Retina Anti-VEGF Biosimilars: How to Prepare for the Coming Wave

Home , Biogen, Viatris

MAY 2021

Contents

Executive Summary 3

Opportunities and Risks on the Path to Commercialization 4

Anti-VEGF Retinopathy: The Biosimilar Pipeline 5

Portrait of a Biosimilar Shakeup 6

A High Bar for Novel Retinopathy Therapeutics 9

Rheumatoid Arthritis Biosimilars: Lessons and Caveats 10

What Prescribers and Payers Think 11

Retinal Biosimilar Outlook and Scenarios 12

Tiered Introductions in Two Key Markets 12

Conclusion 14

2 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Executive Summary

Drugs that treat diseases of the retina, such as wet age-related macular degeneration (wet AMD), make up a well-defined category with two prominent brands— Eylea® (aflibercept) and Lucentis® (ranibizumab)— plus off-label use of the cancer treatment Avastin® (bevacizumab). All three molecules inhibit proteins called vascular endothelial growth A coming wave of factors (VEGF), which cause excessive blood-vessel growth. biosimilars in Europe, the Physicians, patients and payers have relatively clear expectations for U.S. and other markets— these products. But a coming wave of biosimilars in Europe, the U.S. as well as a version of and other markets—as well as a version of bevacizumab developed bevacizumab developed and marketed specifically for ophthalmic use—could radically transform the treatment ecosystem. and marketed specifically for ophthalmic use—could Eylea is the current sector leader. Sold by Regeneron and Bayer, radically transform the it will soon face biosimilar competition in major markets. So will Lucentis and Avastin, which are currently second and third in sales, treatment ecosystem. respectively. Together, the three anti-VEGF products have served patients well—but at significant cost to health systems. Biosimilars and ocular bevacizumab* will put downward pressure on pricing, without doubt. Yet the speed of physician uptake in all major markets is a persistent puzzle.

It is incumbent on biosimilar companies and brand innovators— as well as physicians and payers—to understand and prepare for the market transition ahead. This white paper will sketch a variety of scenarios based on anticipated launches of leading anti-VEGF biosimilars and ocular bevacizumab, as well as the arrival of novel retina therapeutics over the next three to five years. Examining historical data on biosimilar introductions in other therapeutic areas, we’ll derive lessons valuable to biosimilar companies and brand owners alike.

* Avastin (bevacizumab) is an innovative antibody developed for oncology indications and used off label for retinal disease. Bevacizumab molecules are included in this report because they have unique “biosimilar-like” clinical development qualities and because of the anticipated disruptive nature of bevacizumab labeled for ocular use. See page 7 for details.

3 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Opportunities and Risks on the Path to Commercialization

The arrival of retinal biosimilars presents a host of intertwined opportunities and risks for both market leaders and new entrants. Global demand for the products is enormous and growing as aging populations in key markets increase. AMD, the leading cause of vision loss in individuals 60 and older, is believed to affect nearly 200 million people globally today, and the number could grow to 288 million by 2040.1

As for hitting safety/efficacy targets and clearing regulatory review, the prospects for biosimilars are excellent in most instances. Analyzing data from 108 biosimilar programs in the Biomedtracker database, Swedish biosimilars company Xbrane found the average program entering Phase I trials had a 78 percent chance of winning market authorization.2 This compares to a 10 percent chance for the average novel therapeutic. Stripping out biosimilar programs that fail due to manufacturing issues or simply marketing decisions, the actual odds for success may be greater than 90 percent.

But market authorization is the starting gate, not the finish line. What matters more are decisions taken in the critical weeks or months between approval and launch, and the 12-18 months after a product reaches the market. These decisions must be informed by careful analysis of less tangible determinants, such as prescriber psychology and behavior and the evidentiary preferences of payers.

Balancing risks and opportunities within defined market scenarios is essential for branded and biosimilar anti-VEGF contenders alike.

In both the U.S. and Europe, players must understand how a medicine’s price, availability, reimbursement status, safety and efficacy affect the order in which prescribers recommend a treatment, as well as the relative weight they assign to each factor. Uncertainties include:

• How comfortable physicians will feel in prescribing biosimilar ranibizumab or aflibercept, or labeled bevacizumab, assuming safety and efficacy are similar to the originator products

• The amount of discounting providers will expect in order to make the switch We make sure important questions • Whether other incentives will be necessary bearing on commercial success if brand originators decide to match the discount get asked, iterated and answered. • To what degree prior authorizations, step therapies and other restrictions come into play

When Syneos Health® works with clients in clinical development, our field of view is never confined to milestones, regulatory approval or the moment of launch. Our cross-disciplinary commercial specialists work closely with clinical teams to ensure the most plausible market-altering scenarios are held in view through each stage of development. We make sure important questions bearing on commercial success get asked, iterated and answered.

