Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 Biosimilar Articles for the Week of April 15

 Data from 2021 and 2022 showed that biosimilar use within an 

 was on the rise, suggesting that the country could achieve total utilization in the coming years. The researchers touted the growing success, saying that more use will benefit the National Health System (NHS) and citizens who rely on an efficient and sustainable health care policy.

 Sarfaraz K. Niazi, PhD, outlines the current state of 

 in the US and policy changes needed to clear up misconceptions surrounding the meaning behind interchangeability designations.

 evaluating IQVIA data found that rebate schemes orchestrated by pharmacy benefit managers (PBMs) are costing US patients and payers billions of dollars by suppressing biosimilar adoption.

 is projected to surge from $25.1 billion in 2022 to approximately $1.3 trillion by 2032, with a compound annual growth rate of 17.6%, driven mainly by the increasing prevalence of cancer and the cost-effectiveness of biosimilars, as outlined in a report by Towards Healthcare.

 After poor sales for its adalimumab biosimilar, Boehringer Ingelheim (BI) announces layoffs; Teva Pharmaceuticals and mAbxience 

; Samsung Bioepis begins a phase 3 trial for a biosimilar referencing Keytruda (pembrolizumab).

To read all of these articles and more, visit 

Videos

Here are the top 5 biosimilar articles for the week of April 15, 2024.

Illustration of biosimilar medicines | Image Credit: TarikVision - stock.adobe.com

The combination of sintilimab, a low dose of bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) showed promising efficacy and safety in treating patients with unresectable hepatocellular carcinoma (HCC).

Researchers at the Tianjin Medical University Cancer Institute and Hospital in China conducted a 

The trial involved patients with HCC who hadn't undergone any prior systemic therapy for their cancer. From May 2021 to October 2021, the enrolled patients received a combination treatment of sintilimab (200 mg), IBI305 (7.5 mg/kg), and HAIC (folinic acid, fluorouracil, oxaliplatin for 23 hours) every 3 weeks.

Primary endpoints were the objective response rate (ORR), mainly based on the pathologic results of patients after surgical treatment with the drug, and the treatment-related adverse events (TRAEs). Secondary endpoints included the event free survival (EFS), overall survival (OS), the pathological complete response (pCR) rate, and the surgical conversion rate. Researchers observed disease control in patients with partial responses (PR) and stable disease (SD).

The patients that reached conversion surgery criteria were administered another cycle of sintilimab and HAIC. Contrast-enhanced computed tomography or magnetic resonance imaging were used to assess tumors at baseline and after the third to the sixth cycle of treatment to evaluate resection probability.

A total of 30 patients were enrolled in the study with their safety outcomes analyzed. After 1 voluntarily withdraw, 29 patients completed antitumor efficacy outcomes, conversion therapy, and the tumor assessments.

Participants had a median age of 55.5 years, included 26 males (72.2%), over a 3-cycle treatment duration period. The study population consisted of 79.3% of patients with hepatitis B and 13.8% with hepatitis C. The most common observations made among patients were vascular invasion (51.7%) or extrahepatic metastasis (48.3%).

Results met the primary endpoint with 17 (58.6%) of 29 unresectable HCC patients that were assessed by an independent review committee achieved ORR. About 23 of 29 patients observed disease control with partial response (PR) in 17 (58.6%) patients and stable disease in 6 (20.7%). Following conversion treatment, a-fetoprotein levels decreased (

Among 20 patients, further treatment was successfully converted (69%). Although, 1 patient refused further treatment and 19 patients were included in the final count. Tumor remission status of 14 patients underwent resection, 3 underwent radiofrequency ablation, 2 underwent biopsies to compare treatment effects, and all patients achieved R0 resection. Only 1 patient (5.3%) achieved pCR and 5 patients (26.3%) reached major partial response after undergoing pathological examinations using surgical specimens or biopsy specimens.

On average, follow-up ranged over 19.3 months. The OS rate of the 29 patients after 3, 6, 9, and 12 months was 93.1%, 86.2%, 72.4%, and 65.5%, respectively. The EFS rates for 3, 6, 9, and 12 months were 89.7%, 62.1%, 44.8%, and 41.4%.

Clinical remission was achieved by 1 group of patients while another group achieved SD or PR. After 1 year, OS rates of the PR group (n =17) and PD plus SD group (n =12) were 82.4% and 41.7%. After 1 year, EFS rates of the PR group and PD plus SD group were 52.9% and 25%.

