Diabetic macular edema (DME) occurs in patients with diabetes as a consequence of diabetic retinopathy and is typically referred to as the leading cause of blindness in diabetic patients. With the growing diabetic population and population ageing, DRG estimates that the prevalence of DME will grow over the next ten years to nearly seven million in the seven major pharmaceutical markets.1 DME typically develops in the advanced stage of diabetic retinopathy (DR) and is characterized by leaking fluid from abnormal blood vessels in the eye which can lead to swelling of the macula and visual impairment. The location of edema/hard exudates determines the severity of DME, with the disease being most severe when the center of the macula is involved and may result in vision loss, if left untreated.
What are the current treatment dynamics in diabetic macular edema?
Intravitreal (IVT) pharmacotherapies are the standard-of-care for patients with center-involved DME, with vascular endothelial growth factor (VEGF) inhibitors being the typical first-line choice because of their proven efficacy and safety. Three VEGF inhibitors are used in DME—the approved agents Eylea (Regeneron/Bayer HealthCare/Santen) and Lucentis (Roche/Genentech/Novartis) and off-label, low-cost Avastin (Roche/Genentech). Interestingly, despite Eylea being the last entrant in the anti-VEGF segment, it has emerged as a patient-share leader in some G7 countries and generates billion dollar sales in the DME market in the G7.2 DRG’s primary market research with retinal specialists indicates that preference for Eylea is largely driven by positive findings from the DRCR.net Protocol T study in which Eylea demonstrated superior efficacy to Avastin and Lucentis 0.3 mg at one year among patients with worse visual acuity at baseline.2 In fact, U.S. ophthalmologists surveyed by DRG generally considering Eylea to be the best-performing DME therapy on various clinical factors, including efficacy attributes.3, 4
In addition to VEGF inhibitors, IVT corticosteroid implants—Allergan’s Ozurdex and Alimera Sciences’ Iluvien—are approved for the treatment of DME. However, these agents are largely reserved as later-line options among patients with suboptimal response to VEGF inhibitors because of the risk of steroid-induced side effects with these therapies and prescribing/reimbursement restrictions in some markets.
How will key events impact the diabetic macular edema market?
- Continued use of low cost off-label Avastin, particularly in the United States: In some markets like the United States, the cost and reimbursement status of DME drugs are among the most important factors influencing physicians’ prescribing decisions. As such, retinal specialists in the United States continue to treat many of their DME patients with off-label Avastin, despite the availability of multiple approved agents, because it is by far the least expensive therapy for DME. Similarly, in some European countries, budget and regional restrictions motivate retinal specialists to administer off-label Avastin to their DME patients.5 Moreover, the increasing emphasis on affordable medications could restrict access to costlier drugs, as noted in the recent ruling by CMS in the United States stating that Medicare Advantage plans can allow step therapy to be used for Part B drugs (such as Eylea and Lucentis) for some patients as of January 1, 2019.6, 7 Thus, physicians may be forced to try Avastin first in their DME patients, in turn limiting patient shares for Eylea and other branded therapies, particularly in newly diagnosed DME patients.
- Biosimilars for Lucentis and Eylea: Biosimilar versions of Lucentis (ranibizumab) and Eylea (aflibercept) are expected to enter the major markets starting in 2020 and 2022, respectively. DRG research indicates a high physician receptivity to these biosimilars, assuming they have sufficient clinical evidence establishing that their safety and efficacy is comparable to the corresponding brands.3, 5 Given that biosimilars are expected to be available at discounted prices versus the brands, we anticipate a moderate decline in patient shares and sales for Lucentis and Eylea with the entry of these biosimilars. However, we anticipate that biosimilar ranibizumab—expected to launch earlier than biosimilar aflibercept—will have minimal impact on Eylea because of Eylea’s established clinical benefits, thus insulating Eylea branded sales until the later launch of biosimilar aflibercept.2
- Potential launch of two new therapies in DME: Much of the ongoing development in DME focuses on two key unmet needs—products with improved efficacy and products with more-convenient delivery profiles than VEGF inhibitors. These areas continue to be of interest because a proportion of DME patients do not experience significant improvements in vision with VEGF inhibitors and there is a large treatment burden associated with these agents due to their frequent IVT administration. Therefore, the entry of two late-phase agents—Novartis’s brolucizumab, a VEGF inhibitor, and Roche’s faricimab, a novel VEGF/Ang-2 inhibitor—will impact prescribing dynamics in DME, given they are designed to address these key unmet needs. Indeed, current evidence suggests that brolucizumab could have less-frequent dosing than Eylea9 and faricimab could have superior efficacy and/or less-frequent dosing than treatment mainstays.10, 11 However, the position of these drugs in the treatment algorithm and their performance in the DME market ultimately hinges on the outcomes from the ongoing Phase III studies in DME wherein the drugs are being compared with Eylea,6 the current efficacy benchmark.
What is the future commercial outlook in diabetic macular edema?
With these key market events expected over the next decade, treatment decisions for DME will become increasingly complex as the treatment armamentarium expands. The launch of biosimilars of ranibizumab and aflibercept and the continued reliance on off-label, low-cost Avastin will constrain sales in the DME market over the next decade. However, the launch of new products brolucizumab and faricimab will help drive market growth in the G7. Additionally, the expected entry of Allergan’s abicipar pegol and Allegro Ophthalmics’ Luminate (risuteganib) into Phase III development for DME in 2019 indicates toward the possibility of further market expansion. Nevertheless, given Eylea’s proven clinical profile in DME and physicians’ positive perceptions related to agent, we currently expect that it will continue to be a preferred agent in DME, capturing commendable patient share and sales.
Contact us today to learn how to access DRG’s diabetic retinopathy and diabetic macular edema research and reports:
- Decision Resources Group. Diabetic Macular Edema | Epidemiology | Mature Markets Data | January 2018
- Decision Resources Group. Diabetic Retinopathy/Diabetic Macular Edema | Disease Landscape & Forecast | G7 (update publishing in December 2018).
- Decision Resources Group. Diabetic Retinopathy/Diabetic Macular Edema | Access & Reimbursement | US | June 2018.
- Decision Resources Group. Diabetic Macular Edema | Unmet Need | US/EU | June 2018.
- Decision Resources Group. Diabetic Retinopathy/Diabetic Macular Edema | Access & Reimbursement | EU5 | August 2018.
- www.clinicaltrials.gov, accessed November 29, 2018.
- HHS, press release, August 7, 2018, accessed December 5, 2018. https://www.hhs.gov/about/news/2018/08/07/trump-administration-gives-medicare-new-tools-to-negotiate-lower-drug-prices-for-patients.html
- CMS, press release, August 7, 2018, accessed December 5, 2018.
- Novartis, press release, June 20, 2017.
- Roche, press release, 12 February, 2018.
- Roche, press release, 29 October, 2018.