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Two new drugs to tackle antibiotic resistance

Medicines regulator National Institute for Health and Care Excellence (NICE) has announced two new antimicrobial drugs – cefiderocol and ceftazidime–avibactam – are close to becoming the first made available as part of the UK’s innovative subscription-style payment model.

NICE today published draft guidance estimating their value to the NHS.

The NICE evaluations of cefiderocol and ceftazidime–avibactam form part of a project with NHS England and NHS Improvement and the Department of Health and Social Care (DHSC) that aims to incentivise research into and development of antimicrobials by testing innovative approaches to evaluating and paying for them.

The drugs will only be used to treat patients with severe drug-resistant infections who would otherwise have limited or no other treatment options.

NICE says that the new subscription-style payment model has been designed to try and address the lack of new antimicrobials being developed and the growing threat posed by antimicrobial resistance. In 2020, only 41 new antimicrobials were being evaluated in clinical trials compared with about 1,800 immuno-oncology drugs.

The NICE draft guidance on cefiderocol and ceftazidime–avibactam provides an estimate of their benefits to the health of the overall population in England measured in quality-adjusted life years (QALYs).

What is Antibiotic Resistance?

Antimicrobial resistance develops when the pathogens that cause infection evolve to make antibiotics and other antimicrobial drugs less effective or stop them from working altogether. It’s a serious global problem and the World Health Organization has highlighted it as one of the 13 urgent health challenges of this decade. In January 2019, the UK Government published its vision for antimicrobial resistance to be contained and controlled by 2040 and its five-year National Action Plan in support of the Vision. One of the key themes of the National Action Plan is investing in innovation, supply and access, recognising that there are very few new antimicrobials being developed.

Investment in new antimicrobials, especially those that target multi-drug-resistant pathogens (also known as “superbugs”), is not commercially attractive because they are subject to strict controls to restrict their use to slow the development of resistance. This means sales could be low. The new payment method overcomes this by ensuring a fixed annual fee is paid to the company regardless of how many prescriptions are issued.

However, estimating the full value of new antimicrobials, and therefore what the annual fee should be, is complex and requires a different economic modelling approach. NICE’s current evaluation methods focus on health benefits for people that receive the drug, and sometimes their carers. For antimicrobials, the public health benefits go far beyond this. For example, effective antibiotics are essential in:

  • ensuring that chemotherapy, surgery and other medical procedures can go ahead
  • reducing the spread of infection to other people
  • providing a range of treatment options to reduce the risk of resistance developing and be prepared for existing antimicrobials becoming ineffective.
  • NICE is the first health technology assessment organisation anywhere in the world to attempt to estimate the full value of an antimicrobial in this way.

World Leading Innovations:

The draft NICE guidance will inform commercial discussions between NHS England and NHS Improvement and the companies to agree payment levels in subscription-style contracts. The payments will not be linked to the actual volumes of drugs used to treat patients in clinical practice but instead reflect the value of holding back new antimicrobials that infections have not become resistant to.

Secretary of State for Health and Social Care, Sajid Javid said: “Antimicrobial resistance is one of the biggest health threats facing the world and I’m incredibly proud that the UK’s world-leading innovations are helping to develop two antibiotics which will save many lives.

“NHS patients with severe resistance to other drugs could soon access these medicines, giving them a much greater chance of survival.

“It’s great to see international interest in this new development which will help incentivise investment in developing new antibiotics – together we can ensure our children can continue to treat common infections in the future.”

Programme Director in NICE’s Science, Evidence and Analytics Directorate, Nick Crabb said “This draft guidance represents an important milestone in the UK project. Its ultimate goal is to ensure the NHS has access to effective new antimicrobials to call on when needed and patients aren’t left without treatment options in the face of growing antimicrobial resistance.

“But we cannot address the global threat of antimicrobial resistance alone since the UK represents only about 3% of the global market for antimicrobials. We are sharing our learning from this project with international stakeholders and encourage other countries to offer similar incentives in their own domestic markets, so that collectively we can achieve a meaningful incentive for global investment in antimicrobials.”

“This is an important step in our world-leading approach to incentivise innovation in antimicrobial drugs and the battle against drug-resistant infections.

“The NHS will now use its commercial power to secure deals that will enable NHS patients to benefit from these treatments, delivering on its Long Term Plan commitment and paving the way for a pipeline of future treatment options.”

Blake Dark, NHS Commercial Medicines Director

When will NICE publish final guidance?

NICE will issue final guidance once the commercial discussions between NHS England and NHS Improvement and the drug manufacturers have concluded. NICE and its partners will work with stakeholders to review the approach taken in this project and develop routine arrangements for the evaluation and purchase of antimicrobials for the NHS.

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