The most common TRAEs included thrombocytopenia (40%), hypertension (23.3%), leukopenia (23.3%), hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). There were no serious adverse events (AEs) detected.

Study limitations include doses of treatment because fewer AEs could have occurred with lower medication doses. As a result of AEs, patients had poor compliance with treatment.

Results suggest that sintilimab combined with bevacizumab biosimilar and HAIC could be an effective and well-tolerated treatment for patients with unresectable HCC. However, larger studies are required to solidify these findings and determine its wider use in the future.

Liu D, Mu H, Liu C, et al. Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial. 

. 2024;70(06):811-818. doi:10.4149/neo_2023_230806n413

Articles

Positive results of sintilimab, IBI305, and hepatic arterial infusion chemotherapy (HAIC) treatment showed shrinking tumors and previously converting inoperable hepatocellular carcinoma (HCC) to resectable HCC with manageable adverse effects.  

Sintilimab, Bevacizumab Biosimilar, HAIC Improves Survival in Patients With Unresectable HCC

The Top 5 Videos for the Week of April 8

 A systematic review and meta-analysis of 7 randomized controlled trials found 

 in efficacy and safety indicators between adalimumab biosimilars and the reference product (Humira) for treatment of moderate to severe psoriasis.

 A Chinese company has expressed interest in developing a 

 (semaglutide), a popular drug used for diabetes and weight loss; Biocon and Mylan are in talks to merge their biosimilar businesses; Celltrion completed its biologic license application (BLA) for its omalizumab biosimilar candidate.

 Although tender systems are a common strategy to encourage biosimilar utilization across Europe, policies like automatic substitution are rarely utilized, according to a systematic review of 

Sarfaraz K. Niazi, PhD, outlines how President Joe Biden's 

 could impact biosimilars, including provisions to clear up confusion surrounding interchangeable products.

Here are the top 5 biosimilar articles for the week of April 8, 2024. 

The Top 5 Biosimilar Articles for the Week of April 8

Ha Kung Wong, JD.

In an interview with The Center for Biosimilars

, Ha Kung Wong, JD, an intellectual property attorney and partner at 

, dives into the advantages of the patent dance. Wong, a specialist in intellectual property law, explores how this process streamlines information exchange and minimizes unnecessary lawsuits.

The patent dance, Wong explains, establishes a framework for early disclosure of patents and potential infringement concerns between biosimilar developers and reference product sponsors. By enabling early assessment of patent validity and infringement, it empowers parties to reach settlements before product launch, saving both time and money.

This approach mirrors the Hatch-Waxman Act for traditional drugs and has demonstrably reduced litigation in the biosimilar space. Even when lawsuits become necessary, the patent dance helps focus on the most critical patents, minimizing resource expenditure for all involved.

What are the key objectives of the patent dance, and how does it contribute to streamlining the exchange of information while reducing the potential for wasteful litigation?

The patent dance allows for an early assessment of infringement and validity patient positions, even before the filing of a litigation and that can help parties reach an early settlement.

Part of the process here is don't slow down biosimilar approval process, don't subject them to damages from launching at risk. Let's resolve all the patent issues in advance or at the time in which you're looking to get approval, such so that you can get it resolved at the time you get approval.

If you don’t have a problem with the patents, then you can launch without any risk and you're okay. If you do, let's sort that out.

 does for small molecules and that's what this 

 [Biologics Price Competition and Innovation Act] patent dance does for biosimilars and it's been really effective.

I think it’s led to a great number of settlements, very few of them go to trial, which means we're not wasting resources on litigation. As much as I do litigation, so I like to have litigation, I think for my clients, it's a win-win all the way around.

Also, the case management mechanisms have been very effective at limiting the size of the litigations. For example, in the recently decided 

 relating to Eylea, despite 24 patents initially being asserted, the case was initially narrowed to set 6 patents, and then further narrowed to 3 patents for an expedited trial that provided the companies with resolution.

One patent was found valid and infringed without having to litigate all the asserted patents. I think, by and large, it’s working to really save resources for all parties involved. If it has to go to litigation, it goes but it also is resulting in favorable settlements in which everybody wins.

Intellectual property attorney Ha Kung Wong, JD, describes the patent dance and how it is designed to streamline information exchange while avoiding unnecessary lawsuits by allowing early assessment of patent infringement and validity.

