using their own criteria and methods for identification, would pinpoint those heart patients who struggle to control their LDL cholesterol with existing drugs. The hospitals would then be able to offer Leqvio to identified patients in an effort to prevent further health complications. Some health systems, such as Geisinger, already take such a population health management approach to improve the health of its patients while controlling costs.