US Biosimilars Enjoy A Year Of Firsts In 2021
Two Interchangeable Biosimilars And First Ophthalmic Biosimilar Approved
Executive Summary
While US biosimilar approvals have been thin on the ground in 2021 – with products delayed due to the FDA’s inability to conduct certain facility inspections during the COVID-19 pandemic – the market has nevertheless seen several firsts this year, including two interchangeability designations and the first ophthalmic biosimilar approval.
With biosimilars gaining traction in the US in recent years thanks to multi-source competition on certain key products as well as healthy uptake in treatment areas such as oncology, 2021 saw the US biosimilars market take further steps forward with a number of firsts.
These included the first US FDA designations of biosimilar interchangeability, the launch of the first interchangeable biosimilar, and the first biosimilar to be approved by the FDA for ophthalmic indications.
However, at the same time several biosimilar developers saw their efforts to reach the market frustrated by delays to FDA approvals caused by the agency’s inability to conduct certain necessary facility inspections due to pandemic-related travel constraints.
Semglee Insulin Glargine Is First Interchangeable Biosimilar
The first US biosimilar approval of the year came in July, with the FDA’s formal designation of Viatris Inc.’s Semglee (insulin glargine-yfgn) biosimilar as interchangeable with Sanofi’s Lantus blockbuster. (Also see "Viatris Wins Landmark First US Interchangeability Designation For Semglee" - Generics Bulletin, 29 Jul, 2021.)
To meet this additional standard to biosimilarity, a product must not only be deemed biosimilar to its reference brand but must also demonstrate that it will “produce the same clinical result as the reference product in any given patient.”
Moreover, “for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product” must not be “greater than the risk of using the reference product without such alternation or switch.”
While industry views are still to some extent mixed on the desirability and necessity of interchangeability as a separate standard to biosimilarity in the US, the designation brings valuable prizes for successful applicants in the form of pharmacy-level substitution as well as a year of interchangeable biosimilar exclusivity for the first interchangeable biosimilar version of each product, dating from commercial launch of the interchangeable biosimilar.
In Viatris’ case, the launch of the interchangeable insulin glargine biosimilar – which followed some months after approval, in November2021 – offers the opportunity to build on the relatively low market share captured so far by the non-interchangeable version of Semglee, which is due to be rapidly phased out.
The company has also taken the step of launching the interchangeable biosimilar in both branded and unbranded versions, with the unbranded version offered at a wholesale acquisition cost of $147.98 for a pack of five 3ml pens and $98.65 per 10ml vial, representing a 65% discount to the list price of Lantus.
Meanwhile, the branded version of interchangeable Semglee comes in at a price that is a lot closer to the reference brand, with a WAC of $404.04 per pack of five 3ml pens and $269.38 per 10ml vial.
Humira Gets First Interchangeable Biosimilar Approval
Semglee was not the only biosimilar to be formally designated as interchangeable by the FDA in 2021. Several months later, in mid-October, the agency announced that Boehringer Ingelheim was to be the second recipient of an interchangeability designation, for its Cyltezo (adalimumab-adbm) rival to Humira.
The biosimilar – which was initially approved by the FDA in August 2017 – is scheduled to be among a chasing pack of Humira biosimilars that are expected to hit the US market in 2023, after Amgen launches its Amjevita (adalimumab-atto) version at the beginning of the year, under a series of settlement deals between biosimilar sponsors and originator AbbVie.
Boehringer Ingelheim has an expected launch date of 1 July 2023, putting it just after Samsung Bioepis on 30 June.
It remains to be seen how interchangeability will affect the biosimilars market more broadly and the biosimilar Humira market specifically. However, with so many adalimumab competitors expected to launch in the US from 2023 – the FDA has so far approved six Humira biosimilars, with more waiting in the wings – interchangeability and Boehringer Ingelheim’s year of interchangeable exclusivity could prove to be a significant differentiator.
Samsung Bioepis Bags First Ophthalmic Biosimilar
Another first for US biosimilars came in September 2021, when Samsung Bioepis Co., Ltd. – the joint venture between Samsung Biologics and Biogen Pharma– announced that it had received the FDA’s first approval for a biosimilar with ophthalmic indications, its Byooviz (ranibizumab-nuna) rival to Lucentis. (Also see "FDA Approves First Ophthalmic Biosimilar With Samsung Bioepis’ Lucentis Rival" - Generics Bulletin, 20 Sep, 2021.)
While biosimilar versions of Avastin (bevacizumab) are already available in the US – and, like the reference brand, are used off-label to treat eye disease – this has led to criticism from some quarters given the relative lack of supporting data in ophthalmic indications.
It was expected that Lucentis would face biosimilar competition in the US by the end of 2021. But as it received its Byooviz approval, Samsung Bioepis overturned these expectations by revealing that it would not launch the biosimilar before June 2022, following an undisclosed settlement with originator Genentech. “Pursuant to a global license agreement entered into with Genentech,” the company indicated, “Samsung Bioepis and Biogen will have freedom to market [Byooviz] in the US as of June 2022.” (Also see "US Lucentis Competition Expectations Upended By Byooviz" - Generics Bulletin, 22 Sep, 2021.)
Inspection Limitations Lead To Delays
Despite so many firsts for US biosimilars in 2021, some developers may see it as a year of missed opportunities to approve a greater number of biosimilars. International inspection constraints related to the COVID-19 pandemic prevented the FDA from conducting certain necessary inspections, pushing back the approval of multiple biosimilar candidates.
The first signs of this were seen at the very end of 2020, when Viatris and Biocon revealed that their bevacizumab candidate had been indefinitely delayed as the agency was unable to conduct a facility inspection.
Then, in September 2021, Alvotech revealed that its AVT02 adalimumab candidate – potentially the first US biosimilar version of the 100mg/ml higher-concentration presentation of Humira – had been similarly delayed. Alvotech had also been seeking interchangeability for its adalimumab biosimilar.
Notably, the FDA’s inability to approve these two biosimilars contrasts with the approach of the European Medicines Agency, which has seen fit to endorse both of these products this year. Viatris and Biocon gained a nod for their bevacizumab biosimilar in February while Alvotech’s filing for a higher-strength Humira biosimilar with partner Stada was granted a positive opinion recommending a marketing authorization by the EMA’s Committee for Medicinal Products for Human Use in September.
More recently, Fresenius Kabi AG acknowledged that its proposed pegfilgrastim biosimilar had suffered from the same uncertainty over the US agency’s ability to conduct a necessary inspection, with the product pushed back to a likely FDA approval in 2022, from an originally expected date of 2020.
Responding to queries over these biosimilar delays, the FDA said it was “actively working on an approach for addressing outstanding inspections.”
“FDA is currently employing other tools to evaluate facilities, as appropriate,” the regulator indicated, “such as requesting records and other information under section 704(a)(4) of the FD&C Act or reviewing trusted foreign regulator inspection records under existing mutual recognition agreements. These tools have, in many cases, successfully allowed us to take actions on applications in lieu of an FDA inspection.”
“FDA continues to monitor the public health situation as well as public health advisory travel restrictions,” the agency concluded. “Once safe travel can resume, inspections will be scheduled based on a number of factors including the public health impact.”
However, as the year draws to a close, China’s Bio-Thera Solutions is looking to achieve yet another first in 2021, pursuing what could be a landmark first FDA approval for a biosimilar developed by a Chinese manufacturer, in the form of its BAT1706 bevacizumab candidate. A goal date of 27 November 2021 for the firm’s application was disclosed earlier in the year.