Spurned by Teva, checkpoint immunotherapy combo looks promising in PhII

Former Teva CEO Jeremy Levin

Back in January, Jeremy Levin--then riding high as CEO of Teva Pharmaceutical Industries--didn't think much of the company's program for an immune checkpoint receptor drug dubbed CT-011, or pidilizumab. He had already had a chance to tell a reporter that with top outfits like Bristol-Myers Squibb ($BMY), where Levin had gained a reputation as a dealmaker, pushing hard on rival programs, it would be "very hard to be successful in this area."

So it was no great surprise when he dumped the drug at the end of January, taking a $109 million writeoff to get out of its longtime deal with Israel's CureTech.

Since then, much has changed. Levin is out at Teva ($TEVA) after a brutal showdown over reorganizing the company, and pidiluzumab--designed to block the PD-1 checkpoint receptor and unleash an immune system attack on cancer--just posted promising results from a small Phase II study on relapsed follicular lymphoma that matched it with Rituxan. And those checkpoint receptor drugs that Levin had ceded to the leaders in the field have emerged as one of the hottest R&D arenas in the industry, which may help open a second chapter in the story of pidilizumab.

After a little more than 15 months of therapy, 19 of the 29 patients--or 66%--taking the combo had a complete or partial response, says Sattva Neelapu, the lead investigator at the University of Texas MD Anderson Cancer Center. Most of that group, 15 patients--or 52%--had a complete response, says Neelapu, an associate professor of lymphoma/myeloma. And the drug produced none of the grade 3 or 4 adverse events that raise safety concerns, triggering only "mild effects" among a group of patients with a median age of 60.

"Rituximab treatment alone usually achieves a 40 percent overall response rate and about 11 percent complete responses," Neelapu said in a statement. "And the side effect profile of the combination is about the same as rituximab alone. Adding pidilizumab greatly improves responses so far at little cost in additional side effects."

Since Levin decided to dump the company's immunotherapy program, checkpoint receptor drugs have become all the rage in the industry. Bristol-Myers Squibb, Merck and Roche have seized the lead, pushing along some of the most closely watched development programs in the industry. Targeting the PD-1 or complementary PD-L1 receptor unleashes a T-cell attack on cancer cells, essentially deactivating a cloaking mechanism that has prevented an immune response. At Bristol-Myers Squibb investigators have been racing ahead with nivolumab, combining it with Yervoy against melanoma, while Merck ($MRK) hurries along MK-3475 and Roche ($RHHBY) focuses on its own PD-L1 program.

Behind them you'll find AstraZeneca ($AZN) and others looking at a wide variety of combination therapies and new strategies that are expected to quickly unfold as investigators put these programs on the fast track. Now, coming up from the back of the pack, comes a new contender with Phase II data.

- here's the release

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