Streamlined Approach to Biosimilar Approval Reduces Litigation Risk

The Top 5 Biosimilar Articles for the Week of April 1

 described the totality of evidence supporting the approval of the adalimumab biosimilar AVT02 (Simlandi; Alvotech) for all approved indications of the reference product, Humira.

 Sarfaraz K. Niazi, PhD, outlines how President Joe Biden's 

The Association for Accessible Medicines’ 

 on Medicare Part D tiering revealed low coverage rates for insulin and adalimumab biosimilars across plans.

 reintroduce the Increasing Access to Biosimilars Act, a bipartisan bill aimed at boosting competition and encouraging providers to prescribe biosimilars, to Congress.

Despite more biosimilars entering the market and generating significant savings for payers and health care systems, these savings are not resulting in lower 

 for patients, according to a recent study.

Here are the top 5 biosimilar articles for the week of April 1, 2024.

The Top 5 Biosimilar Articles for the Week of March 25

 A real-world study surveying physicians and patients on adalimumab biosimilar ABP 501 (Amgevita) in inflammatory bowel disease (IBD) found both patients initiating 

 and those who had switched from the reference product had higher satisfaction levels.

Sarfaraz K. Niazi, PhD, explains how the new 

 under the Medicines and Healthcare Products Regulatory Agency (MHRA) could expand biosimilar access within the United Kingdom, in his latest column.

Senators Michael Bennet (D-Colorado) and John Cornyn (R-Texas) have reintroduced the 

Increasing Access to Biosimilars Act to Congress

 is to boost competition and increase incentives for providers to prescribe biosimilars over their more expensive reference agents.

 presented at the American Academy of Dermatology (AAD) annual meeting examined the effects of switching from reference ustekinumab and adalimumab to biosimilar versions in patients with different types of psoriasis.

 7% overall last year, including a 15% spike in biosimilar sales, according to the company’s 

 for the fourth quarter (Q4) and full year (FY) 2023.

Here are the top 5 biosimilar articles for the week of March 25, 2024. 

Inflamed areas affected by rheumatoid arthritis  | Image Credit: peterschreiber.media - stock.adobe.com

Patients with rheumatoid arthritis (RA) that did not respond well to methotrexate experienced no difference in efficacy, safety, immunogenicity, or pharmacokinetic (PK) profiles when they switched to the proposed tocilizumab biosimilar, BAT1806/BIIB800.

phase 3, multicenter, randomized, double-blind, active-controlled, equivalence study

 conducted from December 19, 2018, to January 5, 2021, examined participants in a 24-week initial treatment period followed by a 24-week secondary treatment period (48 weeks). Patients were recruited from 54 centers across China, Ukraine, Poland, Georgia, and Bulgaria.

Participants were assigned at random through a computerized, interactive, web-response system to receive reference tocilizumab up to week 48, reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48, or BAT1806/BIIB800 up to week 48.

Study demographics were similar between originator tocilizumab and biosimilar BAT1806/BIIB800 (n = 309, 312, respectively). Both groups had a majority of White, female participants from central Europe.

Medication was administered once every 4 weeks at an 8 mg/kg dose by a 1-h intravenous infusion up to and including week 20. A stable 10 to 25 mg dose of methotrexate therapy per week continued among all participants. The Disease Activity Score in 28 joints (DAS28) and individual response rates based on the American College of Rheumatology (ACR) were utilized as study resources.

Aside from RA, common conditions among patients were hypertension, menopause, osteoporosis, and anemia (26%, 13%, 10%, 9%). Treatment period 1 was completed by 93% of participants in both the reference and tocilizumab biosimilar group.

The primary endpoint was measured as the proportion of participants with a 20% (ACR20) improvement based on the ACR criteria by week 12 or 24. An estimated proportion of participants with an ACR20 response were 64.8% in the reference group and 69.0% in the biosimilar at week 12 and 67.9% in reference group and 69.9% in biosimilar group at week 24. The estimated difference between ACR20 response rates was 4.1% at week 12 and 1.9% at week 24. Both groups consisted of comparable PK and immunogenicity profiles.

From baseline to week 24, neither group expressed major differences in proportions of ACR20, ACR50, ACR70 or in the number of respondents over time. Baseline reductions were similar in the DAS28-erythrocyte sedimentation rate and DAS28-C–reactive protein among groups.

