Scientists react to news of MHRA approving gene therapy to cure sickle-cell disease.
Dr Rashid Kazmi, Honorary Senior Lecturer at the University of Southampton and Consultant Haematologist at University Hospital Southampton, said:
“We welcome the MHRA’s authorisation of this innovative new treatment for sickle-cell disease and transfusion-dependent β-thalassemia in patients aged 12 and over. This marks an important advance in providing new therapeutic options for patients suffering from these debilitating blood disorders. The rigorous assessment conducted by the MHRA provides assurance that the treatment has met robust standards for safety, quality and efficacy. We hope this treatment will make a significant difference to the lives of patients and their families who have long been hoping for better treatment alternatives.”
Dr Stephan Menzel, a Senior Lecturer at King’s College London, said:
“The new therapeutic approached is based on our group’s discovery at King’s that the molecular regulator protein BCL11A is involved in switching between the fetal and the adult for of haemoglobin. The adult form is defective in sickle cell disease and beta thalassaemia, and the new therapy releases the BCL11A off-switch on the fetal form, which functions normally.”
F cells measure the presence of fetal hemoglobin, a heritable quantitative trait in adults that accounts for substantial phenotypic diversity of sickle cell disease and beta thalassemia. We applied a genome-wide association mapping strategy to individuals with contrasting extreme trait values and mapped a new F cell quantitative trait locus to BCL11A, which encodes a zinc-finger protein, on chromosome 2p15. The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance.
Professor David Rueda, Chair in Molecular and Cellular Biophysics, Imperial College London, said:
“Today’s announcement that MHRA has approved Casgevy as the first gene therapeutic to treat beta-thalassemia is excellent news for the patients and the gene therapy scientific community. The published results of the clinical trial look very promising, too.
“However, it is well known that CRISPR can result in spurious genetic modifications with unknown consequences to the treated cells. It would be essential to see the whole-genome sequencing data for these cells before coming to a conclusion. Nonetheless, this announcement makes me feel cautiously optimistic.”
Prof Dame Kay Davies, Dr Lee’s Professor of Anatomy, University of Oxford, said:
“This is a landmark approval which opens the door for further applications of CRISPR therapies in the future for the potential cure of many genetic diseases. The challenge is that these therapies will be very expensive so a way of making these more accessible globally is key.”
Steve Bates, CEO of the U.K. Bioindustry Association, said:
“The U.K. is well set to be the first place in the world to licence, manufacture and provide access to gene editing treatments via an equitable health system.
“Not only do we have today’s world first regulatory approval via the MHRA but we already have in place the NHS innovative medicine fund as an explicit policy route to enable rapid adoption of innovation.
“In addition, the innovative U.K. medicine manufacturing community is playing a central role in developing manufacturing process for these novel therapies and NHS Blood and Transplant has for decades pioneered hospital processes needed to support advanced therapies.
“The U.K. didn’t win the Nobel for gene editing but we can develop a life science industry with new jobs and economic benefit from it based on our sustainable competitive advantages.”
Dr Alena Pance, Senior Lecturer in Genetics, University of Hertfordshire, said:
“This is a great step in the advancement of medical approaches to tackle genetic diseases we never thought would be possible to cure. Modifying the stem cells from the bone marrow of the patient avoids the problems associated with immune compatibility, i.e. searching for donors that match the patient and following immunosuppression, and constituting a real cure of the disease rather than a treatment.
“The exciting aspect of this is the strategy used for the gene editing, because blood diseases can be caused by a number of different mutations that it would be difficult to target individually. This therapy relies on switching off a transcription factor (BCL11A), which is a protein that enables the transition from foetal haemoglobin to adult haemoglobin at birth. This results in the making of foetal haemoglobin that can overcome the defects or absence of the adult beta globin, which makes this approach applicable independently of the specific mutation affecting beta globin present in individual patients.”
Prof Simon Waddington, Professor of Gene Therapy, University College London (UCL), said:
“Current treatments for thalassemia such as blood transfusions and chelating agents can have very unpleasant side effects.
“The approval of Casgevy is a tremendous advance in the treatment of beta thalassemia, a disease caused by a mutation in one of our hemoglobin genes. When we are born, our blood switches from a fetal type of hemoglobin to a post-natal form. People with thalassemia still have functional fetal hemaglobin even though it is switched off. Casgevy works by switching the fetal hemoglobin back on.
“However, this treatment may not easily scale up to be able to provide treatments in low and middle income countries, since it requires the technology to obtain a patient’s blood stem cells, deliver the genetic editor to these stem cells, and then reinjection of these cells. Therefore, it is not an “off the shelf” medicine that can be readily injected or taken in pill form.
“The patient also has to receive a type of medicine known as conditioning to kill off some of the bone marrow to make space for the corrected cells. This conditioning is known to have some side effects.
“Nevertheless, the current cure for thalassemia, a bone marrow transplant from another person still requires conditioning and, unlike Casgevy, carries the risk of graft versus host disease.”
Dr Helen O’Neill, Programme Director, Reproductive Science and Women’s Health, University College London (UCL), said:
“The future of life changing cures resides in CRISPR based technology. Genome editing has the potential to transform medicine but is currently typically applicable to blood based disorders due to the ability to transfuse blood. The use of the word “cure” in relation to Sickle cell disease or β-thalassemia has, up until now, been incompatible. The move by the MHRA to approve this therapy signals a positive moment in history.”
Dr Sara Trompeter, Consultant Haematologist UCLH and NHS Blood and Transplant, PI NIHR BioResource and Clinical Lead Sickle Cell Diverse Data Genomics England, said:
“Sickle cell disorder is a very complex life-limiting and life-threatening disorder with very limited treatment options. Whilst curative treatments may not be suitable for all, gene therapy offers a real chance of cure for those who are not eligible for bone marrow transplants and so we are delighted that it has been approved by MHRA. We look forward to NICE approval so that this can be delivered, free of charge to patients, in the NHS.”
Dr Helen O’Neill: No conflicts.
Dr Alena Pance: I declare no conflict of interest
Prof Simon Waddington: No conflicts
Dr Rashid Kazmi: No COIs to declare
For all other experts, no reply to our request for DOIs was received.