Despite Wall Street's not-so-positive view of data from Regeneron Pharmaceuticals Inc.'s Phase II trial of its interleukin-1 Trap product in rheumatoid arthritis, the company believes the 200-patient trial demonstrates enough biological effect to forge ahead.
Regeneron's stock (NASDAQ:REGN) Tuesday fell $3.81, or 20.7 percent, to close at $14.59.
Of the negative response, George Yancopoulos, Regeneron's chief scientific officer, told BioWorld Today the problem might be that the data are being viewed from a formulaic perspective.
"I think one has to look at the totality of the data and the totality of the results," he said. "I think in the long run, leaders in the field and sophisticated individuals will see that the data is very consistent and, we think, very positive."
The trial missed its primary endpoint of ACR 20 (American College of Rheumatology criteria for improvement) responses. However, patients given 100 mg of IL-1 Trap did show an increase in the proportion of ACR 20 responses (46 percent vs. 30.9 percent for the placebo group, p=0.11).
Indeed, Mike King, managing director with Banc of America Securities in New York, told BioWorld Today the Phase II demonstrates more activity than the stock would indicate.
"I think people are focusing kind of slavishly to the statement that the study didn't achieve its primary endpoint with statistical significance, but this definitely is not a zero," he said. "The drug does show activity, and they didn't miss the primary endpoint by that much - 0.05 is not that far away from 0.11."
The consensus on The Street, though, is that the drug will be delayed due to the trial's failure to achieve the optimal dose level.
King agreed with that statement, saying the drug could lag by six months while the company possibly conducts another trial for the dosing. As for the next step, Yancopoulos said Regeneron and partner, Novartis AG, of Basel, Switzerland, have yet to make that decision.
"At this point, this data is all relatively new and we have decided obviously to move forward, but the exact design, size and phase of the next study remains to be determined," he said. "We are considering everything from a larger Phase II study that includes a higher-dose group - because it looks from this study that we didn't hit the top of the dose-response curve - to a Phase III study, which would include a higher-dose group as well."
IL-1 Trap was discovered by Regeneron, of Tarrytown, N.Y., and is being developed with Novartis in a deal potentially worth $350 million to Regeneron. Novartis paid Regeneron $75 million on signing the agreement and on April 1 took over financial responsibility for development, Charles Poole, Regeneron's vice president of investor relations, told BioWorld Today. (See BioWorld Today, March 31, 2003.)
IL-1 Trap blocks IL-1, which regulates immune and inflammatory responses by attaching to cell-surface receptors in the immune system. It "traps" target cytokines in the bloodstream before they can attach.
The multicenter Phase II was a randomized, placebo-controlled, double-blind study in people with active RA who have had an inadequate response to at least one disease-modifying antirheumatic drug. Patients in the treatment arm received 25-mg, 50-mg or 100-mg weekly subcutaneous injections.
The 100-mg group showed improvements in secondary endpoints. Data from the secondary endpoints included an increase in the average ACR-N Score, 24.1 percent vs. 13.5 percent, (p=0.02); an increase in the proportion of ACR 50 responses, 20 percent vs. 9.1 percent, (p=0.11); and an increase in the proportion of ACR 70 responses, 12 percent vs. 3.6 percent, (p=0.11). That dose also demonstrated a faster time of onset of ACR 20 responses (median time to onset), 36 days vs. 77 days, (=0.03); and a decrease in C-reactive protein, a systemic marker of inflammation, -1.36 vs. +0.07 (p=0.004).
Yancopoulos said the data show clear clinical activity and drug effect in the primary and all secondary endpoints examined. He added that the "p" value is dependent on the size of the study, and had this Phase II been larger, it likely would have ended with statistical significance.
"It's a matter of looking at all the data in its totality and seeing that there's a rather consistent picture that shows a rather impressive drug effect combined with a very good tolerability and safety profile, and a low immunogenicity, which gets us pretty excited about moving forward here," he said.