4 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Retina Anti-VEGF Therapy: The Biosimilar Pipeline

Molecule Developers Target Market Development Status

Eylea Regeneron, Bayer,* Bayer (ex-U.S.)† Global Originator, approved and marketed

MYL1701P Viatris, Momenta Pharmaceuticals, Inc,* Phase III for DME recruitment complete (global) (now Johnson & Johnson)†

SB15 Samsung Bioepis, Biogen (ex-China),† Global Phase III for wet AMD recruiting (global) AffaMed Therapeutics (China)†

ABP938 Amgen Global Phase III for wet AMD recruiting (global)

FYB203 Bioeq GmbH, Formycon AG* Global Phase III for wet AMD recruiting (global)

SCO411 SamChunDang Pharmaceutical Co., Ltd. Global Phase III for wet AMD recruiting (global)

QL-1207 Qilu Pharmaceutical Co., Ltd. China Phase III for wet AMD recruiting (China)

N/a CinnaGen Co. Iran Phase III for wet AMD recruiting (Iran)

SOK583Al Hexal AG (Sandoz) Global Phase III for wet AMD recruiting (global)

ALT-L9 Altos Biologics (Alteogen Inc.), Global Phase I for wet AMD complete (Korea) Kissei Pharmaceutical Co., Ltd. (Japan)*

LY09004 Luye Pharma Co., Ltd. China Phase I for wet AMD complete (China)

GBS-012 Gene Techno Science, Kishi Kasei Co., Ltd.* Japan Preclinical

SCB-420 Clover Biopharmaceuticals Not disclosed Preclinical

Lupin’s ranibizumab Lupin Not disclosed Preclinical

Lucentis Genentech, Roche (U.S.),† Novartis (ex-U.S.)† Global Originator, approved and marketed

Razumab® Intas Pharmaceuticals India Biosimilar, approved and marketed

RanizuRel™ Reliance Life Sciences India Biosimilar, approved and marketed

SB11 Samsung Bioepis, Biogen (ex-China),† AffaMed Global European MAA for wet AMD accepted for review Therapeutics (China)†

FYB201 Bioeq GmbH, Formycon AG,* Coherus Global Phase III for wet AMD complete (global) BioSciences (U.S.)†

SJP-01333 / GBS-007 Senju Pharmaceutical, Gene Techno Science,* AsiaPacific Phase III for wet AMD complete (Japan) Ocumension Therapeutics (China, Taiwan)†

Xlucane® Xbrane Biopharma AB, STADA Arzneimittel AG,* Global Phase III for wet AMD recruitment complete Bausch + Lomb† (global)

Vicentis Zist Daru Danesh Iran Phase III for wet AMD recruitment complete (Iran)

Lupin’s ranibizumab Lupin India / Global Phase III complete (India), Phase III ongoing (global)

QL-1205 Qilu Pharmaceutical Co., Ltd. Global Phase III recruiting (global)

GNR-067 Generium Pharmaceutical Russia Phase III for wet AMD planned (Russia)

IDB0062 (biobetter) Ildong Pharmaceutical Not disclosed Preclinical

Avastin® Genentech Global Originator, used off label

Lumiere® Laboratorio Elea Argentina Biosimilar, approved and marketed

Lytenava™ (ONS-5010) Outlook Therapeutics, Syntone Technologies Global Phase III for wet AMD recruitment complete Group Co. Ltd. (China)* (global)

601 Sunshine Guojian Pharmaceutical China Phase I for wet AMD recruiting (China), (Shanghai) Co., Ltd. Phase II for CRVO planned (China)

TAB014 TOT Biopharm Co., Lee’s Pharmaceutical* Global Phase I for wet AMD complete (China)

JY028 Beijing Eastern Biotech China Phase I for wet AMD recruiting (China)

TK001 Jiangsu T-Mab Biopharma Co., Ltd China Phase I for wet AMD recruiting (China)

SCT510A SinoCellTech China Phase I/II for wet AMD planned (China)

*Development partner. †Commercial partner. DME = diabetic macular edema; MAA = marketing authorization application

