DUBLIN Ablynx NV's anti-interleukin-6-receptor (IL-6R) inhibitor, vobarilizumab (ALX-0061), demonstrated equivalent efficacy to the incumbent, Actemra (tocilizumab), in a phase IIb monotherapy trial in rheumatoid arthritis (RA). Some investors liked what they saw, pushing up the company's stock by as much as 17 percent early Thursday.
The key question is whether licensing partner Abbvie Inc. shares their enthusiasm, as Ablynx has a €75 million (US$83.2 million) payment riding on an option to the molecule held by the North Chicago firm. It won't get an answer until later this year, after a readout from a second phase IIb trial in RA, which pairs vobarilizumab with methotrexate.
The original 2013 deal between Ablynx and Abbvie is worth up to $845 million, including $175 million of which was paid up front. In the present trial, participants (n=251) were assigned to receive either vobarilizumab, in one of three dose regimens 150 mg every four weeks (Q4W), 150 mg Q2W, or 225 mg Q2W or Actemra, which was administered weekly (n=60) or every two weeks (n=4).
After 12 weeks, all three vobarilizumab dose regimens tested were on a par with tocilizumab. Those on the lowest dose (n=62) attained ACR20, ACR50 and ACR70 response rates of 73 percent, 44 percent and 16 percent, respectively. For the mid-dose regimen (n=62), the ACR20, ACR50 and ACR70 response rates were 77 percent, 37 percent and 24 percent, respectively, and for the high-dose regimen (n=63), they were 81 percent, 49 percent and 21 percent, respectively.
The respective response rates for those on Actemra were 78 percent, 45 percent and 23 percent.
"This is probably about as good as we could have expected," Edwin Moses, CEO of Ghent, Belgium-based Ablynx, told BioWorld Today. "When we look out at the world, we don't see anything better than this."
Given the disparities in dosing frequency, those on vobarilizumab had received just three or six doses during the study period, whereas the vast majority of those on Actemra received 12 doses of drug. The high-dose regimen of vobarilizumab, moreover, appeared to show a clear advantage over Actemra on another efficacy measure, disease activity score 28 C-reactive protein (DAS28CRP). Forty-one percent of those on vobarilizumab 225 mg Q2W achieved remission defined as a score of less than 2.6 whereas just 27 percent of those on Actemra did.
Vobarilizumab also appeared to have a better safety profile. The discontinuation rate across all vobarilizumab dose groups was 2.1 percent, while it was 6.3 percent for those on tocilizumab. Serious treatment-related adverse events were also lower among those on vobarilizumab 0.5 percent vs. 3.1 percent for those on Actemra.
Nevertheless, there are caveats attached to the data. "It's not powered to show a statistical difference. We have to be careful in interpreting this," Moses said. Moreover, the Actemra arm of the study was unblinded patients knew they were receiving that drug.
So whether all that adds up to best in class Ablynx's design goal for the 26 kilodalton bispecific nanobody is moot for now. "We believe less frequent dosing, higher remission rates and fewer serious adverse event are encouraging. However, it remains uncertain if '0061 is a 'must have' for partner Abbvie, with an opt-in decision likely in the fourth quarter," Jefferies analyst Peter Welford wrote in a briefing note.
'HUGE DIFFERENCE IN THIS SCENARIO'
The uncertainty stems from Abbvie's readiness to confound expectations, as well as its possession of a rival asset, its internally developed JAK1 inhibitor ABT-494, which is now in phase III trials in RA. Last year, Abbvie walked away from an option to take forward another JAK1 inhibitor, Galapagos NV's filgotinib, thereby avoiding a $200 million milestone payment and possibly up to $1 billion more to come. (See BioWorld Today, Sept. 28, 2015.)
However, that was then, and this is now the present situation is not exactly the same. "They don't have an IL-6R inhibitor. I think that is a huge difference in this scenario," Moses said. "Were they not to go forward with this, our intention would be to take it into phase III and seek another partner." Foster City, Calif.-based Gilead Sciences Inc. would be an obvious choice, having swooped on filgotinib in a mammoth $2.075 billion deal shortly after Abbvie passed on that drug. (See BioWorld Today, Dec. 18, 2015.)
Ablynx has been down this road before. Several years ago, Pfizer, Inc., of New York, exited an alliance in RA based on ozoralizumab (ATN-103), a TNF-alpha inhibitor. It later found new regional partners in Asia, Eddingpharm International Holdings Ltd., of Hong Kong, and Tokyo-based Taisho Pharmaceutical Co. Ltd. (See BioWorld Today, Nov. 7, 2011.)
The picture will become a little clearer in the coming weeks data from the phase IIb combination trial, in 345 patients, are expected in August. A phase II study in systemic lupus erythematosus is due to read out in 2018.
Ablynx's stock (Brussels:ABLX) shed some of its early gains to close Thursday at €12.95, up 12 percent.