Loxo, Blueprint drive forward with RET-targeting cancer therapies
- No therapies are currently approved in the U.S. to specifically treat cancers driven by changes in an oncogene known as RET. Updated clinical results from two drugs in development by Loxo Oncology and Blueprint Medicines, however, suggest that might not be the case for too much longer.
- Data presented over the weekend at the annual meeting of the American Thyroid Association, while early, gave further evidence of the two therapies' effectiveness in inhibiting RET signaling in patients with two types of thyroid cancer.
- Treatment with LOXO-292 led to a 59% overall response rate (ORR) in 29 patients with RET-mutated medullary thyroid cancer (MTC), and nearly half of 35 evaluable MTC patients on Blueprint's drug experienced a response, results showed. While adverse events were common, few patients in either study experienced severe side effects.
Targeted therapies are enjoying a renaissance of sorts, with new drugs designed to seek out specific tumor weak spots emerging for the treatment of breast, lung and ovarian cancers, among others.
With LOXO-292 and BLU-667, Loxo and Blueprint are working to add to the list of addressable genetic targets.
Alterations in the RET gene occur in an estimated 1% to 2% of all non-small cell lung cancer cases. By contrast, RET mutations are found in approximately 60% of medullary thyroid cancers, while between 10% and 20% of papillary thyroid cancers test positive for RET fusions, according to Loxo.
These cancers are highly dependent on activation of the RET kinase for their growth, making small molecule inhibitors of RET signaling a promising treatment approach.
Loxo presented data from its LIBRETTO study of LOXO-292 earlier this year at the American Society for Clinical Oncology's annual meeting. Updated results now include data from seven more patients and show an increased ORR and continued treatment tolerance. Patients enrolled in the study are heavily pretreated, with a median of three prior systemic therapies.
In Blueprint's ARROW study, treatment with BLU-667 resulted in a 49% ORR among the 35 patients evaluable for response assessment. The biotech noted, however, that the ORR ticked up to 62% among patients treated with higher doses of the drug for at least six months.
Despite the temptation to compare the studies, one Wall Street analyst highlighted that differences in design between the two could confound a cross-trial analysis.
"LOXO-292's dose escalation permits intrapatient dose escalation, in addition to a traditional cohort approach. This design may confound direct comparison of response rate data between the two trials," wrote Leerink analyst Andrew Berens in a Oct. 8 note to investors.
Intrapatient dose escalation, Berens explained, could boost the chances a patient responds to treatment as the amount of drug being administered increases. In a study with fixed doses, by comparison, those patients on a lower treatment regimen may be less likely to respond. (Assuming, of course, a clear dose/response correlation.)
Investors didn't appear to draw any clear conclusions, with shares in both companies opening lower at the start of Monday trading.
Berens, though, sees the latest snapshot as supportive of the role LOXO-292 and BLU-667 could eventually play, if clinical testing continues to prove positive.
"We see both agents continuing to produce compelling efficacy and safety, and believe both will be used in RET driven cancers," Berens wrote.
- BioPharma Dive So far, so good for Loxo's gene-focused cancer therapy
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