5 Phase I Phase II Phase III Approved and marketed Preclinical European MAA RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Portrait of a Biosimilar Shake-up

For years, patients and prescribers in global markets have benefited from effective anti-VEGF treatments for diseases such as wet AMD, DME and diabetic retinopathy. The first blockbuster, Lucentis, was developed by Genentech—later absorbed into Roche—and sold by Novartis outside the U.S. Net sales came to about USD $3.8 billion in 2020. A little later, Regeneron and Bayer co-developed Eylea and have dominated major markets since launch. Eylea, which generated roughly USD $8 billion globally in 2020, gained the top spot because of similar efficacy to Lucentis, with less frequent dosing and less burden to the patient. With billions of dollars Regeneron has commercial rights in the U.S., and Bayer has ex-U.S. rights. at stake, biosimilar development is Third in this group is off-label Avastin. Originally developed as a cancer drug, it shows real-world results in ophthalmology comparable to Lucentis and Eylea advancing quickly. but at a fraction of the price—less than $100 for Avastin, compared with close to $2,000 for either Eylea or Lucentis.

The main patent for Lucentis expired in the U.S. in June 2020 and will expire in Europe in early 2022. Eylea’s patent expiration will follow in 2023 in the U.S. and 2025 in Europe. In emerging markets, some patent expirations may come even sooner.

With billions of dollars at stake, biosimilar development is advancing quickly. For Lucentis, three powerful, intercontinental manufacturing alliances will likely lead the charge: STADA/Xbrane, Formycon/Bioeq/Coherus, and Samsung Bioepis/ Biogen. Of these, Samsung Bioepis filed for biologic license application (BLA) approval for U.S. in November 2020, and for MAA approval for Europe in October 2020. Given typical review timelines, we can expect approval of the first biosimilar in the second half of 2021. Bioeq plans to file for BLA/MAA approval in mid-2021, and Xbrane could follow later in 2021. There are also several ranibizumab biosimilar developers in Asia and some (e.g., Qilu Pharmaceuticals) might also target the U.S. and EU markets.

Given the dominant market position of Eylea, the landscape of aflibercept biosimilar developers is even more crowded. Based on the data published in clinicaltrials.gov, Viatris might be ready to launch its biosimilar the day of patent expiration in 2023. Depending on how Samsung Bioepis, Bioeq and Amgen programs progress, all three could also be near the starting line in time. Competition will intensify with programs from Celltrion, Sandoz, Alteogen and others moving through the pipeline.

We expect additional biosimilars for Eylea and Lucentis to arrive in global markets between 2022 and 2025, along with more limited regional efforts confined to specific countries. Programs are on the fast track in China, India, Japan and Korea.

6 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Bevacizumab Wildcard Ongoing programs for bevacizumab (the active molecule in Avastin) for ophthalmology indications are also attracting attention. Several companies that have developed bevacizumab biosimilars in oncology may extend the use to wet AMD and/or DME, while others are developing their own products for retina indications specifically. Outlook Therapeutics is well advanced and plans BLA submission by December 2021 for Lytenava. That could lead to approval by late 2022 or early 2023 as the first bevacizumab developed exclusively for eye disease. Market entry in the EU could be even faster: in June 2020, an undisclosed company filled an MAA for bevacizumab use in wet AMD.

It should be noted that ocular bevacizumab products are not technically biosimilars, as there is no originator approval for retinal diseases. Any new bevacizumab in this category will be considered a novel therapeutic. But it will benefit from a vast literature and off-label use experience and could be highly disruptive, given potentially lower pricing and near-equal real-world outcomes.

How quickly will the new biosimilars and ophthalmic bevacizumab gain acceptance? Analyzing the treatment market for wet AMD, Datamonitor Healthcare predicts biosimilar aflibercept and ranibizumab will start showing their strength in the U.S., Japan and five major European markets in 2024.3

Combined sales of all biosimilar versions of both treatments should exceed $500 million for wet AMD that year and will likely continue to grow through at least 2029, Datamonitor anticipates.

