With the two-day meeting of the FDA's Arthritis Advisory Committee (adcom) scheduled to convene next week to address biologics license applications for two biosimilar candidates, companies jockeyed for position by presenting data on related indications at Psoriasis 2016, the 5th Congress of the Psoriasis International Network in Paris.

Abbvie Inc., which has made no secret of its intent to defend its $14 billion-a-year legacy drug, Humira (adalimumab), presented findings from a phase III study of adult patients with moderate to severe psoriasis showing that 46.6 percent of those treated with the drug achieved improvement of at least 75 percent in modified Nail Psoriasis Severity Index at week 26 compared to 3.4 percent for placebo, meeting the primary endpoint.

Fingernail psoriasis isn't explicitly disclosed as part of Amgen Inc.'s presentation on ABP 501, its biosimilar version of adalimumab, on Tuesday's adcom agenda. However, Abbvie maintained that the condition occurs in up to 55 percent of people living with psoriasis and up to 70 percent of people living with psoriatic arthritis – one of seven proposed indications for the biosimilar, along with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis, Crohn's disease, ulcerative colitis and plaque psoriasis.

Abbvie also reported at Psoriasis 2016 that, at week 26, 48.9 percent of patients treated with Humira in the fingernail psoriasis study achieved Physician's Global Assessment-fingernail-psoriasis of 0 (clear) or 1 (minimal) with at least a 2-point improvement from baseline, compared to 6.9 percent for placebo (p<0.001), meeting the co-primary endpoint.

No new safety signals were identified with dosing of Humira every other week through 26 weeks. Adverse events (AEs) were reported by 56.9 percent of patients treated with Humira and 55.6 percent of those who received placebo. Serious AEs were reported by 7.3 percent and 4.6 percent, respectively, including serious infections in 3.7 percent of those treated with Humira compared to 1.9 percent on placebo.

Abbvie reported additional Humira data at the meeting related to patient-reported outcomes of psoriasis symptoms, long-term responders and safety in pediatric patients.

Meanwhile, Sandoz Inc., a unit of Novartis AG, of Basel, Switzerland, reported that the phase III EGALITY trial of its biosimilar candidate, GP-2015, hit its primary endpoint by achieving equivalence in Psoriasis Area and Severity Index (PASI) 75 response rates at week 12, compared to the originator product, Enbrel (etanercept, Amgen Inc.), in patients with moderate to severe chronic plaque-type psoriasis. Chronic moderate to severe plaque psoriasis is one of four indications for which Sandoz will plead the case for GP-2015 during the adcom's Wednesday session. The other proposed indications are RA, JIA and psoriatic arthritis.

Additional data from the study confirmed similarity between the biosimilar etanercept candidate and the reference drug in terms of safety and immunogenicity. The incidence of AEs at week 12 was comparable, according to Sandoz.

The randomized, double-blind EGALITY trial enrolled 531 patients across 74 dermatology clinics in 11 European countries and South Africa, comparing the efficacy and safety of the Sandoz biosimilar with Enbrel. Patients received multiple treatment switches, alternating between the biosimilar and the originator product. In addition to the primary endpoint of PASI 75 response rate, key secondary endpoints at week 12 included percentage change from baseline in PASI, clinical safety and immunogenicity.

The Psoriasis 2016 data dumps seem timed to position drugs on both sides of the U.S. biosimilars battle. A spokesman for Sandoz confirmed the EGALITY study will be part of the adcom data package but said the company had no further comment. Officials from Abbvie and Amgen, which presented several posters at Psoriasis 2016, did not respond to BioWorld.

LITIGATION DRIVING U.S. BIOSIMILARS LAUNCH TIMING

Amgen's Neupogen (filgrastim) was the first biologic to face a biosimilar in the U.S. – Zarxio (filgrastim-sndz), also from Sandoz. Amgen, of Thousand Oaks, Calif., responded with its own biosimilar pipeline, which now numbers six disclosed candidates targeting blockbuster biologics made by other biopharmas. (See BioWorld Today, March 9, 2015.)

But the first line of defense for Amgen, and for other biologics sponsors, is to delay the inevitable as long as possible. To that end, innovators have extended the intellectual property for each biologic by developing bigger patent portfolios. (See BioWorld Today, April 27, 2016.)

Abbvie, of North Chicago, has amassed more than 60 patents for Humira, including two product patents, 11 use patents, 26 formulation patents, nine process patents and eight patents on delivery devices, according to Thomson Reuters Cortellis. While several patents expired earlier this year, certain method and manufacturing patents won't expire until 2033, and at least one extends into 2034. (See BioWorld Today, April 29, 2016.)

The FDA also has shown willingness to carve out indications, as it did when approving Inflectra, developed by South Korea's Celltrion Inc. as a biosimilar to Janssen Biotech Inc.'s Remicade (infliximab) and licensed to Pfizer Inc. in the U.S. At the time of Inflectra's approval, Remicade still had pediatric exclusivity on one indication. (See BioWorld Today, April 6, 2016.)

And when Zarxio was approved, only the existing Neupogen indications were extrapolated. (See BioWorld Today, Sept. 4, 2015.)

As companies go stride for stride in the biosimilars contest, analysts seem convinced that patent power will dominate outcomes, at least in the near term. In an email late last month following his meeting with Abbvie officials, Evercore ISI analyst Mark Schoenebaum reported that "litigation, not the [inter partes review] process, will determine whether or not biosimilars come to market." He said that Abbvie intends to file a lawsuit within several months against Amgen that could "hypothetically assert 20-30 patents with 200-300 claims" against Amgen, using patents previously agreed upon by the companies as part of the adalimumab patent dance. Considering the amount of time needed for litigation to play out, he forecast late 2019 or early 2020 as "the earliest one would expect Humira biosimilars."

Moreover, Abbvie needs to defend only one patent with a single claim to block a launch, according to Schoenebaum, while Amgen must "take down every patent and every claim" to win.

"Launching at risk and subsequently infringing could lead to a multibillion-dollar settlement (and ABBV would file a preliminary injunction to stop an at-risk launch)," he added.

During their meeting, Abbvie officials reiterated prior guidance of 15 percent to 18 percent erosion in Humira EU revenues over the 2019-2020 time period, Schoenebaum said, though they acknowledged the actual revenue impact will be closer to 30 percent "because Humira would have otherwise grown during that time." Abbvie suggested Humira erosion curves "would be somewhat similar in the U.S.," he said.

In a broad analysis of upcoming pharmaceuticals catalysts released this week, Credit Suisse analyst Vamil Divan characterized the biosimilar "threat" as a headwind for the industry moving into the second half of the year.

He predicted that Humira will continue to drive strong near-term growth for Abbvie but raised concerns around the "timing and magnitude of impact" from biosimilars.

In the end, however, he concurred with Schoenebaum's assessment.

"Our channel checks continue to suggest that prescribing in these areas tends to be sticky, and it could be a while until oral competitors establish themselves," Divan wrote.

"There remain significant unknowns in the biosimilar development space, and ABBV's patent defenses could be underappreciated. Even with accommodative FDA and legal steps, 2019-2020 [is] likely the earliest we see biosimilar entry in the U.S.," he noted.