A response from the Bone Cancer Research Trust & FAQs
What is the FDA?
The Food and Drug Administration (FDA) is the regulatory agency responsible for ensuring safety, efficacy, and quality of all medicines and medical devices in the USA through rigorous processes of review and approval. The European Medicines Agency (EMA) is the European equivalent.
Since the UK withdrew from the European Union, the EMA's regulatory authority applies to Northern Ireland only; for the rest of the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) is responsible for all medicine and medical devices regulation.
What is GSK'227 and how does it work?
GSK'227, also known as HS-20093, is a type of drug known as an antibody-drug conjugate (ADC), which delivers chemotherapy to cancer cells by recognising a specific target. ADCs combine a protein (called a monoclonal antibody) and a chemotherapy drug. The monoclonal antibody is itself a targeted therapy that's able to target and kill cancer cells by recognising a specific protein on their surface.
Within an ADC, the antibody is joined to and acts as a vehicle for the chemotherapy drug. In the case of GSK'227, the antibody recognises a specific protein target (known as B7-H3) which is highly present on the surface of cancer cells, but much less so on the surface of normal, healthy cells. The antibody therefore delivers the chemotherapy in a targeted way.
What does 'Breakthrough Therapy Designation' mean?
The FDA's 'Breakthrough Therapy Designation' is a process designed to speed up the development and review of drugs intended to treat serious or life-threatening conditions, such as primary bone cancer, with the aim of fast-tracking the timeline from laboratory to clinic. It is granted where early evidence has indicated that a drug may show 'substantial improvement' for patients.
'Breakthrough Therapy Designation' does not mean that a drug has already been proven as a breakthrough treatment. Rather, it means that preliminary findings have demonstrated its potential as an effective treatment (when compared to current standard therapy or where there are no other options) and warrant putting more resources into streamlining the drug's development and prioritising its review.
In fact, analysis performed by the FDA found that the development time could be reduced by approximately 30% when compared to drugs without this special designation.
Regardless, the safety and efficacy of all new drugs must be thoroughly investigated across different phases of clinical trails before they can be approved for use in patients. The ARTEMIS-002 phase 2 clinical trial investigated GSK'227 in patients with osteosarcoma and other sarcomas which have returned (relapsed) or have not responded to treatment (refractory). Early results gathered from over 60 patients, including 42 with osteosarcoma, demonstrated promising indications of efficacy (anti-tumour activity) balanced with an acceptable degree of toxicity (side effects).
On this basis, the FDA granted 'Breakthrough Therapy Designation' to GSK'227 for the treatment of adult patients with relapsed or refractory osteosarcoma, whose disease progressed on or at least two prior lines of treatment.
What are the next steps?
Whilst Breakthrough Designation Status has been granted, GSK'227 must be approved before reaching patients.
FDA approval is dependent on rigorous review of all the evidence from all phases of clinical trial. If FDA approval is granted, drugs must be approved for use in the UK by the MHRA, via the International Regulation Procedure.
Further evidence must now be gathered within clinical trials and be reviewed by the FDA (and other equivalent regulatory agencies) before GSK'227 is approved as a treatment for relapsed and refractory osteosarcoma. A new trial has been initiated, which will test GSK'227 in centres across the US, South America, Canada, and Japan to gather this information. However, achieving Breakthrough Therapy Designation status is a significant step forwards and will help to save precious time for patients & families faced with limited options.
Although this trial is not currently available in the UK, we look forward to monitoring its progress and we will share further news as it becomes available.
Further information
How does the FDA approve new drugs?
What's the FDA's role in regulating drugs?
References and further reading
https://www.fda.gov/patients/fast-track-breakthrou...
https://www.fda.gov/regulatory-information/food-an...
https://my.clevelandclinic.org/health/treatments/a...
https://www.precisionformedicine.com/blog/what-is-...
https://aspe.hhs.gov/reports/fda-breakthrough-ther...
Xie L, Xu J, Sun X, Liang X, Liu K, Yang Y, Ji T, Wang G, Shen J, Hu H, Hua Y. ARTEMIS-002: Phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma. Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.2024.42.1...
https://www.cancerresearchuk.org/about-cancer/find...
https://www.gov.uk/government/publications/interna...