7 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Predictions Are Tricky for Several Reasons

• In addition to matching reference products on safety and efficacy, biosimilar contenders must deliver substantial price reductions to win over payers and prescribers

• Further pressure may come from biosimilar versions of bevacizumab labeled for retinal indications, not cancer

• Brand owners Roche/Novartis and Regeneron/Bayer will not stand still as the biosimilar wave begins to break. Historically, faced with biosimilar competition, established brands have offered discounts of their own. In recent years, both camps have looked to extend product lines with add-on data and configuration updates, such as moving to prefilled syringes

• Development of novel therapeutics is ongoing—particularly aimed at lessening the burden of monthly or bi-monthly injections. One pipeline product garnering attention is Roche’s faricimab, the first-ever bispecific antibody that blocks both the VEGF and angiopoietin (Ang-2). Investigational treatments from Kodiak and Graybug similarly target new pathways. Further upstream in the development pipeline are gene therapies from Adverum and REGENXBIO, offering hope of one-time treatments for wet AMD

• Impacts from enhanced drug delivery may be significant. One example: Roche’s Port Delivery System, a refillable implant that cleared Phase III trials last summer, and which will enable patients to go six months between injections. The advent of novel drugs (so-called pipeline assets) may further slow biosimilar uptake

But with regard to these examples, there are important caveats. Novel assets are intrinsically unpredictable, as compared with biosimilars that emulate products whose safety and efficacy are established. A case in point: Novartis’s original wet-AMD drug Beovu®, approved in 2019, came under immediate safety scrutiny, causing the manufacturer to make additional research investments post-approval (see sidebar). Several newer therapies in the clinic may offer advantages in durability—but in each case, there are “unknown unknowns.”

Novel assets are intrinsically unpredictable, as compared with biosimilars that emulate products whose safety and efficacy are established.

8 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

A HIGH BAR FOR NOVEL RETINA THERAPEUTICS

On a 2- to 5-year year time horizon, the arrival of novel therapeutics could shake up the anti-VEGF space, compounding or perhaps complicating the desired pricing impact of biosimilars. No fewer than 15 new molecules are currently in or entering Phase III testing in Europe and the U.S. (including bevacizumab). But newcomers can’t count on easy sailing. Consider the recent history of two novel medicines that looked promising: abicipar pegol, from Allergan (now Abbvie), and Beovu (brolucizumab) from Novartis. Last May, a pair of Phase II studies indicated abicipar pegol was noninferior to Lucentis (ranibizumab) in achieving stable vision for people with wet AMD. And it required just 6 to 8 injections, versus 13 for ranibizumab. However, compared with the reference medicine, more patients experienced adverse events on abicipar pegol—particularly a high rate of intraocular inflammation. In June, the FDA handed Allergan a Complete Response Letter (CRL). The company is running additional trials to support a future resubmission of a more refined molecule. Novartis launched Beovu two months after Allergan’s CRL, but a subset of patients experienced vision loss and other issues, with several safety reports among early sales. Beovu now seems positioned as a second-line therapy for low responders to the older brands.

9 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Rheumatoid Arthritis Biosimilars: Lessons and Caveats

In sketching scenarios for ophthalmology biosimilars in Europe, it’s instructive to see how such kindred biologics have fared in other therapeutic areas. Humira (adalimumab) is a good use case. Four approved adalimumab biosimilars—from Amgen, Sandoz, Viatris and Samsung Bioepis/ Biogen—were launched almost simultaneously in Europe when Humira lost its patent in mid-October 2018. A fifth product, from Fresenius Kabi, followed a few months later. In the first 12 months of sales, these medicines together gained 47 percent market share.

What accounts for the success? Partly, it’s the impact of so many competitors in quick succession and concomitant, steep discounting. While biosimilars typically arrive in Europe at prices 25 percent to 30 percent below the brand product, Viatris, Amgen, Biogen and the others came in with a 40-percent discount. Adalimumab biosimilars also benefited from trails blazed by others. Large numbers of European physicians and patients were willing to switch from Humira because medical practices had largely positive experiences with biosimilar infliximab (Remicade®) and etanercept (Enbrel®)— all of them treating rheumatoid arthritis and other inflammatory diseases. Biosimilar adoption in the U.S. has proceeded at a slower pace overall, but deep discounting could change the picture.

In short, each biosimilar success in one therapeutic field prepares the ground for planting in others. We thus anticipate anti-VEGF biosimilar treatments in ophthalmology will benefit from positive physician/patient experiences in the inflammatory field.

