GIST Market Comes Of Age

Patent expiries, novel pipeline treatments, and more patients are set to shake up the gastrointestinal stromal tumor market, finds Datamonitor Healthcare.

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The market for GISTs (or gastrointestinal stromal tumors), an indication that sprang to the fore with the arrival of targeted therapies for cancer, is about to undergo change as the pioneering drugs come off patent, and newer more varied therapies come through the pipeline. Meanwhile the number of cases is also set to increase, finds Datamonitor Healthcare in a new Market Spotlight.

Standard chemotherapy is usually ineffective in GIST so the coming of targeted therapies against tyrosine kinase revolutionised treatment of the disease when surgery alone was not enough. These tyrosine kinase inhibitors (TKIs) target a protein that helps with tumor growth and survival.

The first was Novartis AG's Gleevec back in 2002, then Pfizer Inc.'s Sutent (sunitinib), followed by Bayer AG's Stivarga (regorafenib) in 2013. These target platelet-derived growth factor receptor (PDGFR), BCR-ABL fusion protein, vascular endothelial growth factor (VEGF) receptor, KIT/c-KIT, Raf kinase, and FMS-like tyrosine kinase 3.

But genericization is upon the market. Gleevec is already off patent, and Sutent’s US method of use patent is set to expire in December 2020, which will open the door to generic entry. Stivarga is set to follow suit in 2022.

What are GISTs?

GISTs are the most common mesenchymal neoplasms of the digestive tract, representing less than 1% of gastrointestinal (GI) tumors and around 5% of sarcomas. Most GIST cases arise in the stomach, and the majority of the remaining cases begin in the small intestine, but they can begin anywhere in the GI tract, as well as areas outside the GI tract such as the peritoneum and omentum. Metastasis occurs most commonly in the liver and omentum, and less commonly in the lungs. Bone and local lymph node metastases are rare.

But as these drugs approach the end of their patent lives, new products are coming through the pipeline aimed at a variety of drug targets, the report found. Using the Biomedtracker database, they highlight seven candidates in the pipeline at Phase II-III:

Drug	Generic	Lead	Target(s)	Phase
Masitinib	masitinib mesylate	AB Science	Fibroblast growth factor receptor (FGFR), KIT/c-KIT, Platelet-derived growth factor receptor (PDGFR)	III
Crenolanib	crenolanib besylate	AROG Pharmaceuticals	FMS-like tyrosine kinase 3 (FLT-3), Platelet-derived growth factor receptor (PDGFR)	III
AT13387	onalespib	Otsuka Pharmaceutical Co. Ltd.	Heat shock protein 90 (HSP90)	II
Binimetinib	binimetinib	Array BioPharma Inc.	Mitogen-activated ERK kinase (MEK, MAPKK, MAP2K)	II
Evofosfamide	evofosfamide	Molecular Templates Inc.	DNA	II
Iclusig	ponatinib	Takeda Pharmaceutical Co. Ltd.	BCR-ABL fusion protein, Fibroblast growth factor receptor (FGFR), FMS-like tyrosine kinase 3 (FLT-3), RET, VEGF receptor (VEGFR)	II
Votrient (oral)	pazopanib	Novartis AG	KIT/c-KIT, Platelet-derived growth factor receptor (PDGFR), VEGF receptor (VEGFR)	II

Further back in the pipeline there is more evidence of innovation. Phase I data for Blueprint Medicines Corp.'s kinase inhibitor BLU-285 prompted the US FDA to grant a breakthrough therapy designation for the treatment of a small, genetically defined group of patients with GIST, which could result in approval based on positive results from the expansion cohort of the early-stage clinical trial. SC098887

And the market is set to grow. Datamonitor Healthcare estimates that in 2016, there were 96,400 incident cases of GIST worldwide, and expects that number to increase to 105,600 incident cases by 2025.

It is estimated that Asia had the largest number of incident cases in 2016 (62,600 cases), while the Oceania region had the lowest number of incident cases (500 cases).