GSK bags breakthrough status for bone cancer drug

GSK has claimed its second breakthrough designation from the FDA for antibody-drug conjugate GSK5764227, which it licensed from China's Hansoh Pharma in a $1.7 billion deal.

The status has been given to the B7-H3-targeted drug as a treatment for late-line relapsed or refractory osteosarcoma, a rare form of bone cancer with no FDA-approved treatments.

The coveted status can help speed up the development and regulatory review of drugs with the potential to treat a serious condition and where preliminary clinical evidence may indicate substantial improvement over currently available therapy.

The FDA previously designated the ADC as a breakthrough drug for relapsed or refractory extensive-stage small-cell lung cancer (SCLC), with the EMA awarding Priority Medicine (PRIME) status to the drug for this use last year.

B7-H3, also known as CD276, is an immunoregulatory protein that is overexpressed in tumour tissue, notably in lung, breast, ovarian, gastric, and brain cancer, as well as squamous cell carcinoma of the skin. It has limited expression in normal tissues, making it an interesting target for therapy that could avoid off-target side effects.

GSK said that the osteosarcoma designation is supported by data from the phase 2 ARTEMIS-002 study, an open-label trial that is evaluating GSK'227 in patients with relapsed or refractory osteosarcoma and other unresectable bone and soft tissue sarcomas, which is being conducted by Hansoh in China.

Initial results from the study reported at last year's ASCO cancer congress showed a 20% overall response rate with the ADC and a disease control rate – which includes stabilisation of the cancer – of up to 100%. GSK started an international phase 1 trial of the drug last summer.

Osteosarcoma mainly affects children and young adults and is the most common primary bone cancer, accounting for 20% to 40% of all bone cancers, according to GSK. Classed as a rare disease, it has an annual incidence of 3.3 patients per million in the US, representing less than 1% of all new cancer diagnoses.

At the moment, the first-line treatment is generally chemotherapy, with limited options for patients who don't respond or subsequently relapse.

GSK licensed rights to GSK'227 outside China, Hong Kong, Macao, and Taiwan in December 2023 for $185 million upfront and another $1.525 billion is potential milestone payments. A few weeks earlier, it tapped the Chinese biotech for a B7-H4 targeted ADC with potential in gynaecological cancers for $85 million upfront and up to $1.5 billion in milestones.

MSD and Daiichi Sankyo are currently at the forefront of drugmakers developing B7-H3-directed therapies, as they have already started phase 3 testing of their ifinatamab deruxtecan (I-DXd) ADC in patients with previously treated, extensive-stage SCLC.