Shire PLC CEO Flemming Ornskov will call on his background in ophthalmology drugs to help the specialty pharma launch a fourth business unit centered on the lucrative eye indications. The new business focus will revolve around Shire’s revived late-stage dry-eye drug lifitegrast.

Lifitegrast, which has yielded mixed results across two Phase III studies and largely been discounted by analysts as a lost cause, will be filed for regulatory approval in the first quarter of 2015, Shire announced May 16. The move to bring the candidate forward followed a mid-May meeting with FDA that gave the drug a clearer regulatory path.

“This surprise news suggests that lifitegrast could yet enter the circa $1 billion (and growing) market pioneered by Allergan’s only modestly effective drug Restasis. We currently carry zero sales in our model (and consensus has under $200 million by 2018) but have previously estimated that lifitegrast could represent a $600 million to $1 billion opportunity,” Deutsche Bank analyst Mark Clark wrote in a May 19 note to investors.

The drug, which inhibits T-cell inflammation by blocking two proteins – lymphocyte function-associated antigen (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) – showed promising results in Phase II, but then produced mixed results in the Phase III OPUS-1 and OPUS-2 studies.

The OPUS-1 study met one of two co-primary endpoints, reducing signs of dry eye, but did not meet a second co-primary endpoint, reducing symptoms of dry eye. The OPUS-2 study met the co-primary endpoint of reducing symptoms of dry eye, but failed to reduce the signs of dry eye, such as corneal scarring.

“Given the contradictory OPUS-1 and -2 Phase III results, we (and a number of other banks) removed lifitegrast from our models, although Shire continued to express optimism that it would find a regulatory path forward. According to EvaluatePharma, the consensus 2018 estimated sales forecast for lifitegrast is just $171 million while that for Restasis is $1.2 billion,” added Clark.

The first quarter NDA filing will be based on the totality of the Phase II and III data, the company said. It currently is preparing chemistry and manufacturing work for the submission and is evaluating the need for additional clinical information to support the U.S. filing, as well as filings in the EU and Japan.

“If FDA had specifically asked for an additional pivotal study, potential launch would be in 2017/2018. Management is evaluating the possibility of conducting additional studies to enhance the NDA and indicates that data from new studies (if conducted) will be submitted as a supplement. As such, there is now a path for commercialization as early as 2016. If Shire conducts another study, the inference is it will not be another pivotal Phase III,” wrote Jefferies analyst David Steinberg.

Lifitegrast was the prime driver of Shire’s March 2013 acquisition of SARcode Bioscience Inc. Shire paid $160 million upfront for the company and agreed to undisclosed milestones Also see "New Shire CEO Has Big Ophthalmology Plans; SARcode Sets The Stage" - Pink Sheet, 25 March, 2013..

Currently, there are no drugs approved for treating the signs and symptoms of dry-eye disease. The only drug on the market is Allergan Inc.’s Restasis (cyclosporine), which is approved for increasing tear production in patients with dry-eye disease.

Restasis posted sales of $940 million in 2013 and is expected to exceed $1 billion this year. But it has a number of shortcomings in this indication, including slow onset to action and modest efficacy. “[Restasis] was rejected several times by the FDA before finally gaining approval based on a pooled analysis of all trials. In our view, this commercial success reflects a combination of its position as the ‘only game in town’ and the high unmet need in dry eye disease,” noted Clark.

New Focus In Ophthalmology

Shire’s move into the ophthalmology space matches the background of its relatively new CEO, Ornskov. Prior to joining Shire in 2013, he worked at Bayer AG, where he helped commercialize the macular degeneration asset Eylea; he also previously worked at eye specialist Bausch & Lomb Inc. as global president of pharmaceuticals and OTC and previously headed up Novartis AG’s ophthalmology business.

Ornskov took to reorganizing Shire’s overall structure when he came in, flattening the management structure and doing away with flailing businesses, like the regenerative medicines unit ([A#14130502006] and Also see "Shire Sheds Dermagraft; Exits Regenerative Medicine" - Pink Sheet, 17 January, 2014.).

The Ophthalmology Business Unit will be led by Robert Dempsey, while Reza Haque will serve as Therapeutic Area Head for Ophthalmology, both hired from Bausch & Lomb.

Aside from lifitegrast, the unit has another compound in the pipeline. SHP607 is currently in Phase II for retinopathy of prematurity (ROP), a disease that affects premature babies. This compound was added through the March 2013 acquisition of Premacure AB.

Shire told “The Pink Sheet” DAILY it intends to flesh out the business unit with complementary compounds that serve unmet medical needs.

Ophthalmology is becoming a hot therapeutic area as the general population ages and experiences more age-related eye problems; this area is of particular interest for specialty pharma companies that want to target niche areas of the population. The focus is being spurred by the success of drugs such as Eylea (aflibercept) and Lucentis (ranibizumab) Also see "Start-Ups, With An Eye On Success In Wet AMD, Tackle The Dry Form" - Pink Sheet, 25 June, 2012..

Shire Course Corrects Lifitegrast And Eyes Ophthalmology Prospects

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