The importance of giving patients a voice in the approval of new sickle cell treatment

Patients and the public rely on the Medicines and Healthcare products Regulatory Agency (MHRA) to ensure that all medical products used in the UK meet the necessary standards of safety, effectiveness and quality. We are increasingly involving patients and the public in our work, to include their voice and experience in the regulatory process. This case study is an example of how the MHRA is benefiting from patients providing their lived experience for the pre-authorisation stage of the benefit-risk review.

More than 18,000 people in the UK suffer from sickle cell disorder. It is one of the most common genetic disorders in the UK.

Sickle cell, a familial condition where red blood cells become misshapen and fail to carry oxygen, “pervades all aspects” of patients' lives, “from relationships to work, for younger children school, university, any form of further education”, according to John James, CEO of the Sickle Cell Society.

Despite this, he added that “there has long been an under investment and under serving” of the condition, “and it's fair to say that people living with sickle cell and their families have felt ignored”. 

In November 2023, Casgevy, a new treatment for sickle cell disorder and transfusion-dependent β-thalassemia, was approved by the MHRA, the first regulator in the world to do so.

The role of patients in the approval process

A key part of the approval process was the involvement of patients with lived experience – an approach the MHRA intends to use more frequently. These patients gave valuable insight into the impact of sickle cell on their lives and the challenges of managing their condition. 

The MHRA collaborated with the Sickle Cell Society to identify three patients living with sickle cell disorder. 

The MHRA worked with these patients between April and August 2023. This began with introductory briefing sessions, before a meeting took place between each patient and an assessment team.

The questions in these meetings focused on understanding the patient's quality of life and experience of living with sickle cell, what they would want from a new treatment, and their views on gene therapies.  

Whilst a preliminary assessment for the licencing had already taken place – after the MHRA had thoroughly reviewed all the risks, benefits and data – the subsequent meetings with patients provided an incomparable depth of real-life insight into the impact of the disorder on a patient's quality of life. This is the human angle that cannot be conveyed so effectively in the written evidence.

The patients also responded very positively to the idea of this gene therapy as an option for treatment, with worthwhile benefits and an acceptable risk profile. This positive response, combined with the detailed patient perspective, supported the MHRA in its decision to licence Casgevy for the treatment of sickle cell.

By August 2023, the MHRA had incorporated the patients' contribution into its assessment of the product, and ahead of the approval of Casgevy in November, the patients were kept abreast of developments as the product went through the regulatory system.

One patient described what it meant to them to play a role in the approval of “this amazing new therapy, being used to help bring an end to the perpetual challenges that people like me live with”. 

“It was so important to me that the voices of people who live with the condition were heard and understood,” they said. 

“Making my contribution to a decision about such a life changing therapy is really important to me. Seeing it approved gives me hope for the future.” 

On the “huge impact” sickle cell has had on their life, they added: “The pain can be so unbearable, and taking care of your health and wellbeing is a full-time job when you've got sickle cell.  

“The condition affects my job, relationships and the lives of my loved ones who support me.  

“There are not enough medications available and that hasn't really changed in my lifetime.” 

Importance of patient involvement

“The MHRA is clearly an organisation that talks about involving patients and here is a real example of them doing so,” Mr James said. 

He explained: “There were a number of our members, of different ages and different genders, who took part in that conversation with the MHRA to inform the decision they made.

“The patients' involvement in the approval process was about sharing their experience of living with sickle cell and particularly the impact on their quality of life and the impact on wider family members. 

“What that process identified was what I would call a better understanding for the MHRA about what it means to live with this condition.” 

He added: “It's really important that patients are able to say and explain what it means to live with this condition, but equally what it means to have choices of effective treatment options.”

How Casgevy works

Casgevy is the first medicine to be licensed that uses the innovative gene editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020. CRISPR can precisely modify a piece of DNA or its chemistry in the human body. Its high precision is unparalleled and enables many uses including, in this case, gene therapy.

People with sickle cell have a mutation in their red blood cells. Normally, there's no treatment other than frequent blood transfusions or bone marrow transplants from a matched donor. Using CRISPR, it's possible to perform a one-time treatment to permanently correct the mutation.

It works by editing the faulty gene in a patient's bone marrow stem cells so the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient. Results have the potential to be a life-long cure. 

The treatment was approved following a rigorous assessment of its safety, quality and efficacy.

“The impact of this new treatment is that improvement in quality of life means people can work longer, potentially live a very fulfilling and active life, which can only be good for the UK economy,” Mr James said.

Julian Beach, Interim Executive Director of Healthcare Quality and Access at the MHRA, said: “The patients involved in the licensing of Casgevy helped us gain a thorough understanding of the impact of sickle cell on the quality of their lives and the significant challenges that come with it.  

“This was invaluable to the approval process of such an important treatment. 

“Thank you to the patients for giving up their time to make such a crucial contribution. We recognise, too, the personal effort involved in doing that. Thank you also to the Sickle Cell Society for facilitating this. This approach is one we intend to use more frequently.”

A decision on patient access to Casgevy for sickle cell disorder through the NHS will be made through the National Institute for Health and Care Excellence (NICE) independent committee process in due course.