The adalimumab biosimilar story contains additional, important lessons on how societies can maximize gains from the uptake of these products. Publishing in the journal Drugs,4 a team of pharmacologists and researchers in South Korea, the UK, Germany and other countries concluded that:

• Payers should revisit pharmacoeconomic assessments to make sure they accurately reflect the impact of biosimilar market entry, recognizing the enormous opportunity to improve patient care

• Physicians need a better understanding of biosimilars to increase their confidence in prescribing them, following guidelines to maximize cost savings

• Beware of “nocebo” effects. Improved physician communication strategies can help ensure patients do not conclude that biosimilars are less effective and, therefore, discontinue use

• Biosimilar developers may need to focus on additional innovation in order to compete in a market that may be crowded with look-alike products.

In short, each biosimilar success in one therapeutic field prepares the ground for planting in others.

10 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

WHAT PRESCRIBERS AND PAYERS THINK

In all major pharmaceutical markets, including those with single-payer systems, physician perceptions will affect the scope and speed of biosimilar uptake for retinal diseases. While biosimilars in this category are unfamiliar to many providers, recent data collected in the U.S. show we are likely to see rapid forward momentum.

In one small U.S. survey of community-based retina specialists (N=37), more than half of respondents said they were aware of retina biosimilars, and 70 percent said they’d like to receive educational information on safety, efficacy and performance.5 Eighty-three percent thought such products belong in the treatment armamentarium, but many expressed reservations as well. Asked about their primary concerns in prescribing such drugs, about one-third mentioned payer coverage.

In benchmarking U.S. payer acceptance of anti-VEGF biosimilars, we can also extrapolate from acceptance of off-label bevacizumab biosimilars in oncology. In February, publisher AIS Health discussed the matter with payer organizations including Prime Therapeutics, which provides pharmacy expertise to not-for-profit Blue Cross Blue Shield plans representing 30 million members. While biosimilars of bevacizumab have only been on the market since 2019, they already represent 46 percent of Prime’s commercial book of business in oncological uses of the therapy—and they may represent as much as 37 percent across all health plans.6

Experts consulted by AIS Health say provider perception will be shaped, not just by evidence of safety and efficacy, but by reimbursement patterns. For example, under a buy-and-bill arrangement for physician-administered products, doctors and practices will be vigilant about price and reimbursement gaps between branded and biosimilar products, which directly affect their own profit margins.

11 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Retinal Biosimilar Outlook and Scenarios

What will global markets look like as a myriad of contenders launch anti-VEGF biosimilars in the next next 1 to 3 years? Biosimilar programs generally are approved within 12 months after filing a BLA or MAA in the U.S. or Europe, respectively. But after that, market entry scenarios in these two key regions look quite different.

In the U.S. market, the impact of the first Lucentis biosimilar will depend on the initial discount offered by manufacturers. Following a pattern with other biosimilar introductions, we may see small-to-moderate discounts of 10 percent to 15 percent. At that level, a Lucentis biosimilar will likely gain market share slowly as it eats into sales of the originator brand.

The introduction of second and third Lucentis biosimilars will likely drive steeper discounts and bring further erosion of originator brand revenues. As prices fall, the Lucentis biosimilars will also pose a threat to sales of Eylea, as payers and physicians consider cost/benefits of the product’s preferred use. The launch of several Eylea biosimilars in 2023 could lead to another dip in sales prices in the anti-VEGF ophthalmology space overall.

It will be interesting to see how bevacizumab labeled for retinal indications will fit into this game. The dynamics for such products will be different. While biosimilars of Lucentis and Eylea will offer cheaper alternatives to the originator brands, labeled bevacizumab might be sold at a premium over off-label Avastin as currently prescribed, and price expectations by payers and physicians might also be different, vis-à-vis Lucentis/Eylea biosimilars.

Tiered introductions in Two Key Markets

U.S. market entry

Product launch Date

1st Lucentis biosimilar Late 2021

2nd and 3rd Lucentis biosimilar Mid/late 2022

Labeled bevacizumab Late 2022

1st Eylea biosimilar 2023

EU market entry

Product launch Date

Bevacizumab labeled for retinopathy Late 2021

1st Lucentis biosimilar Early 2022

2nd and 3rd Lucentis biosimilars Mid/late 2022

Eylea 2025

12 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

As for the EU, off-label use of Avastin is less common than in the U.S., in part because use is restricted in several countries. Availability of an approved bevacizumab could change prescription practices. It remains to be seen if bevacizumab labeled for ophthalmology will replace off-label use of Avastin and to what extent it will cannibalize sales of Lucentis and Eylea.

