Developers of FYB201 may be getting a leg up in the race for a Lucentis biosimilar with the publication of interim results that confirm the efficacy of the candidate for monthly treatment of neovascular age-related macular degeneration (nAMD), with plans to bring it to market in 2020.
However, a new generation of anti-VEGF agents that require less frequent dosing may be complicating the outlook for anti-VEGF biosimilars. Novartis has reported encouraging Phase III results of brolucizumab 12-week injections, and Roche/Genentech continues to collaborate on a form of Lucentis (ranibizumab) that requires less frequent dosing for nAMD, diabetic macular edema, and other retinal diseases.
Biosimilars are copycat versions of biological agents. Here’s an update on the race for anti-VEGF biosimilars as well as developments of the next generation of index anti-VEGF agents.
Formycon-bioeq Candidate Makes Progress
The latest move on the biosimilars front came early in May when Formycon AG of Germany and licensee Zurich-based bioeq IP AG disclosed the Phase III COLUMBUS-AMD trial had achieved its primary endpoint, showing FYB201 and Lucentis had comparable efficacy for improvement of best-corrected visual acuity after eight weeks. The confidence interval lies within the pre-defined equivalence limits, and the study has so far progressed without any safety and immunogenicity issues.
The trial involves treatment for a total of 48 weeks, and the last patient is expected to complete treatment by the end of June. The data from the Phase III study will be part of applications to the Food and Drug Administration and the European Medicines Agency. bioeq is responsible for the clinical Phase III study, and holds the exclusive global marketing rights for FYB201.
“Our aim is the approval and launch of FYB201 as the first biosimilar to Lucentis in the United States of America in 2020 and in the countries of the European Economic Area in 2022,” says Dr. Thiemo Schreiber, head of business development for bioeq.
Pfenex Candidate on Hold
Pfenex’s plans to develop the Lucentis biosimilar PF582 have been put on hold. In a corporate presentation early in May, Pfenex CEO Evert Schimmelpennink said the company is considering strategic partnerships to advance the program. BioPharma-Reporter.com quoted CFO Susan Knudson as saying in a call with stakeholders that the company had decided to pause development of PF582, along with the Neulasta biosimilar PF529. PF582 had been in Phase II trials. Pfenex announced in 2016 that it had regained full rights to PF582 after partner Pfizer had pulled back from the program.
South Korean Candidate in Phase III
Samsung Bioepis of South Korea last year received regulatory approval to begin a Phase III clinical trial of its Lucentis biosimilar, known as SB11, The Investor of Korea reported. Samsung Bioepis has a track record of getting biosimilars approved in Europe and the US. Its Renflexis (infliximab-abda), a biosimilar of Janssen’s Remicade, received FDA approval in April 2017.
Eylea Biosimilar Candidate
Another South Korea-based company, Alteogen, said in January that it would file an Investigational New Drug application with the FDA for ALT-L9, its biosimilar of Eylea (aflibercept, Regeneron). “We believe that our Eylea biosimilar will create higher market value than Lucentis biosimilar products as more patients opt for Eylea because it is more patient friendly due to a less-frequent dosing schedule,” an Alteogen official told The Investor of Korea. Eylea had $5.2 billion in global sales in 2016.
It’s All in the Timing
Meanwhile, Novartis has turned up the challenge to Lucentis and Eylea, and their monthly and bi-monthly dosing regimens, respectively. Novartis presented early results of the Phase III HAWK and HARRIER trials at Association for Research in Vision and Ophthalmology (ARVO), held April 29 to May 3 in Hawaii. Findings reported at the Academy of Ophthalmology meeting last year demonstrated that 57% of brolucizumab 6-mg patients in HAWK and 52% in HARRIER stayed on a 12-week dosing interval following the loading phase through week 48.1 The ARVO 2018 report showed that brolucizumab 6-mg patients had an 87% (HAWK) and 83% (HARRIER) probability of remaining on this quarterly treatment interval through week 48.2
“The ability to quickly identify patients who can maintain a 12-week interval has the potential to simplify treatment plans for nAMD patients,” says Glenn J. Jaffe, MD, of Duke University, and an author of the presentation. “These robust data may offer physicians confidence that when 12-week dosing with brolucizumab is initially successful, there is high probability that the patient will maintain this interval through the first year of treatment.”
Analysts have predicted Novartis would get FDA approval of brolucizumab for neovascular AMD next year and sales would peak at $2 billion if it also receives FDA approval for treatment of diabetic macular edema. The US patent on Lucentis expires in 2020. Lucentis had $3.38 billion in global sales in 2017. Novartis holds rights to Lucentis outside of North America.
Building a Better Lucentis
Meanwhile, Roche/Genentech has been collaborating with Ascendis Pharma on longer-acting ranibizumab. It would utilize Ascendis’ TransCon technology to extend out the dosing of Lucentis from monthly to up to six months. Successful development of the platform would further shift the landscape for Lucentis biosimilars.
Regeneron has not had an easy time of stretching out the dosing regimen of Eylea. Last year the Phase II RUBY and ONXY trials demonstrated that using the angiopoietin-2 antibody nesvacumab in combination with Eylea did not offer additional benefit over Eylea alone for treatment of diabetic macular edema. As a result, Regeneron decided not to go ahead with Phase III trials.
For questions about this article, please contact Richard Mark Kirkner at Rich@healthegy.com.
- Dugel P, et al. HAWK & HARRIER: 48-week results of 2 multi-centered, randomized, double-masked trials of brolucizumab versus aflibercept for neovascular AMD. Presented at: The American Academy of Ophthalmology 2017 Annual Meeting on November 10, 2017, New Orleans.
- Dugel P, et al. A Comparison of the anatomical efficacy of brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD): an analysis over 16 weeks of matched treatment in the HAWK and HARRIER studies. Presented at: the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting, Honolulu, HI.