A teenager who has lost family members including her mother because of a rare genetic hereditary illness has become the first patient in the UK and Europe to have a new treatment developed by Cambridge researchers and approved for use on the NHS.
It is incredible to go from the discovery of a new disease in Cambridge to a treatment being approved and offered on the NHS, within the space of 12 years
Anita Chandra
Mary Catchpole, 19, was given a newly licensed drug called leniolisib (or Joenja) at Addenbrooke's Hospital in Cambridge. It is the first ever targeted treatment for a rare, inherited immunodeficiency called Activated PI3-Kinase delta syndrome (APDS).
People with APDS have a weakened immune system, making them vulnerable to repeated infections and autoimmune or inflammatory conditions. Discovered just over a decade ago by a team of Cambridge researchers, it is a debilitating and life-threatening condition, with patients more likely to develop blood cancers like lymphoma.
APDS is a relatively new immuno-deficiency, with Mary's family playing a key role in its discovery in 2013. Mary's mother and uncle, who were Addenbrooke's patients, were offered DNA sequencing (whole exome sequencing) to see if there was a genetic cause for their immuno-deficiency.
Cambridge researchers identified a change in their genes that increased activity of an enzyme called PI3-Kinase delta, resulting in the illness being named Activated PI3-Kinase delta syndrome (APDS).
The team, which involved researchers from the University of Cambridge, Babraham Institute, MRC Laboratory for Molecular Biology, and clinicians from Addenbrooke's, was primarily funded by Wellcome and the National Institute for Health and Care Research (NIHR).
With APDS, the enzyme PI3-Kinase delta is "switched on" all the time, preventing immune cells from fighting infection and leads to abnormal or dysregulated immune function.
The new treatment - with one tablet taken twice a day - aims to inhibit the enzyme, effectively normalising the immune system.
Dr Anita Chandra, consultant immunologist at Addenbrooke's and Affiliated Assistant Professor at the University of Cambridge, said: "It is incredible to go from the discovery of a new disease in Cambridge to a treatment being approved and offered on the NHS, within the space of 12 years.
"This new drug will make a huge difference to people living with APDS, hopefully allowing patients to avoid antibiotics, immunoglobulin replacement and potentially even a stem cell transplant in the future."
Professor Sergey Nejentsev from the University of Cambridge who led the research that discovered APDS said: "As soon as we understood the cause of APDS, we immediately realised that certain drugs could be used to inhibit the enzyme that is activated in these patients. Leniolisib does precisely that. I am delighted that we finally have a treatment which will change the lives of APDS patients."
The disorder has significantly impacted Mary's family on her mother's side. Her aunt died aged 12, while her mother, uncle and grandmother all died in their 30s and 40s.
Mary works as a teaching assistant and lives in Great Yarmouth, Norfolk with her father Jimmy and older brother Joe, who does not have the condition.
Prior to leniolisib, the only treatments available to APDS patients include antibiotics for infections, immunoglobulin replacement therapy (to prevent infections and damage to organs) or a bone marrow or stem cell transplant, which can be a potential cure but carries significant risks.
Mary said: "Having APDS means I've got a higher chance of infections and getting unwell, which is hard when all I want to do is work and dance and have adventures. All my life I've had to have weekly infusions which make me feel like a pin cushion, and I've had to take lots of medication which has been tough.
"Now that I have this new treatment, it does feel bitter-sweet as my late mum and other affected members of my family never got the chance to have this new lease of life, but it is a gift. I feel blessed."
Leniolisib was licensed for use in America in 2023, following clinical trials. After assessment and approval by the UK medicines regulator, the MHRA, it is now approved by NICE (National Institute for Health and Care Excellence) for NHS use - the first health system in Europe to use it to treat patients with APDS.
Professor James Palmer, NHS England's Medical Director for Specialised Commissioning, said: "We're delighted to see Mary become the first patient in Europe to receive this first-ever targeted and approved therapy for a rare condition identified just over a decade ago - in Cambridge no less.
"This treatment could be life-changing for those affected by this debilitating genetic disorder, and this important step forward is another example of the NHS's commitment to offering access to innovative medicines for those living with rare conditions."
As a tertiary centre for immune-deficiencies, patients eligible for leniolisib can be referred to Addenbrooke's, part of Cambridge University Hospitals NHS Foundation Trust, for specialist review and care and ongoing research in this rare condition.
Dr Susan Walsh, Chief Executive Officer at Immunodeficiency UK, said: "With leniolisib, we now have a targeted treatment available that addresses the fundamental cause of the immune system problems experienced in APDS. This demonstrates the power of research and is a huge leap forward. The new treatment will help improve the quality of life for those families living with APDS."
By looking at the role of the enzyme linked to APDS and the impact of the new targeted drug on the patient's immune system, it is hoped there is potential for leniolisib to be applied to other more common immune related conditions in the future.
Adapted from a press release from Cambridge University Hospitals.
