#ASH20 UPDATED: Loxo and Eli Lilly show off PhI/II data for their BTK inhibitor in two blood cancers – Endpoints News

ASH is back and Loxo is primed and ready to present new data that they think will be quite exciting.

The Lilly-owned company is announcing results from a Phase I/II trial on its LOXO-305 program, and Saturday afternoon they detailed data in patients with mantle cell lymphoma (MCL) and other non-Hodgkin lymphomas. And Monday morning, Loxo added to their data portfolio with results from the program in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma.

LOXO-305 itself is a Brutons tyrosine kinase (BTK) inhibitor, drugs which themselves are not new, Loxo COO Jacob Van Naarden told Endpoints News. Tens of thousands of cancer patients use the drugs every year, mainly in leukemia and some types of lymphomas, he said. But patients typically develop resistances to the drugs after a while, and in a highly aggressive cancer like MCL they typically dont have any options after the drugs stop working.

Why does this happen? Most of the BTK inhibitors already on the market are, in a sense, very sticky. They use covalent bonds to attach to the BTK receptors and block the activity, choking off the necessary chemicals that these cancers need to function. Patients eventually develop mutations to the BTK gene, however, stopping the drugs from sticking any longer.

Where LOXO-305 is different, Van Naarden says, is that it doesnt use this type of bond it becomes reversible. That allows the drug to stay in a patients bloodstream long enough before they have to take the next dose. LOXO-305 is a once-daily pill.

Whats exciting about the data were presenting at ASH is that they show LOXO-305 is really a truly differentiated BTK inhibitor in its ability to induce new responses in these patients relapsing on the covalent drugs, Van Naarden said.

Loxo enrolled 323 patients in the entire trial, with a little over half (170) having CLL. Among the 139 evaluable CLL patients, Loxo saw a 63% overall response rate after a median of 6 months, as well as improving rates over time 25 of the 29 patients who had been on the treatment for at least 10 months demonstrated at least a partial response.

In this disease, LOXO-305 also showed good efficacy regardless of a patients prior treatment history, the company said. The median CLL patient received 3 prior lines of therapy a heavily pre-treated population compared to studies of BTK inhibitors in the past, CMO David Hyman said.

Nearly every patient has some degree of tumor regression [in CLL], Hyman told Endpoints News.Theres lots of available treatmentsbut no matter how you look at the prior treatments that patients can get, including patients that have received some and even patients that have received all of these treatments, the response rate doesnt really seem to change.

In MCL the portion, the trial enrolled 61 patients who received a median of three prior therapies, and 56 of those 61 were evaluable for the results. Out of the 56 patients, 29 achieved at least a partial response, with 14 registering complete responses. Thats good for a 52% overall response rate as of the Sept 27 data cutoff, and most of the patients who achieved the best responses are continuing treatment, including 24 of the 29 who saw a response.

On safety, Loxo grouped all 323 patients together regardless of cancer type. The most common side effects across the trial were fatigue, diarrhea and bruising. There were eight adverse events that hit Grade 3 four in hypertension, three in fatigue and one from a hemorrhage, though investigators noted that event was the result of a bike accident and not related to the treatment. Five of the 323 patients discontinued treatment due to adverse events.

Van Naarden and Hyman said they hope these data can boost LOXO-305s case to become the standard of care in patients who have already received treatment. Hyman emphasized that even among the pre-treated 52 MCL patients a much more aggressive disease than CLL the ORR stayed the same.

To see that combination of an initial response to treatment and what looks like an ongoing response over months of additional treatment, thats really, really unusual, Hyman said.

With Saturdays data now in hand, Loxo is planning on moving forward with a Phase III trial that pits the candidate head-to-head against another BTK inhibitor in MCL patients. And in CLL, Loxo is planning three Phase III studies, two of which will take a further look at those who have received prior BTK inhibitors in addition to a head-to-head comparator trial.

Van Naarden and Hyman acknowledged that these trials amount to a risky proposition, as researchers dont really know what theyre going to find. But theyd rather answer some of the pressing questions than go for an easy win, he said.

Its a riskier clinical trial portfolio, so you could lose some of these clinical trials and still have a really important drug, Hyman said. LOXO-305 is being compared to drugs that still do pretty well for patients.

See the original post here:

#ASH20 UPDATED: Loxo and Eli Lilly show off PhI/II data for their BTK inhibitor in two blood cancers - Endpoints News