That effort by Regeneron Pharmaceuticals Inc. to get a toehold in the potentially lucrative respiratory syncytial virus (RSV) market with a candidate that had FDA fast track status? It's kaput, after the Tarrytown, N.Y.-based company said the phase III study of suptavumab (previously REGN-2222) missed the primary endpoint of preventing medically attended RSV infections in infants. Regeneron said suptavumab showed signs of efficacy in a subgroup of patients and that adverse events (AEs) were generally balanced between the study drug and placebo.

The company plans to report details at an undisclosed medical meeting. In the meantime, Regeneron is shelving the antibody, an RSV protein F inhibitor.

The double-blind, placebo-controlled NURSERY study enrolled 1,149 healthy pre-term infants across sites in 20 countries, according to Cortellis Clinical Trials Intelligence. Pre-term infants in the study had a gestational age of less than 36 weeks and were 6 months old or younger at the beginning of the study.

The infants were randomized in a 1:1:1 ratio to suptavumab 30 mg/kg administered as a single dose, suptavumab 30 mg/kg administered as two doses eight weeks apart or placebo. Assessment of the primary endpoint occurred through day 150 of treatment. Patients were considered medically attended if they required hospitalization and/or sought medical care for a centrally adjudicated RSV infection.

The NURSERY trial also evaluated the co-primary endpoint of serum concentration of suptavumab over time, measured through day 150, according to Cortellis. In addition to safety measures of treatment-emergent AEs and the presence of anti-REGN-2222 antibodies, secondary endpoints included the proportion of subjects with RSV-confirmed hospitalization, emergency room, urgent care or pediatric clinic visits for upper or lower respiratory infection as well as pharmacokinetic parameters.

Despite disappointment about the suptavumab results, the company didn't miss a beat, as George Yancopoulos, president and chief scientific officer, pointed to Regeneron's "robust pipeline across many serious diseases" and "important data readouts from other programs in the coming weeks and months." Investors also seemed unperturbed by the setback. The company's shares (NASDAQ:REGN) gained $7.95, to close at $475.39 on Monday.

Through a spokeswoman, Regeneron declined additional comment.

'This asset is not a big lever'

Yancopoulos barely referenced suptavumab during Regeneron's second quarter earnings call. Analysts asked no questions, although Leerink analyst Geoffrey Porges gauged prospects for success of the phase III program in RSV at 65 percent, calling the pivotal trial one of Regeneron's "important data readouts for 2017."

Following the company's disclosure of the top-line results on Monday, J.P. Morgan's Cory Kasimov surmised that "this asset is not a big lever in Street models [it's not in ours]," but pointed out that "it is a phase III product the company spoke frequently about for a potentially meaningful, blockbuster indication."

Still, Kasimov also looked ahead, adding, "The potential of REGN's commercialized products and key pipeline assets/indications are largely appreciated by investors and reflected in its current valuation. To that end, we consider today's development an incremental disappointment as we await the emergence of new, potentially impactful earlier-stage growth drivers."

In her company update, Morningstar's Karen Andersen lowered the fair value estimate for Regeneron's shares to $500 from $520 following the decision on suptavumab, based on previously assumed probability-adjusted peak sales of approximately $500 million. But Andersen also was focused elsewhere, writing, "The majority of Regeneron's fair value estimate is driven by our expectations for the Eylea and Praluent franchises. We think Eylea could see worldwide peak sales of more than $8 billion should it continue growing in international markets, despite slower U.S. growth. We think Praluent can achieve sales of about $3 billion and sales acceleration would follow expected positive outcomes studies in 2018."

Regeneron's long-time partner Sanofi SA, of Paris, previously was developing suptavumab in collaboration but opted out of the project in February 2015, according to Cortellis, when the big pharma re-prioritized following the ouster of former CEO Chris Viehbacher. Even then, all eyes were on Eylea (aflibercept) and the race to market with Amgen Inc. for the first proprotein convertase subtilisin/kexin type 9, or PCSK9, inhibitor to treat high cholesterol. (See BioWorld Today, Aug. 1, 2014, Aug. 6, 2014, and Oct. 30, 2014.)

Earlier this month, Regeneron disclosed that its antibody discovery agreement with Sanofi will end at year-end, in accordance with terms of the deal, without an extension. However, an antibody licensing collaboration agreement, immuno-oncology (I-O) discovery and development pact and I-O licensing collaboration will continue unaffected.

As Regeneron takes suptavumab out of the mix, RSV again becomes a wide open field. Novavax Inc. also saw its RSV-F vaccine candidate in older adults fall apart last year in phase III. Other efforts, such as Alnylam Pharmaceuticals Inc.'s ALN-RSV01, were halted following misses in mid-stage development. (See BioWorld Today, May 31, 2012, and Sept. 19, 2016.)

But the pipeline is ample, with 16 candidates in phase II development, a dozen in phase I and more than 60 agents in discovery to treat RSV in infants or older adults. Some of the phase II contenders include lumicitabine (AL-8176), which Janssen Pharmaceuticals Inc. is advancing following parent Johnson & Johnson's $1.75 billion acquisition of Alios Biopharma Inc., which developed the oral nucleoside analogue; Shanghai-based Ark Biosciences Inc.'s AK-0529, licensed from Roche AG; Aviragen Therapeutics Inc. candidate, BTA-585, which missed the primary endpoint of reducing viral load but showed strong safety in a phase IIa trial; and Astrazeneca plc's MEDI-8897, a next-generation successor to its Synagis (palivizumab) franchise partnered with Sanofi to prevent RSV infection in at-risk infants. (See BioWorld Today, Oct. 1, 2014, Sept. 25, 2015, Feb. 3, 2017, and March 6, 2017.)