Autolus Therapeutics, a UCL spinout company, has received U.S. Food and Drug Administration (FDA) approval, for a next-generation CAR-T cell therapy, developed to treat adults with an aggressive blood cancer.
The personalised therapy, named Obecabtagene autoleucel (obe-cel) and marketed as AUCATZYL®1, is for patients with advanced relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), and is the biopharmaceutical company's first FDA approved product.
Obe-cel was designed by UCL scientists, in work led by Dr Martin Pule at UCL Cancer Institute, along with collaborators at the UCL Great Ormond Institute of Child Health2. Dr Pule leads the UCL CAR T cell programme3 which is supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre (BRC).
Manufacture of this advanced therapy was developed at the CCGTT, Royal Free Hospital. Clinical development in adult B-ALL was built on the ALLCAR19 clinical study4, led by UCLH and supported by grant funding from the NIHR.
Around 8,400 new cases of ALL are diagnosed every year in the US and EU. Of these, over 3,000 will either relapse or not respond to standard treatment. For adult patients with r/r ALL, prognosis is poor with a median overall survival of eight months.*
Obe-cel was approved by the FDA based on results from the Autolus FELIX clinical trial4 in adult patients with r/r B-ALL. In the 65 patients where efficacy could be evaluated, 63% achieved overall complete remission, representing the elimination of all signs of cancer in response to treatment. Complete remission within three months was achieved in 42% of patients, with a median duration of remission of 14.1 months.
Dr Claire Roddie, lead investigator of the FELIX study and Associate Professor of Haematology at UCL Cancer Institute, said: "Based on the experience in the FELIX trial AUCATZYL/obe-cel is highly active and can be well managed, offering an attractive risk benefit profile for B-ALL patients.
"In the FELIX trial AUCATZYL/obe-cel has shown long term persistence and deep responses which we believe are critical for long term remissions in B-ALL."
In 2018, UCLB and Autolus entered into a licence agreement for patent rights relating to obe-cel.
Additionally, through the UCL Cancer Trials Centre, the university has a long-term strategic collaboration with Autolus and have conducted obe-cel clinical studies in paediatric and adult patients with r/r B-ALL and in patients with r/r B-cell Non-Hodgkin's Lymphoma4.
Marketing authorisation applications (MAAs) for obe-cel in adult r/r ALL are being reviewed by the regulators in both the EU and the UK.
UCL Business (UCLB) has supported Autolus in protecting and licensing the obe-cel technology enabling it to attract further capital for to fund its development.
Dr Rick Fagan, Director of BioPharm, UCL Business (UCLB), said: "This news is a great example of industry and academic collaboration delivering real impact.
"It has been exciting to support Autolus and see its paradigm-shifting advanced therapeutic reach this hugely important stage."
Dr Martin Pule, Director of the UCL CAR T cell programme, founder of Autolus and Chief Scientific Officer of Autolus said: "success in developing obe-cel shows what can be achieved through collaboration between UCL, its affiliated hospitals and industry".
AUCATZYL will be manufactured at Autolus' commercial manufacturing site in Stevenage, UK, which will supply the therapy globally.
What is CAR T-cell therapy?
CAR T-cell therapy involves collecting a patient's own white blood cells (T-cells, responsible for fighting infection), 'reprogramming' them in the laboratory to seek and 'fight' the cancer cells and giving them back to the patient via infusion.
For the FELIX trial, patients had their T cells genetically modified with a new type of CAR called obecabtagene autoleucel or obe-cel6.
This treatment programmes immune T cells to make an artificial protein called a CD19 chimeric antigen receptor (CAR) on their surface, directing them to specifically recognise cancerous cells.
Obe-cel has been designed to overcome two common constraints associated with 'first generation' CAR T-cell therapies.
One problem was that the immune system became over-activated, causing a toxic reaction called 'cytokine release syndrome.' The other problem was that T-cells were not able to persist in a patient's body.
1AUCATZYL® is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
2 Research paper published in Nature Medicine September 2019
4Research paper published in Journal of Clinical Oncology September 2021
5 Research paper published in Blood November 2023
6Research paper published in Blood November 2023
