With Baricitinib, Lilly Hopes To Succeed Where Pfizer Has Struggled

With data demonstrating superiority to Humira and likely lower pricing than anti-TNF drugs, baricitinib may be poised to make more of an impact than Pfizer has with its JAK inhibitor Xeljanz.

With regulatory filings now under review in the US, EU and Japan for baricitinib, an oral, selective JAK1/2 inhibitor, Eli Lilly & Co. sees a chance to position the drug in the competitive rheumatoid arthritis space after generic methotrexate therapy but before use of tumor necrosis factor inhibitors.

The Indianapolis pharma outlined its strategy for baricitinib, partnered with Incyte Corp., during an investor day presentation May 24 in New York (see related story, (Also see "Lilly Shows Off R&D Progress With A Pain Franchise Built On New Mechanisms" - Pink Sheet, 30 May, 2016.)). Senior Medical Director Bill Macias highlighted the drug's strong data package, derived from five Phase III trials, including data showing superiority to AbbVie Inc.'s Humira (adalimumab) on signs and symptoms of disease as well as patient-reported outcomes. Lilly had previously presented data from the RA-BEAM and RA-BEGIN studies showing superiority on PROs (Also see "Lilly Ready To Take Oral RA Drug Baricitinib To Finish Line" - Pink Sheet, 8 Nov, 2015.).

If approved, baricitinib will be the second Janus kinase inhibitor to reach the market in RA, following Pfizer Inc.'s Xeljanz (tofacitinib), which to date has been somewhat of a commercial disappointment. During the investor day presentation, Lilly execs extolled the drug’s advantages over Pfizer's Xeljanz, and analysts hope they will heed the lessons available from Pfizer's struggle in gaining acceptance of the first oral JAK inhibitor with payers and clinicians.

Lilly started out making sure to identify a once-daily dose, which the execs showed has no tolerability or safety concerns and to have structural benefits. Xeljanz entered the market with twice-daily dosing.

Another hurdle baricitinib will face, however, will be overcoming competition from the entrenched anti-TNF class, led by Humira. But analysts expect Lilly to vie for market share based on price, strong data and the convenience of a daily, oral tablet. Lilly declined to offer specifics about its potential pricing strategy for baricitinib, but VP-Medical Affairs Dave Kendall said the company sees several ways to differentiate in RA.

"The drug appears safe, and it's really quite an easy treatment for physicians to use once it's approved," he told the audience. "We are going to position this in front of biologic therapy. That will take different amounts of time, depending on the reimbursement and payer systems around the world. But we need to start with the clinical data … and where this drug is best used."

Kendall asserted that Lilly's broad-based Phase III program for baricitinib provided "a real world test," including investigation against Humira as an active comparator in RA-BEAM. Over the five-study program, the drug was used in a number of patients who had taken multiple biologics for RA, and while Lilly has not disclosed the specific data yet, Kendall said Lilly saw "really outstanding efficacy," including separation from the competition on the American College of Rheumatology 20 (ACR 20) score.

"As we think about the attributes and take advice from leading thought leaders on rheumatology, really the best place to ask for the business if you will, to position the drug, is in front of biologics," he said. "That doesn't mean we won't get broad use across the whole spectrum. However, and we have data to support that, I think in the early days of launch in particular because of step-therapy requirements, etc., we may see quite a bit of use there. Hopefully, clinicians can build on that experience and try it earlier as well."

Strategy For Targeting Refractory TNF Patients In US

In a May 25 note on the R&D day, Leerink Partners analyst Seamus Fernandez said Lilly's strategy seems to be focused on going after patients who are refractory to TNF inhibitors in the US. Internationally, the company expects a more level playing field because it will be less expensive than anti-TNF biologics, he wrote.

"Despite the drug's oral dosing and clinical profile warranting use in earlier lines of therapy, Lilly urged patience regarding the initial launch in the US," Fernandez said. "Due to the structuring of rebates, early adoption of baricitinib will likely occur predominantly in a TNF-refractory population. Outside of the US, it expects pre-TNF use to occur more quickly due to a more favorable reimbursement environment."

In another May 25 note, Credit Suisse analyst Vamil Divan called baricitinib "a likely blockbuster" that would have greater commercial impact in the RA space than Xeljanz. "We sense the company has learned from Pfizer's challenging launch of Xeljanz and will choose a lower price point for baricitinib, leading to fewer hurdles in getting patients on therapy and a potentially more rapid launch after regulatory approval early next year, while also allowing them to target patients both before and after anti-TNF therapy."

BMO Capital Markets' Alex Arfaei concurred with this optimistic outlook in a May 24 note, predicting that baricitinib would post peak sales of $1.7bn by 2024.

Although approved in 2012 for RA, Xeljanz has never built up much commercial momentum, leading Pfizer to scale back its overall development plans for the molecule (Also see "Xeljanz Development Plans Scaled Back By Pfizer" - Pink Sheet, 27 Oct, 2015.). It has abandoned plans to develop the drug in Crohn's disease, ankylosing spondylitis and possibly psoriasis, although Pfizer unveiled top-line Phase III data in psoriatic arthritis earlier in 2016. Lilly has baricitinib in Phase II studies in atopic dermatitis and systemic lupus erythematosus.

On May 3, Pfizer reported that Xeljanz posted global sales of $197m during the first quarter, including $175m in the US, up 98% year-over-year for domestic sales. In February, the pharma obtained FDA approval of an extended-release 11 mg formulation of tofacitinib, making it the first once-daily oral therapy for RA, potentially minimizing one area of differentiation for baricitinib.