AAV-RPGR(University of Oxford)

N. Czarnecki/MediaNews Group/Boston Herald via Getty Images Three weeks after snagging approval in the UK, the U.S. FDA approved Samsung Bioepis and Biogen's biosimilar drug. Byooviz is the first Lucentis copycat biologic to hit the market. Novartis and Roche's Lucentis was the first VEGF inhibitor available for wet age-related macular degeneration (AMD) fifteen years ago. Quickly rising to blockbuster drug status, sales began to fall somewhat over the past few years as Regeneron’s Eylea took its place as the leading AMD drug for annual profit. With 11 million people in the US affected with AMD, the leading cause of irreversible vision impairment in the over 60 crowd, the market is a huge one. Samsung Bioepis SVP Kyung-Ah Kim said the approval of Byooviz “underscores our continued commitment to providing valuable treatment options for people who do not have access to life-enhancing biologic medicines around the world.” The arrival of biosimilars to the market certainly change the profit landscape for companies whose patents are expiring. Lucentis sales for Roche had already declined 16% from 2019, generating $1.61 billion in 2020. The drop was credited to delay in treatment due to the COVID-19 pandemic. Injections are required monthly for the drug. However, Regeneron reported a 7% growth in 2020 global sales compared to the prior year for Eylea. The Biogen and Samsung Bioepis biosimilar-targeted partnership isn’t stopping at Lucentis. In a 2019 deal, Biogen also licensed SB15, a version of Regeneron and Bayer's Lucentis’ hottest competitor, Eylea. While safety and efficacy profiles on the two are similar, Eylea has a leg up on the market thanks to a reduction in frequency. In contrast to Lucentis’ monthly injections, Eylea patients receive 6-8 injections a year. While not able to offer the rock-bottom prices of generic drugs due to the complexity of development, biosimilars certainly help bring treatment costs down significantly for patients. In 2013, Lucentis ran about $2,000 per injection. “Biosimilars could help broaden patient access to more affordable treatments and generate healthcare savings to offset rising costs of these complex diseases while ensuring sustainability of healthcare systems,” Ian Henshaw, SVP and Global head of Biosimilars at Biogen said. In addition to the Eylea copycat in the works, Biogen also has exclusive commercial rights to three other Samsung Bioepis TNF inhibitor biosimilars in China for rheumatoid arthritis: Benepali, Flixabi and Imraldi. The licensing deal with Samsung Bioepis builds on Biogen’s push into the ophthalmology space. Over two years ago, Biogen acquired Nightstar Therapeutics for over $800 million. The deal scored a pipeline addition of a treatment for a rare and degenerative, X-linked inherited retinal disorder that leads to blindness. But this year, the gene therapy ended up being a bust. In a Phase II/III trial, cotoretigene toliparvovec missed its goal of improving retinal sensitivity. With the FDA approval of Byooviz, Samsung Bioepis now has five biosimilars approved in the U.S.

John Tlumacki/The Boston Globe via Getty Images Less than two weeks after Ginkgo Bioworks announced a merger with special purpose acquisition company (SPAC) Soaring Eagle Acquisition Corp., it announced a collaboration partnership with Biogen. The two companies, they claim, “aim to redefine the industry standard for manufacturing recombinant adeno-associated virus (AAV)-based vectors.” This is a hot area in gene and cell therapies. Gingko Bioworks is known as “the organism company.” Its focus is on using microorganisms to engineer various products in a vast swath of markets. This includes fragrances, food and agriculture, antibiotics, vaccines, therapeutics and enzymes. In November 2020, Gingko was offered a $1.1 billion loan from the U.S. government for COVID-19 testing and manufacture of raw materials for possible therapies. After its merger with Soaring Eagle and the resultant initial public offering (IPO), it is expected to have a market value of $15 billion. Under the terms of the deal with Biogen, the company will have access to Ginkgo’s cell programming platform. Gingko will use its technology and resources to improve the AAV production titers of Biogen’s gene therapy manufacturing. Biogen is paying Ginkgo $5 million up front, with milestone payments up to another $115 million. “We believe that Ginkgo’s unique combination of cell programming expertise, proprietary tools and knowledge of biological systems make them an ideal collaboration partner to explore a large number of design ideas with the goal of optimizing constructs,” said Alphonse Galdes, Head of Pharmaceutical Operations and Technology at Biogen. “They share our goal of ensuring approved therapies are not delayed by manufacturing constraints and are available to patients worldwide.” Biogen has a big date just around the corner. The U.S. Food and Drug Administration (FDA) has a target action date of June 7 for Biogen’s aducanumab for Alzheimer’s disease. The drug has had a complex history, with a significant amount of controversy. The drug was initially dropped in March 2019 after data suggested it would not meet its primary endpoint. Further data analysis found the drug was promising at the highest dose in a subpopulation. After further investigation, they submitted the application to the agency. If approved, analysts have projected annual sales of about $4.8 billion by 2026. However, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee voted against the drug. The most optimistic analysts have the odds for approval at about 50/50. And earlier this month, Biogen reported that its gene therapy for X-linked retinitis pigmentosa (XLRP), cotoretigene toliparvovec, missed the primary endpoint of the Phase II/III XIRIUS trial. XLRP is a rare, inherited disease of the retina. The company otherwise observed positive trends in some of its secondary endpoints. The therapy is an AAV8 vector-based gene therapy administered by subretinal injection. It allows for delivery of a full-length functioning retinitis pigmentosa GTPase regulator (RPGR) protein in XLRP patients whose disease is the result of RPGR gene mutations. But the Gingko deal is only the latest in a stream of agreements that show Biogen is working seriously on developing its gene therapy capabilities. Only a week before the trial announcement, Biogen signed a strategic collaboration deal with Capsigen to engineer novel AAV capsids for gene therapy. Washington-based Capsigen uses a proprietary TRADE platform and technologies to find and develop novel AAV capsids for disease-specific transduction profiles. And in March, Biogen announced plans to build a new gene therapy manufacturing facility in North Carolina to support its manufacturing for itself and its partners. Earlier in the year, the company signed a licensing deal with Germany’s CEVEC Pharma for its ELEVECTA Technology to manufacturing AAV vectors for gene therapies. And in January, Biogen and Germany’s ViGeneron GmbH inked a gene therapy collaboration focused on AAV therapies for inherited eye diseases. Jason Kelly, chief executive officer of Ginkgo Bioworks, said, “We are excited to collaborate with Biogen as they aim to develop treatments that may potentially slow, halt or cure neurological and neurodegenerative diseases and seek to enhance the industry standard for AAV manufacturing. Synthetic biology is leveraging the power of living cells to develop the next generation of therapeutics, everything from CAR-T, to CRISPR and gene therapies, which we believe will have a material impact on the lives of many.”