Now that Alcon is officially off on its own, what is Novartis’ remaining eye medicine business looking at next? According to Nikos Tripodis, Novartis Ophthalmology’s worldwide franchise head, it's focusing on some cutting-edge innovations outlined by CEO Vas Narasimhan.
The business has a trio of top priorities, Tripodis said in an email interview. Bringing potential blockbuster brolucizumab to a successful launch in wet age-related macular degeneration, for one thing. Expanding in gene therapy, as spearheaded by the Luxturna treatment Novartis licensed from Spark Therapeutics, for another. And finally, exploring digital solutions in eye care—and possibly some M&A movements there.
Anyone who follows Novartis will notice that the two-pronged strategy—novel treatment platforms and a digital push—are an exact reflection of Narasimhan’s broader vision for the company.
AMD challenger brolucizumab
First up, the near-term focus is definitely brolucizumab, a potential rival to Bayer and Regeneron’s Eylea. Novartis paid up for a priority review voucher to speed FDA review and prep for a launch in 2019, and the company is already staffing up on sales reps in key regions, Tripodis said. In a February report, Evaluate Pharma projected the drug could reach sales of $1.38 billion by 2024.
The long-acting VEGF drug matched Eylea in best-corrected visual acuity (BCVA), the primary endpoint in two phase 3 trials dubbed Harrier and Hawk. And brolucizumab hit that mark when more than half of trial patients were dosed every quarter. Eylea is also approved in a 12-week dosing formulation, thanks to an FDA about-face last August.
When the data were unveiled in mid-2017, analysts at Jefferies described the Novartis med's dosing schedule as “a significant differentiator and competitive advantage.”
Brolucizumab also beat Eylea in some secondary endpoints, having consistently dried retinal fluid and reduced central subfield thickness (CST) over two years. But not all industry watchers are impressed; some argued that those markers aren't that important for wet AMD, otherwise known as neovascular AMD (nAMD). Tripodis disagrees.
“In nAMD, retinal fluid is a key marker of disease activity used by physicians to determine injection frequency in clinical practice,” he told FiercePharma. “An increase in CST in nAMD is an important measure of abnormal fluid accumulation and edema and may be associated with reduced vision.”
Novartis is counting on brolucizumab to expand its ophthalmology pharma portfolio, which now comprises more than 70 brands across many indications. And the franchise, which ranks as Novartis' second-largest in innovative medicines, does need help. Its $4.56 billion in 2018 sales amounted to a 2% decline from 2017 levels, thanks to stepped up U.S. competition for its travoprost products for glaucoma patients and generic rivals in Europe.
Lucentis, the Roche nAMD drug Novartis markets outside the U.S., offered the lion’s share of that revenue, with sales of $2.05 billion. But should Novartis be concerned of potential cannibalism after brolucizumab?
“We will manage both products as we always do when we have more than one product in an indication,” Tripodis said. Besides, as he pointed out, Novartis’ head-to-head clinical trials against Eylea already indicated brolucizumab’s marketing rival.
Novartis’ eye therapy pipeline looks relatively thin compared to its immunology and oncology programs, where the Swiss drugmaker is enjoying rapid growth. Besides additional late-stage trials in diabetic macular edema and retinal vein occlusion for brolucizumab, there are also ECF843, a recombinant form of human lubricin Novartis licensed from Lubris, and UNR844, a potentially first-in-class topical treatment in phase 2 development for presbyopia.
In terms of early-stage research, Tripodis said the Novartis Institutes for BioMedical Research (NIBR) is conducting research in glaucoma and AMD, and it’s conducting first-in-human study of CPK850, which is a human RLBP1 gene carried by an AAV vector intended for retinitis pigmentosa.
Narasimhan has specifically highlighted gene and cell therapies as growth targets, and ophthalmology could be considered a frontline effort there. The drugmaker started its gene therapy endeavor by licensing Spark Therapeutics’ Luxturna, the first-ever FDA-approved gene therapy for an inherited rare eye disease.
“Through our heritage in ophthalmology and our investment in accelerating gene therapy, Luxturna is bridging the gap between two very exciting areas of science that we believe is just the beginning of things to come in this space,” Tripodis said.
Luxturna, however, has been off to a slow start in the U.S. With an EU nod last November, Tripodis said Novartis will work with physicians to improve diagnosis and treatment at specialized eye centers and will bring the therapy to patients as quickly as possible after reimbursement decisions are made this year and next. Novartis expects Germany to be the first to launch the drug in Europe, Tripodis said.
Novartis isn’t alone in gene therapy for eye disorders. Among the other companies testing nAMD therapies are Sanofi and Oxford Biomedica, which happens to be one of Novartis’ partners in a separate cell therapy effort. But Sanofi and Oxford’s ophthalmic therapies don’t deliver functional genes but rather genes that express therapeutics.
Narasimhan, in a recent interview with Bloomberg, said he plans to spend some $10 billion a year on acquisitions and will continue to look at “bolt-on M&A” to consolidate its lead in gene therapy and other advanced therapy platforms.
In fact, as Tripodis indicated without providing any details, the company is indeed “actively evaluating” collaborations and M&A opportunities for several potential digital therapeutics in the ophthalmic field.
Under Narasimhan, Novartis has put an emphasis on digital. “Digital technologies and diagnostics can play a role in improving eye health, providing solutions from improving clinical trials to training doctors, improving compliance and even creating ‘digital therapeutics’ where the digital solution itself is part of the medicine,” Tripodis said.
On that front, Novartis in April 2018 launched the FocalView app to aid remote ophthalmic clinical trials. The app enables patients to upload self-reported assessments of visual acuity and contrast sensitivity, providing researchers with real-world patient experiences on a regular basis. The company is exploring “bringing vision testing to the palm of patients’ hands by exploring a visual acuity test to help measure near vision, with clinical trial testing set to start in Q2 this year,” Tripodis said.
Editor's Note: This story has been updated to show that Eylea is also approved for a 12-week dosing schedule.