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RET rivals Loxo and Blueprint face off with early-stage data

No clear winner between RET inhibitor rivals

Two companies developing RET inhibitors for cancer – Loxo Oncology and Blueprint Medicines – have gone head-to-head with data readouts that have analysts trying to pick an eventual winner.

Loxo unveiled new data from a phase 1/2 study of its LOXO-292 candidate in RET-mutated thyroid cancers, with a 59% overall response rate in medullary tumours and 78% in fusion-positive tumours after a median follow-up of around 8.5 months. Tumours reduced in size in 94% and 100% of patients, respectively.

The results update three-month data reported earlier this year at ASCO and suggest the drug is able to achieve “durable responses in heavily pre-treated patients with RET-driven cancers,” according to investigator Lori Wirth of Harvard Medical School and Massachusetts General Hospital.

Blueprint’s data with its BLU-667 candidate didn’t seem so strong on the face of it, with the obvious caveat that there were differences between the two studies in terms of design and enrolled subjects. Its shares were down a couple of points after while Loxo tracked upwards by around the same margin.

The ARROW trial revealed that 90% of patients with RET-altered medullary and papillary thyroid cancers had reduction in tumour volume overall, with a 62% response rate in medullary patients treated with BLU-667 for at least 24 weeks, and 49% across all patients with that type of cancer. In papillary tumours, two of four patients had a partial response and all showed evidence of tumour shrinkage.

“Existing treatment of medullary and papillary thyroid cancer with multi-kinase inhibitors is limited by frequent dose modifications or interruptions due to off-target toxicities, reducing the opportunity for a meaningful or sustained response," said the company’s chief medical officer Andy Boral.

“These new data showed selectively targeting RET alterations with BLU-667 was well-tolerated and enabled durable responses,” he added, noting that some patients continued to respond to the drug for up to 15 months.

There are no approved RET-targeting drugs and the new data – presented over the weekend at the annual meeting of the American Thyroid Association – provides further proof of concept for the mechanism.

It’s really too early to make any judgment between the two drugs, according to Leerink analyst Andrew Berens, who noted: “we see both agents continuing to produce compelling efficacy and safety, and believe both will be used in RET-driven cancers.”

Article by
Phil Taylor

9th October 2018

From: Research

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