oxo Oncology has earned considerable buzz and a hefty stock market valuation for bringing a genomic-based approach to cancer drug development. The Connecticut biotech’s drugs target highly specific genetic mutations found in cancer cells, regardless of where in the body the tumor is located.
The first of Loxo’s experimental drugs, larotrectinib, has already demonstrated a strong cancer-killing ability in tumors with a genetic alteration called a TRK gene fusion. The drug is under FDA review with an approval decision expected in late November.
On Saturday, Loxo is unveiling clinical trial data for the first time showing a second drug, LOXO-292, is equally capable of eliminating tumors containing a mutated protein known as RET.
In a presentation at the American Society of Clinical Oncology annual meeting in Chicago, LOXO-292 shrank tumors in 77 percent of patients with so-called RET fusion cancers. Most of the 49 patients had tumors that originated in the lungs but some were classically defined as thyroid and pancreatic cancers.
Separately, the Loxo study also enrolled 29 patients with RET-mutated medullary thyroid cancer. Here, the response rate was 45 percent.
The tumor responses to LOXO-292 have been durable. None of the responding patients has relapsed to date, with the longest-followed patient still on therapy 10 months since beginning treatment. The drug’s safety profile has not raised any red flags, with just two serious adverse events reported.
“The question one needs to ask about targeted therapeutics is, do we have the right drug for the right target? And here, the answer seems to be yes. This is a nice study,” said Dr. Ravi Salgia, a lung cancer expert at the City of Hope in Los Angeles. Salgia was not involved in the Loxo study.
There was only a single complete response recorded in the LOXO-292 study in a medullary thyroid cancer patients. The remaining tumor responses were partial, which is a concern for Salgia.
“This is a Phase 1 study where they are still trying to find the right dose, so it will be important to look at future data to see if patients can achieve complete responses,” Salgia said.
RET fusions are found in 2 percent of lung cancers and 10 percent to 20 percent of certain thyroid cancers. The mutation is also found in 60 percent of medullary thyroid cancers.
The LOXO-292 results mirror almost perfectly the 76 percent response rate delivered by larotrectinib in TRK fusion tumors at last year’s ASCO meeting.
In November, German pharma giant Bayer paid Loxo $400 million in upfront cash and promised another $650 million in contingency payments in exchange for marketing rights to larotrectinib and a follow-on drug.
Loxo retains full ownership of LOXO-292. CEO Josh Bilenker says the company’s plan is to expand enrollment in the current study to gather more data before meeting with the FDA about filing plans. If larotrectinib serves as a precedent, Loxo should be able to submit LOXO-292 for approval in RET fusion cancers based on the current clinical trial. An additional randomized, controlled study will likely be required to secure approval in RET-mutated medullary thyroid cancers, Bilenker said.
Blueprint Medicines is also developing a drug that targets RET mutations. In a study presentation earlier this spring, the Blueprint drug, called BLU-667, showed a 50 percent response rate in RET fusion tumors and a 40 percent response rate in MTC-mutated medullary thyroid cancers.
At Friday’s closing price of $186.69, Loxo shares are up nearly 30 percent since May 16 when ASCO research abstracts, including an early peek at LOXO-292, were made public. Saturday’s updated results were stronger across the board. Loxo’s market value is now $5.6 billion.