According to the BBC, the National Health Service (NHS) in Great Britain has confirmed the treatment of an 11-year-old patient suffering from leukemia with the CAR-T cell therapy Kymriah at the Great Ormond Street Hospital (GOSH) in London. This is a first sign that CAR-T gene and cell therapies are slowly but surely being acknowledged by the public. However, it yet remains to be seen whether this therapy, which may prove vital for certain patients, is without negative side effects or consequences for said patients. And this certainly is cause for concern.
11-year old Yuvan Thakkar could not be healed with traditional leukemia therapies, which is why the responsible doctors at the Great Ormond Street Hospital (GOSH) in London – in agreement with the parents – decided to treat the young patient with a new kind of therapy that up until then in the UK had only been tested in clinical research studies.
A CAR-T cell therapy comprises the already established immune therapy and extends the treatment to include cell and genetic therapy. CAR-T is short for “chimeric antigen receptor T-cells”, which are transformed into aggressive tumor killers by means of genetic mutation.
T cells are an element of the human immune system; in normal cases, however, they cannot detect and fight tumorous cells – they rather offer protection from attacks that happen as a result of molecular modifications. However, once manipulated, T cells can clearly recognize tumorous cells as a threat to the body and in turn will start to attack them.
What may sound like a simple and straightforward process is in reality a highly complex procedure that scientists have been working on for many years already. Every single therapy has to be tailored to the respective patient, which poses enough challenges in itself.
In short, blood is taken from the patient and the proprioceptive defense cells (T cells) are manipulated. Once they have been reapplied, they can actively fight the tumor cells.
In 2012, 6-year-old Emily Whitehead, who was suffering from leukemia, received a CAR-T cell therapy. The specialists had already given up hope, as none of the other applied therapies had proven successful. Emily Whitehead is the first child known to be healed thanks to a CAR-T cell therapy. Her case is regarded as a milestone in the medical field.
According to the BBC, the compound KYMRIAH (Novartis) that is used for the treatment of Yuvan Thakkar (11) amounts to 370,000 $. The same article mentions that the NHS is in negotiations with Novartis for reduced costs in the case of a more frequent application of the therapy.
One of the main issues of the CAR-T cell therapy is no less than banal – it is logistics. The pharmaceutical industry, which is focused on shipping large amounts of drug substances, is lacking reasonable and realistic solutions for the agile and secure worldwide shipping of small batches that are required for the CAR-T cell therapy, where frozen bags with a volume of 50 ml to 0.5 L are sufficient. It is a known fact among biopharmaceutical players that around 1% – 3% of therapies are rendered useless due to loss of drug substance. Unmonitored disruptions of the cool chain or material deficiencies of single use bags that lead to bio contamination during the filling process are among the most common reasons for loss of drug substances.
Future outlook: Today, the new therapy can be used for the treatment of five severe medical conditions. However, approx. 300 further CAR-T therapies are currently being developed, 110 of which are designated for the treatment of various tumor diseases. More than half of these 111 promising therapies are currently being tested in phases I to III. 20 more CAR-T cell therapies are expected to be entering phase IV, the full approval by the FDA, in the near future.
“Safe and secure logistics” remains a bottleneck, and is expected to become an even bigger issue with the increasing number of available therapies. The biopharma industry will keep trying to apply unsuited existing, and at times aged, solutions while patients often have to keep waiting for their therapies that have been damaged during the shipping process.
Single Use Support GmbH have not only found a solution for this issue, but they have developed an entire process. They took the bottleneck and transformed it into a solution, which allows to push patient safety to a whole new level.
More details regarding the test phases of a therapy prior to its approval:
Phase I: Initial trial of a drug in humans for dosing, safety, and early efficacy information (20-80 patients*)
Phase II: Subsequent trial of a drug’s safety and efficacy in a particular disease setting (100-300 patients*)
Phase III: Larger trial comparing a drug with best available therapy to confirm efficacy and safety; often used for drug approval (1,000-3,000 patients*)
Phase IV: Trial conducted after US Food and Drug Administration (FDA) approval to gain additional information about the drug’s risks and benefits (thousands of patients*)
*The patient numbers cited here apply to clinical trials in general.
RoSS KSET – the perfect container for transport, safety and freeze-thaw process for each individual CAR-T cell therapy: