Skylar Jeremias

Hi, I’m Skylar Jeremias for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

Here are the top 5 biosimilar articles for the week of January 23, 2023.

Number 5: IQVIA’s Global Use of Medicines Report for 2023 has revealed increased uptake of biosimilars around the world and predicted that biosimilars could generate 

, Kyung-Ah Kim, executive vice president of Samsung Bioepis, offered insight into how developers view the current biosimilars market, the relevance of interchangeability, and the usefulness of clinical efficacy testing.

Number 3: Patent litigators from Fish & Richardson, an intellectual property law firm, regaled audiences during a webinar covering all the big biosimilar regulatory and legal decisions throughout 2022, including 

Number 2: Sophia Z. Humphreys, PharmD, MHA, BCBBS, of Sutter Health in Sacramento, California, detailed the regulatory decisions from 2022, what's to come in 2023, and how the US biosimilars market is 

 for their respective license partnerships; Samsung Bioepis sped up interchangeability study for its adalimumab biosimilar; Dong-A ST shared positive phase 3 results for its ustekinumab biosimilar.

To read all of these articles and more, visit 

Videos

The Top 5 Biosimilar Articles for the Week of January 23

Saudi Arabia approved an adalimumab biosimilar, a denosumab biosimilar entered the market in the Republic of Korea, and Dr. Reddy’s Laboratories announced the completion of a phase 3 study for its rituximab biosimilar.

Alvotech and Bioventure said that the Saudi Food & Drug Authority approved AVT02, an adalimumab biosimilar referencing Humira, for manufacturing and distribution throughout Saudi Arabia, according to a report from 

The drug has received indications for rheumatoid arthritis as well as several other inflammatory diseases, such as psoriasis and inflammatory bowel disease. In Saudi Arabia, the biosimilar will be marketed under the name Simlandi.

AVT02 is the first biosimilar under Alvotech and Bioventure’s strategic partnership to receive regulatory approval in Saudi Arabia. As part of the agreement, Alvotech will be responsible for development and manufacturing and Bioventure will be in charge of marketing and distribution.

“We look forward to bringing this essential treatment to patients in Saudi Arabia as well as other key markets in the Middle East and North Africa," said Ashraf Radwan, Division CEO of GHH, Bioventure’s parent company.

AVT02 has also been approved by the European Medicines Agency and Health Canada. It is currently under review with the US FDA, with a manufacturing facility inspection scheduled for March 6, 2023 and a decision date of April 13, 2023.

Republic of Korea Welcomes a Denosumab Biosimilar

 said HK inno.N entered into an exclusive license agreement with mAbxience for a denosumab biosimilar referencing Prolia/Xgeva for the Republic of Korea market.

The biosimilar will be used to treat and prevent osteoporosis and cancer-related skeletal complications. Under the agreement, HK inno.N will hold the marketing rights for a 60 mg version of the biosimilar and a 120 mg version. mAbxience will be responsible for obtaining domestic approval and proceeding with sales.

“Due to excellent efficacy and convenience, the market for denosumab is steadily growing…. Through the introduction of biosimilars, we will provide new treatment options for osteoporosis patients and cancer patients suffering from skeletal complications,” said Kwak Dal-won, CEO of HK inno.N.

Dr. Reddy’s Announced Rituximab Progress

Dr. Reddy’s Laboratories, a Hyderabad, India-based company, shared that it had successfully completed the 

 needed to obtain approval for its rituximab biosimilar candidate (DRL_RI). The company said that it plans to submit to the FDA and the European Medicines Agency as well as regulatory authorities in other regions.

DRL_RI references Rituxan, a cluster of differentiation 20 directed cytolytic antibody used in the treatment of adult patients with rheumatoid arthritis, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, pemphigus vulgaris, granulomatosis with polyangiitis and microscopic polyangiitis.

The biosimilar is already approved in India and over 25 other emerging markets. The company conducted additional clinical development processes to meet the regulatory requirements of the United States, the European Union, and other highly regulated markets.

“This is a very important milestone in our biosimilars journey. The successful completion and positive outcome of these clinical studies highlights our capability for global clinical development of biosimilar products for highly regulated and global markets. These results underscore our commitment to developing high quality biosimilars and reinforce the potential of DRL_RI as a safe and effective treatment option to patients across the globe,” said Jayanth Sridhar, PhD, global head of biologics at Dr. Reddy’s.

Dr. Reddy’s is in the process of collaborating with its partner Fresenius Kabi for the commercialization of DRI_RI in the United States.

Articles

Biosimilars Check-in: Approval in Saudi Arabia, Launch in Republic of Korea, Dr. Reddy’s Completes Study

IQVIA’s Global Use of Medicines Report for 2023

, biosimilars were projected to generate $290 billion in savings around the world through 2027, which is lower than originally predicted, highlighting the need for policies that foster wider utilization of these products.

“COVID-19 continues to have an impact on pharmaceutical markets globally…. However, there are significant uncertainties in the years ahead with the transition of the global COVID-19 pandemic to a new phase where vaccines and therapeutics are available but are used inconsistently,” said Murry Aitken, senior vice president and executive director of the IQVIA Institute for Human Data Science and an author of the report, in a 

Overall, global medicine spending, meaning the amount spent purchasing medicines from a manufacturer before discounts and rebates, is expected to increase 3% to 6% per year through 2027, when it is projected to reach $1.9 trillion. Spending in Europe is expected to increase by $59 billion through 2027, with a focus on generics and biosimilars. The pandemic has had varying impact on countries throughout the Asia-Pacific region, but steady growth was projected after 2021. The main key drivers of spending growth include the contribution of new products, the effects of patent expiries, and the market introduction and increased uptake of biosimilars.

The report predicted that spending in North America will slow over the next 5 years as a result of the “relatively smaller contribution from new products” and the impact of several blockbuster reference products losing patent protections, including Humira (adalimumab) and Stelara (ustekinumab). The impact of market exclusivity losses is projected to increase to $140.8 billion over 5 years.

Dramatic volume uptake is possible with the approval of interchangeable adalimumab and 

 around the relationship of interchangeability, alternative originator formulations, and the commercial and negotiating strategies of stakeholders, which could dramatically increase or reduce the impact of these biosimilar events,” the authors wrote.

The report also pointed out portions of the Inflation Reduction Act that are expected to have an impact on medicine pricing and cost-sharing among beneficiaries in the United States, including a new drug inflation rebate policy, a redesign of Medicare Part D benefits, allowing Medicare to 

 drug prices with manufacturers, and a maximum 

 for insulins for patients enrolled in Medicare Part B or Part D plans.

Global spending in biotechnology is anticipated to exceed $660 billion by 2017, with a slowing growth rate of 7.5% to 10.5% attributed to savings from biosimilar utilization. Global savings from biosimilars will reach $383 billion between 2023 and 2027, reaching an annual savings of $100 billion in 2026 and 2027, when some of the reference products with the largest spending will have several years of well-developed biosimilar competition.

“Incremental usage of biologic therapies has been observed in periods after biosimilar entry, and this is expected to be particularly important in lower-income countries, but the largest savings will still be focused on developed markets, which already have very high levels of usage and spending on the originator versions of these medicines,” the authors noted.

By therapeutic area, immunology, oncology, and diabetes will see the most impact on spending as a result of biosimilar competition.

Global oncology spending is projected to reach $370 billion by 2017, with a slow growth rate of 13% to 16% as new medicines are offset by biosimilar competition. However, spending in this field is expected to increase by $184 billion by 2027, a 95% upsurge, partly because relatively few biosimilars are expected in oncology until later in the decade, when drugs like Ibrance (palbociclib) lose market exclusivity.

The spending in the immunology field will experience a slowed growth rate of 3% to 6% through 2027 due to biosimilars, which could see a 12% annual growth rate in this space. Although spending will likely grow by 24% by 2027, amounting to $34 billion, more than half of current immunology spending will face generic or biosimilar competition in the next 5 years.

IQVIA’s Global Use of Medicines Report for 2023 has revealed increased uptake of biosimilars around the world and predicted that biosimilars could generate nearly $300 billion in savings by 2027.

Global Use of Medicines Report Predicts Biosimilars Will Save $290 Billion by 2027 

A new report from HHS has revealed that if the Inflation Reduction Act (IRA) had been implemented in 2020, Medicare Part D and Part B beneficiaries could have saved a total of $734 million and $27 million, respectively, on insulin products.

When the IRA was passed in 2020, it included a provision to cap Medicare beneficiaries' out-of-pocket (OOP) costs for reference and biosimilar insulin products to $35. A measure to extend the cap to patients covered by private insurance companies 

 in August 2022. The Medicare insulin cap went into effect for Part D plans on January 1, 2023, and will go into effect for Part B plans beginning July 1, 2023.

On average, the researchers estimated that 1.5 million beneficiaries covered by Part B or Part D plans missed out on $500 in savings on insulin per member per year by the provision not being in effect in 2020. The report was conducted by the HHS Office of the Assistant Secretary for Planning and Evaluation.

“The Biden-Harris Administration is committed to lowering health care costs and increasing access to high-quality, affordable health care, and the Inflation Reduction Act is helping us do just that…. Thanks to this historic law, people who get their insulin through Medicare won’t have to pay more than $35 for a month’s supply. No one should have to skip or ration their insulin because they can’t afford it,” said Xavier Becerra, HHS secretary, in a statement.

The states with the most people with Medicare Part D or Part B that will benefit from the new provision are Texas (n = 114,000), California (n = 108,000), and Florida (n = 90,000). However, the states that will likely have the highest average annual OOP savings per beneficiary are North Dakota ($805), Iowa ($725), and South Dakota ($725).

“Americans are seeing a strong economy where they live…they are seeing prices down at their pharmacies…. I am more confident than ever that America’s best days are ahead,” commented President Joe Biden in a 

The report sent to Congress examined the role that insulin plays in diabetes treatment and reviewed evidence on how the cost of insulin affects treatment adherence and downstream health consequences. Also included were some policy efforts that could improve the affordability of insulin.

In 2019, about 37% of insulin prescriptions filled by people with Medicare required cost-sharing that exceeded $35 per fill, of which 24% of fills exceeded $70 per fill.

A global survey from 2019 found that 25.9% of US respondents reported having 

 in the previous year, nearly 20% higher than the percentage of respondents from other high-income countries. Additionally, a team at the Yale Diabetes Center found that 

 at the urban clinic at Yale reported some type of cost-related insulin underuse in the past 12 months, which included using less insulin than prescribed, not filling a prescription, and stopping insulin treatment completely.

 in March 2020 as part of the Part D Senior Savings Model, which former President Donald Trump signed an executive order to establish. The model was designed to save beneficiaries who take reference or biosimilar insulin products an average $446 in annual OOP costs for insulin, representing a 66% reduction in the average cost-sharing for insulin. The model was projected to generate $250 million in savings for the federal government over 5 years.

According to Becerra, the 1.5 million beneficiaries now impacted by the IRA’s cap do not include patients who already had their insulin costs capped at $35 through the Senior Savings Model. “Overall, we're looking at all Medicare beneficiaries who are taking insulin. And we're looking to see what they were actually paying out-of-pocket…. We're only counting the 1.5 million as folks who were paying more than $35 a month.”

A new report from HHS has revealed that if the Inflation Reduction Act (IRA) had been implemented in 2020, Medicare Part D beneficiaries could have saved a total of $734 million, averaging out to about $500 per member.

IRA Insulin Cap Could Have Saved Medicare Beneficiaries Millions in 2020

Alteogen and Alvotech announce updates for their respective license partnerships; Samsung Bioepis speeds up interchangeability study for its adalimumab biosimilar; Dong-A ST shares positive phase 3 results for its ustekinumab biosimilar.

New Licensing Agreements for Alteogen, Alvotech

Daejeon, Republic of Korea–based Alteogen entered into an 

 with Sandoz to develop and commercialize a subcutaneous version of a Sandoz biosimilar products using Alteogen’s Hybrozyme Technology. The agreement also includes an option to license the technology for 2 further products.

Alteogen will receive upfront payments and milestone payments as Sandoz meets specified development, regulatory, and sales milestones. Alteogen will also receive tiered royalty payments for sales of the commercialized product. The products included in the deal were not disclosed publicly.

 with Fuji Pharma, granting the latter the commercialization rights to an undisclosed biosimilar candidate in Japan. The companies have been in an exclusive partnership agreement since November 2018.

Samsung Bioepis Provides Updates on Adalimumab Biosimilar

Samsung Bioepis disclosed that it received domestic product licensing for its adalimumab biosimilar referencing Humira in the Republic of Korea, according to 

. The biosimilar was approved as a prefilled syringe (40 mg/0.4 mL) and an auto-injector pen (40 mg/0.4 mL) and will be marketed under the name Adalloce. The product is a high-concentration, citrate-free formulation.

Adalloce will be used to treat patients with rheumatoid arthritis, psoriatic arthritis, axial spinal arthritis, Crohn disease, psoriasis, ulcerative colitis, Becchett enteritis, purulent hives, and nephritis in adults, and Crohn disease, idiopathic arthritis, and plate dryness in pediatric patients.

 reported that Samsung Bioepis is speeding up the processes for obtaining an interchangeability designation for Adalloce in the United States, where it will be marketed as Hadlima when it enters the US market in July 2023.

The company originally planned to complete the study needed to obtain the designation by September 2023. However, it will now aim to finish the study in May 2023. When Hadlima launches, the biosimilar will not have an interchangeable label and it will be marketed by Samsung Bioepis’ US licensing partner Organon.

Dong-A ST Shares Phase 3 Ustekinumab Results

Dong-A ST, a company based in the Republic of Korea, announced that a phase 3 therapeutic equivalence study demonstrated that the company’s ustekinumab biosimilar (DMB-3115) has similar safety and efficacy profiles to the reference product (Stelara), according to a report from 

Ustekinumab products are used to treat inflammatory diseases, including Crohn disease, ulcerative colitis, plaque psoriasis, and psoriatic arthritis. Stelara is one of the highest-grossing biologic drugs in the world, accumulating $16.8 billion in global sales during the third quarter of 2022.

The phase 3 study conducted in 2021 in the United States and 9 other countries, such as Poland, Estonia, and Latvia. The study included 605 participants with moderate to severe chronic plaque psoriasis and evaluated the safety, efficacy, and immunogenicity of DMB-3115 over 52 weeks.

DMB-3115 has been jointly developed by Dong-A Socio Holding and Meiji Seika Pharma since 2013. Dong-A ST received the commercialization and development rights to the biosimilar in July 2020.

Eye on Pharma: New Partnerships; Samsung Adalimumab Updates; Phase 3 Ustekinumab Results

Celltrion Healthcare’s candidate bevacizumab biosimilar 

 demonstrated equivalent efficacy, safety, and immunogenicity to Avastin, the European Union (EU) reference product, in a 

 in patients with metastatic or recurrent non-squamous non–small cell lung cancer (nsNSCLC).

Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). It inhibits VEGF from binding to cell surface receptors to limit tumor vascularization and tumor growth. Bevacizumab is approved in the United States and EU for treating metastatic NSCLC, in combination with chemotherapy.

 are available on the US and EU markets, and CT-P16 has demonstrated 

 to the reference product. The current study is an ongoing randomized, double-blind, parallel-group, phase III trial conducted across 164 study sites in 21 countries. The authors have published data for the first part of the study, which includes data up to 1 year of follow-up for the last patient enrolled, and said that full data for the entire study period will be published after the study is completed.

Patients (n = 689) with stage 4 or recurrent nsNSCLC were randomized to receive the bevacizumab biosimilar candidate CT-P16 or EU reference product combined with paclitaxel and carboplatin chemotherapy for up to 6 cycles as induction therapy. Patients with controlled disease after induction therapy then continued maintenance therapy with the same drug. A total of 499 patients completed the induction period, and 466 (n = 239 in the CT-P16 group; n = 227 in the originator group) entered the maintenance therapy period.

Computed tomography scans to evaluate response to therapy were conducted multiple times throughout treatment. According to the authors, the baseline characteristics, medical history, and previous treatments between the two groups were “well balanced.”

Equivalent Objective Response Rate in CT-P16 and EU Reference Product Groups

The primary efficacy endpoint was the objective response rate (ORR), based on best overall response, according to RECIST criteria version 1.1 during the induction period. Secondary endpoints included response duration, time to progression (TTP), progression-free survival (PFS), and overall survival (OS).

The primary efficacy endpoint (ORR) was 42.40% (95% CI, 37.16-47.64) in the biosimilar group and 42.07% (95% CI, 36.88-47.27) in the reference product group. The 95% confidence intervals were within the predefined equivalence margins.

The authors said the approximately 42% ORR in both treatment groups was “comparable” to historical clinical trial data on reference bevacizumab with paclitaxel and carboplatin. They added that a similar proportion of patients in each group achieved a complete response (CR; 0.6% in the biosimilar group and 0.9% in the originator group) or partial response (PR; 41.8% and 41.2%, respectively).

Among secondary endpoints, response duration in patients achieving a CR or PR was similar between groups, 7.2 months for CT-P16 (95% CI, 6.3-8.2) and 6.3 months for the reference product (95% CI, 5.8-7.5). Median TTP, PFS, and OS were also similar between groups, according to the authors.

The authors noted final safety data will be available following completion of the study, which is still ongoing. Up to the data cut-off date (1 year of follow-up for the last patient enrolled), most patients experienced 1 or more treatment-emergent adverse events (TEAEs; 96.2% of patients in the biosimilar group; 93% in the reference product group). 51.6% of patients in the biosimilar group and 50.6% of patients in the reference product group experienced TEAEs considered to be related to the use of bevacizumab. Most TEAEs were grade 1 or 2 in severity, and the most common were alopecia (63.8% of patients in the biosimilar group; 63.4% in the reference product group) and anemia (31.6% and 27.0%, respectively).

Three deaths were considered related to the study drug in the biosimilar group, 1 each from pulmonary hemorrhage, sepsis, and subarachnoid hemorrhage. Seven deaths were considered related to the study drug in the EU reference product group, 2 from pulmonary hemorrhage and 1 each from cardiac arrest, cerebral infarction, lung abscess, septic shock, and sudden death.

The most common TEAE of special interest was hypertension, occurring in 12.8% of patients in the biosimilar group and 11.3% in the reference product group. Most were of grade 2-3 in severity.

Regarding immunogenicity, 22.6% and 24.1% of patients were positive for antidrug antibodies at any time during the study in the biosimilar and reference product groups. The authors said the proportion of patients positive for neutralizing antibodies was “low and similar between treatment groups” (2.3% in the CT-P16 group; 2.3% in the reference product group).

The authors concluded that CT-P16 demonstrated equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity to the reference product in patients with nsNSCLC after 1 year of follow-up. They added their results also suggest comparable survival outcomes, pharmacokinetics, safety, and immunogenicity. As the study is ongoing, they said, “full data for secondary endpoints due to be assessed during the whole study period, as well as longer-term safety data, will become available upon study completion.”

Verschraegen C, Andric Z, Moiseenko F, et al. Candidate bevacizumab biosimilar CT-P16 versus European Union reference bevacizumab in patients with metastatic or recurrent non-small cell lung cancer: a randomized controlled trial. 

. 2022;36(6):749-760. doi:10.1007/s40259-022-00552-8

Celltrion Healthcare’s candidate bevacizumab biosimilar CT-P16 demonstrated equivalent efficacy, safety, and immunogenicity to Avastin (reference bevacizumab), in a phase 3 clinical trial in patients with non–small cell lung cancer (NSCLC).

Phase 3 Study Finds Bioequivalence Between Celltrion Bevacizumab Biosimilar, Avastin for NSCLC

Here are the top 5 biosimilar articles for the week of January 16, 2023.

 STADA Arzneimittel and Xbrane Biopharma’s Ximluci, a ranibizumab biosimilar referencing Lucentis, for the treatment of retinal conditions.

Number 4: The China National Medical Products Administration (NMPA) approved Bio-Thera Solutions’ 

 (BAT1806) referencing Actemra for the treatment of several rheumatic conditions.

Number 3: Alvotech announced that a phase 1 pharmacokinetic study for its 

 for Celltrion Healthcare’s bevacizumab biosimilar (Vegzelma) referencing Avastin for the treatment of multiple forms of cancer.

 of biosimilars found that while the United States had significantly higher prices, the uptake in Germany and Switzerland, 2 European countries with national mechanisms for drug price negotiation, was slower.

The Top 5 Biosimilar Articles for the Week of January 16

Patent litigators from Fish & Richardson, an intellectual property law firm, regaled audiences during a webinar, entitled “

,” covering all the big biosimilar regulatory and legal decisions throughout 2022, including updates on patent disputes and anti-trust investigations.

Jenny Shmuel, JD, principal at Fish & Richardson, provided an overlook of the FDA approvals and US launches in the biosimilars space. During 2022, there were 7 

, including 1 for a high-concentration version of an adalimumab biosmilar (Hadlima; Organon/Samsung Bioepis), 4 launches, and 2 interchangeability designations (

). Additionally, there were 11 biologics license application (BLA) submissions for biosimilars.

Since the first quarter (Q1) of 2020, uptake of biosimilars has grown substantially for some molecules. Uptake for trastuzumab and bevacizumab biosimilars has grown from about 30% in Q1 2020 to around 80% in Q2 2022. For rituximab biosimilars, that number has grown from about 5% to 64% during the same time frame. However, uptake for pegfilgrastim, infliximab, and epoetin alfa biosimilars are still trying to catch up, only obtaining 42%, 42%, and 32% of the market share, respectively.

Shmuel highlighted the 13 big originator biologics that will lose exclusivity over the next 5 years (

), which is expected to face biosimilar competition starting in late 2023 or early 2024.

Throughout the year, there were 4 new patent lawsuits. According to Geoff Bieger, JD, principal at Fish & Richardson, this was lower than the peak of filings in 2018 (n = 12) but still up from 2021 (n = 3).

The cases ranged in how much the parties took part in the 

, a multistep process within the Biologics Price Competition and Innovation Act (BPCIA) that allows for both the originator company and the biosimilar company to exchange information relevant to the patents on the reference product that might be infringed by marketing of the proposed biosimilar.

Only 2 of the cases went through all steps of the patent dance process (Regeneron vs Mylan; Genentech vs Tanvex), 1 went through some of the steps (Biogen vs Sandoz/Polpharma Biologics), and the other went through none (Janssen vs Amgen) (

The Regeneron vs Mylan case resulted in a scheduled trial for June 12 through the 23 in 2023. The current standing of the Biogen vs Sandoz/Polpharma Biologics case is that the parties have jointly requesting for an expedited preliminary injunction proceeding. The Janssen vs Amgen case was filed in November 2022 and no patent dance steps have been taken so far. In the Genentech vs Tanvex case, the parties have demanded for a jury trial, which has not been scheduled yet.

Additionally, the Supreme Court is gearing up to weigh on the Amgen vs Sanofi case regarding Sanofi’s development of a PCSK9 antibody product. In December 2022, the Court granted certiorari, agreeing to review the 

, meaning whether a party that is “reasonably skilled” in a particular field could make or use an invention protected by a patent without “undue experimentation.”

“Although not a BPCIA decision, [this case] might have significant implications in the biosimilars context…" explained Bieger. "The question the Supreme Court has taken is whether or not section 112 requires the patent to teach how to make and use the full scope of the claim embodiments. More specifically, it requires a teaching to make and use all embodiments of the invention without substantial time and effort….The results in this one will definitely generate a lot of a lot of buzz in the coming year."

In August 2022, a case filed in March 2019 claiming that AbbVie, the maker of Humira (adalimumab), was engaging in anti-trust behavior by creating a 

 schemes to prevent biosimilar competition was dismissed. The court declared that “weak patents” are valid and protected under the Noerr-Pennington doctrine, rendering the patent thicket argument null and void. It also said that AbbVie allowing companies to launch their adalimumab biosimilars in Europe while holding off in the United States did not constitute as a pay-for-delay scheme.

A settlement for a case involving Pfizer’s infliximab biosimilar and Johnson & Johnson/Janssen’s patents for Remicade (reference infliximab) is in progress, with a fairness hearing scheduled for February 27, 2023.

Finally, the Federal Trade Commission (FTC) is continuing to investigate pharmacy benefit manager rebate contracts favoring reference products and whether they count as anticompetitive practices that hinder competition from biosimilars and generics.

“The FTC issued a statement on this in June 2022, and specifically identified rebates and fees that stifle competition from generics and biosimilars and increased costs,” Schmuel noted. "The FDA concluded in [a] statement that it will continue to scrutinize rebates and fees to see if antitrust laws have been violated, and will also monitor related litigation and file amicus briefs as necessary."

Patent litigators from Fish & Richardson, an intellectual property law firm, regaled audiences during a webinar covering all the big biosimilar regulatory and legal decisions throughout 2022, including updates on patent disputes and antitrust investigations.

Legal Experts Provide Updates on Biosimilar Patent Disputes in 2022

The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) granted 

, a ranibizumab biosimilar developed as part of a partnership between STADA Arzneimittel and Xbrane Biopharma.

The approval marks the second ranibizumab biosimilar for the UK market, following the approval of Teva Pharmaceuticals’ 

Ranibizumab products are vascular endothelial growth factor inhibitors used for the treatment of retinal diseases, such as neovascular age-related macular degeneration (AMD), macular edema, diabetic retinopathy, retinal vein occlusion, and visual impairment due to choroidal neovascularization in adults. Ximluci was approved for all indications of the reference products.

“Considerable unmet need for biologic ophthalmic treatments exists in the UK and throughout Europe…. With almost 15 years’ experience of supplying biosimilars, STADA looks forward to working with Xbrane, as well as with the [National Health Service] and our commercial partners, to broaden patient access to ranibizumab and optimize use of healthcare resources in the UK,” commented Bryan Kim, MBA, head of specialty care at STADA Arzneimittel.

, nearly 1.5 million people in the United Kingdom have macular disease and it affects people of all ages, especially people older than 55 years. AMD is the most common cause of vision loss in the United Kingdom and impacts more than 600,000 people.

“We are proud to have worked with STADA to take this molecule, developed under the Xlucane name, from cell-line development to approval and manufacturing, based on our patented expression system in Europe,” said Martin Åmark, MSc, MBA, CEO of Xbrane Biopharma.

The approval for Ximluci was granted through the European Commission (EC) Decision Reliance Procedure, whereby the MHRA’s decision was based on the one made by the EC. The EC granted marketing authorization to Ximluci in 

, making it available for patients in all 27 European Union member states, Iceland, Norway, and Liechtenstein. The EC came to its decision after reviewing data establishing Ximluci’s biosimilarity to the refence product. Ximluci was the third ranibizumab biosimilar to be approved in the European Union, following the approvals for 

STADA Arzneimittel and Xbrane Biopharma entered into a 

, in which both companies share development and manufacturing responsibilities. STADA Arzneimittel, a Bad Vilbel, Germany–based company, holds the marketing authorizations and commercial rights for the biosimilars included in the deal across all territories, including Europe, the United States, and several countries in the Middle East and North Africa, as well as markets in the Asia-Pacific region.

The United Kingdom has approved STADA Arzneimittel and Xbrane Biopharma’s Ximluci, a ranibizumab biosimilar referencing Lucentis, for the treatment of retinal conditions.

UK Authorizes New Lucentis Biosimilar, Ximluci

Health Canada has granted approval for Celltrion Healthcare’s bevacizumab biosimilar, Vegzelma, for the treatment of multiple forms of cancer, according to a 

The biosimilar represents the fifth bevacizumab biosimilar and fiftieth biosimilar approval in Canada. The other bevacizumab biosimilars include Abevmy, Aybintio, Bambevi, Mvasi, and Zirabev. It is also the second Canadian approval in 2023, following the approval of Samsung Bioepis and Organon’s high-concentration, citrate-free formulation of 

, an adalimumab biosimilar referencing Humira.

Vegzelma, also known as CT-P16, referencing Genentech’s Avastin. Bevacizumab products are inhibitors for vascular endothelial growth factor receptors. The drug is used in the treatment of metastatic colorectal cancer, non-small cell lung cancer, epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and glioblastoma. Vegzelma was approved for all the same indications as the reference product.

 Vegzelma as the United States’ fourth bevacizumab biosimilar in September 2022. In August 2022, the European Commission gave its decision 

granting Vegzelma marketing authorization

 throughout the European Union. Overall, Vegzelma is approved in 35 countries, including the Republic of Kora, the United Kingdom, and Japan.

“We hope that Vegzelma, the third anti-cancer antibody biosimilar after Truxima and Herzuma, will settle quickly in the Canadian market…. We will do our best to supply high-quality biopharmaceuticals at reasonable prices to provide various treatment options to patients at home and abroad,” a Celltrion representative said.

In January 2023, Celltrion signed an agreement with Hikma Pharmaceuticals for the commercialization of Vagzelma in 17 countries throughout the Middle East and North African region., including Jordan and Morocco, according to 

. It would be the sixth drug developed by Celltrion to be distributed by Hikma in the region, a list which includes Truxima (rituximab biosimilar), Remsima (infliximab biosimilar), and Herzuma (trastuzumab biosimilar).

Prior to the approval, Celltrion announced the submission of a biologics license application for the American approval of its infliximab biobetter, 

. The biobetter references the company’s infliximab biosimilar (Remsima), which references Remicade, and is the only infliximab product in the world that allows for subcutaneous administration.

Additionally, KoreaBioMed reported that in early 

, Celltrion signed an development deal with Rani Therapeutics over an oral formulation of the former’s ustekinumab (CT-P43) biosimilar for the treatment of psoriasis, plaque psoriasis, psoriatic arthritis, Crohn disease, and ulcerative colitis. The development would leverage Rani Therapeutics’ 

, which could allow for the oral administration of any drug, including large molecules.

Health Canada has granted approval for Celltrion Healthcare’s bevacizumab biosimilar (Vegzelma) referencing Avastin for the treatment of multiple forms of cancer.