Just a few months after Regeneron $REGN and its partners at Teva $TEVA were forced to drop the two high-dose arms of their Phase III study of the NGF pain med fasinumab, researchers say the remaining two low-dose arms cleared a late-stage hurdle, opening the way to more Phase III trials as they hunt an elusive approval for a brand new class of pain therapies.
This one isn’t easy.
Just a few months ago the top team at Regeneron uneasily acknowledged in a Q1 call with analysts that the independent monitoring board had told them to shelve the two highest doses in the study, citing concerns about the risk/benefit profile. Once a darling in Big Pharma circles, NGF drugs were tied to severe adverse events that forced a lull in trial work from 2012 to 2015, until researchers could persuade regulators that they could test it without threatening patients. And Regeneron and Teva have already endured a clinical hold for their program, which came right after Teva paid $250 million to partner on the therapy.
The recent setback on fasinumab stirred some serious concerns that those old problems had once again become an issue — while a rival late-stage program at Pfizer $PFE and Eli Lilly $LLY for tanezumab has also stirred lingering concerns. Just a month ago the partners said that their drug had also cleared a Phase III, but noted that the rate of “rapidly progressive osteoarthritis was observed in tanezumab-treated patients at a frequency of less than 1.5%, and was not observed in the placebo arm.”
“(T)his is a high-risk, high-reward program as we’ve described in the past,” R&D chief George Yancopoulos told analysts in May. “It’s pretty well-demonstrated that the molecule has activity, but it also has certain side effects. It’s not osteonecrosis, it’s more defined as rapid progression of the osteoarthritis in some patients. And this is something that obviously has been seen with this class and with our molecule before. And so what the independent data monitoring committee did was they obviously took an analysis to look at the benefit and the risk that is the therapeutic benefit compared to their analysis of the risk coming from these rapidly progressive osteoarthritis events and they decided that we should terminate the upper two doses and continue with the two lower doses.”
Those two lower doses came through, though. In their release Thursday the partners noted highly significant p values for the 1 mg dose every 4 and 8 weeks for both pain and physical function. They added that the drug also hit goals for “key” secondary endpoints. Using radiographic monitoring of their joints, researchers pegged the placebo-adjusted rate of adjudicated arthropathies at “approximately 2%.”
The majority of patients suffered from osteoarthritis of the knee.
That safety issue, says Evercore ISI analyst Uber Raffat, pretty much eliminated any perceived value in this drug. And Raffat remains on high alert regarding the safety profile.
He noted Thursday morning:
As it stands now, the placebo-adjusted increase in RPOA is 2% (again, this is the INCREASE – we don’t know the absolute rates in this trial). We did NOT get a clear statement in PR for whether there has been a Type 2 RPOA (rapid progressive OA type).
If these NGF drugs can get through Phase III intact, some analysts still believe that there’s a big market waiting for a nonopioid pain med. But there’s still a long way to go in Phase III, with this current readout centered on a preliminary sub-study. They’re recruiting patients for three more Phase III studies while this trial continues on, with a 52-week mark ahead and a further 72-week safety assessment.
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