Recent biosimilar launches in other indications in Europe have come with significant discounts of around 40 percent. Given that three competitors could arrive in rapid succession, we would expect a similar situation for the first ranibizumab biosimilars. As in the U.S., a hefty drop in sales price for Lucentis biosimilars in Europe will not only put pressure on the originator brand but will most likely affect Eylea pricing as well. Much will depend on pricing responses from Novartis and Bayer, the European brand- holders of Lucentis and Eylea, respectively.

This means that when Eylea biosimilars arrive in the EU in 2025, the The exact dynamics manufacturers may have to contend with significantly lower pricing on Eylea. What’s more, the reduction in sales prices for Lucentis and Eylea and the detailed market could also have a knock-on effect on novel treatments such as Beovu or share disruption is hard others. Currently, their average selling prices are comparable to Lucentis to predict and will depend and Eylea, but that may not be sustainable. on the number and

The exact dynamics and the detailed market share disruption is hard sequence of biosimilar to predict and will depend on the number and sequence of biosimilar launches, initial biosimilar launches, initial biosimilar discounts and originator responses, the discounts and originator impact of one or more ocular bevacizumabs and price erosion over responses, the impact time. What seems certain is that the spread of anti-VEGF ophthalmic of one or more ocular biosimilars will lead to broader patient access to highly effective drugs and offer savings to the healthcare systems. bevacizumabs, and price erosion over time. What seems certain is that the spread of anti- VEGF ophthalmic biosimilars will lead to broader patient access to highly effective drugs and offer savings to the healthcare systems.

13 RETINA ANTI-VEGF BIOSIMILARS: HOW TO PREPARE FOR THE COMING WAVE

Conclusion

Whether you are biosimilar developer or a treatment innovator in the competitive retina space, the instinct that guides a successful strategy is the same. It is the willingness to balance competing perspectives while standing, in turn, in the shoes of the patient, the care provider and the payer. From this vantage point, persuasive evidence never reduces simply to safety and efficacy, cost savings, simplicity of use or vendor reputation.

For example, payers considering biosimilars are looking at more than clinical dossiers. They may have a close eye on commentary by advocacy groups, or on emerging viewpoints of ophthalmology associations and their specialty subgroups, as reflected in guidelines and amplified through social media.

These are some of the reasons Syneos Health emphasizes the synergies of clinical and commercial endeavor when working with clients in each of these different domains. The once-stable market for anti-VEGF retinopathy treatments is poised for transformation, bringing enormous hope to patients and their physicians. Companies with insight-driven strategies and clinical-commercial alignment will be the primary actors on this new stage.

1. Wong W L, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Global Health. 2014;2(2)e106-116. doi: 10.1016/S2214- 109X(13)70145-1. Accessed February 19, 2021. https://pubmed.ncbi.nlm.nih.gov/25104651/

2. Why Xbrane has chosen to focus on biosimilars. Xbrane.com. Accessed February 19, 2020. https://xbrane.com/en/ biosimilars/

3. Fontanilla D. 2020. Forecast: Wet age-related macular degeneration (Wet AMD). Datamonitor Healthcare. Informa Pharma Intelligence. Accessed February 19, 2020. https://pharmastore.informa.com/product/disease-analysis-wet-age-related- macular-degeneration/

4. Kim H, Reike A, Avedano L, et al. The future of biosimilars: maximizing benefits across immune-mediated inflammatory diseases. Drugs. 2020;80(2):99-113. Accessed February 20, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007415/

5. Oskouei S. Opinion: Is the ophthalmology market ready to embrace biosimilars? AJMC: The Center for Biosimilars. 2021. Accessed February 20, 2021. Accessed February 20, 2021. https://www.centerforbiosimilars.com/view/is-the- ophthalmology-market-ready-to-embrace-biosimilars-

6. 2021 Outlook: With 20 biosimilars available, U.S. Market is Heating Up. February 1, 2021. AIS Health. Radar on Specialty Pharmacy.

14 CONTRIBUTORS

Manfred Weiler, PhD Senior Vice President, Medical & Scientific Strategy, Syneos Health

Nicholas Spittal, MBA Senior Vice President Clinical Development, Syneos Health

Laszlo Bekesi, MD Vice President Clinical Development, Syneos Health

About the Syneos Health Insights Hub The Syneos Health Insights Hub generates future-focused, actionable insights to help biopharmaceutical companies better execute and succeed in a constantly evolving environment. Driven by dynamic research, our perspectives are informed by our insights-driven product development model and focused on real answers to customer challenges to help guide decision making and investment.

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