Loxo RET inhibitor shines in early-phase trial

Loxo CEO Joshua Bilenker, M.D. (Loxo Oncology)

Loxo Oncology has reported encouraging data from a phase 1 trial of RET inhibitor LOXO-292 in solid tumor patients. The drug shrunk the tumors of most patients in the trial, raising hopes it can become a new treatment option for patients with RET-altered cancers.

As of Jan. 5, Loxo had treated 57 people. Almost half of the patients had RET fusion-positive non-small cell lung cancer (NSCLC). Most of the remaining participants had either RET fusion-positive papillary thyroid cancer (PTC) or RET-mutant medullary thyroid cancer (MTC). Patients with these RET alterations are poorly served by multikinase inhibitors. 

In an abstract released ahead of the 2018 ASCO Annual Meeting, Loxo focused on the response rate in the NSCLC and PTC patients. The overall response rate (ORR) in these RET fusion-positive patients came in at 69%. The tumors of the patients shrunk in size by as much as 67%.

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Loxo also reported tumor shrinkage in the majority of MTC patients, but in most cases the change fell short of a partial response. Just two of the 14 evaluable MTC patients experienced partial responses. 

The performance of LOXO-292 in the MTC cohort dragged the ORR across the whole trial down to 52%. But with Loxo stating that the April cutoff data it is presenting at the 2018 ASCO Annual Meeting are better than those shared this week, the results were nonetheless strong enough to make the biotech a standout performer among the abstracts released ahead of the event.

The data sparked an 18% rise in Loxo’s stock after hours and sent out waves that affected rival firms. Notably, shares in Blueprint Medicines fell 10% as investors made unfavorable comparisons between its RET inhibitor, BLU-667, and Loxo’s LOXO-292.

It remains to be seen whether that is a fair reflection of the drugs’ prospects. In April, Blueprint presented phase 1 data linking BLU-667 to an ORR of 45%. That is slightly below the 52% ORR seen in the Loxo trial. Bigger differences were seen in subgroups, notably the 19-percentage-point divergence in ORR in NSCLC patients. But given the difficulties of comparing across trials—and the fact that a minority of patients in Blueprint’s trial received the optimized dose—BLU-667 could still come out on top.

Blueprint and Loxo are both working to move into the next phase of development and pick up early approvals. The trials will go some way to clearing up doubts about both existing data sets. But, when combined with strong safety data generated to date, the efficacy results already suggest that Blueprint’s and Loxo’s drugs could challenge existing RET products from Exelixis and Sanofi.