A total of 407 participants experienced about 1340 adverse events (AEs) throughout treatment period 1, mainly of mild severity. The reference group consisted of 151 patients with treatment emergent adverse events (TEAEs) and 140 patients made up the BAT1806/BIIB800 group. Infections were the most common serious TEAEs, reported in 5 of the participants in the reference group and 3 of the patients taking BAT1806/BIIB800. Only 1 fatal event was reported as potentially related to the medications.

Safety profiles of reference tocilizumab and BAT1806/BIIB800 were comparable but had lower risk of infections in the biosimilar group. No meaningful differences in PK among treatment groups were measured by serum trough levels with variability observed in both groups.

Study limitations were caused by the majority of European women enrolled in both groups without including radiographic assessments as a measure of disease progression.

Patients with RA that had inadequate responses to methotrexate expressed equivalent efficacy of BAT1806/BIIB800 to the EU-sourced reference tocilizumab over a 48-week treatment period with the COVID-19 pandemic concluding little to no effect on the study conduct.

Leng X, Piotr Leszczyński, Jeka S, et al. Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial. 

. 2024;6(1):e40-e50. Published Online Feb. 5, 2024. doi:10.1016/s2665-9913(23)00237-0

Switching to the biosimilar version of tocilizumab (BAT1806/BIIB800) showed similar effectiveness, safety, and tolerability compared with the original drug for patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate.

Switch to Biosimilar BAT1806/BIIB800 Maintains Efficacy, Safety in Patients With RA

In 2023, STADA Arzneimittel’s group adjusted sales were up by 14% with a 19% improvement rate in earnings before interest, taxes, depreciation, and amortization (EBITDA), according to the company’s annual 

. Overall, 2023 sales were around $4 billion and $870 million in the annual EBITDA. Additionally, the company had a total of 95 business development and licensing deals signed in 2023.

This past November, about 91% of STADA colleagues voluntarily participated in a global employee survey on various industry benchmarks, which exceeded expectations. Around 88% of the survey participating employees expressed confidence towards the company’s successful business objectives.

Peter Goldschmidt, CEO of STADA, claimed, “Our performance continues to progress ahead of major competitors. Our culture with entrepreneurial focus is delivering new launches from our extensive pipelines, on top of strong organic growth.”

Specialty was STADA’s fastest growing product segment in 2023 and hit a company milestone as it entered the European ophthalmology market. A 25% increase in sales was achieved, leading to a total of around $8 million dollars. STADA’s sixth marketed ranibizumab biosimilar (Ximluci), is an alternative to the reference brand Lucentis (ranibizumab). Previous launches of similar biologics include Hukyndra (adalimumab biosimilar), Oyvas (bevacizumab biosimilar), and Movymia (teriparatide).

The Consumer Healthcare product segment by STADA largely drove the sales growth up in 2023, accounting for 40% of the total Group sales. Goldschmidt’s claims were supported by the company’s outperformance against other top competitors as their sales advanced up to $1.6 billion, a 17% increase.

This success has awarded STADA Europe’s fourth largest Consumer Healthcare supplier in sales. Grippostad, Silomat, Multilind, Elotrans, and Hoggar were among some of the brands that had the ability to grow significantly, establishing market leadership in Germany. In conjunction with Germany, Belgium, France, Italy, and Spain had improvements in Consumer Healthcare market positions too.

In July 2023, STADA acquired the brands known as Antistax (red-vine-leaf-extract), Lomudal (chromoglycate sodium), Omnivit (carbonyl iron, folic acid, zinc sulfate, vitamin B complex, vitamin C), and Opticrom (cromolyn sodium ophthalmic solution) from Sanofi. This status elevated STADA’s partnership appeal as they continue to build upon their existing commercialization throughout 20 European countries.

Generics were a major contributor to the 6% increase in sales, with STADA earning $1.6 billion. Launches assisting in this progress include anticoagulant apixaban, the diabetes drug sitagliptin, analgesic tapentadol, and medications that reverse the effect of muscle relaxants known as tacrolimus for transplantation and sugammadex.

Annual sales for Stelara are around $2.7 billion in Europe but STADA’s ustekinumab biosimilar, Uzpruvo, introduced competition after it received positive attributes for the first time by the European Medicines Agency. By the end of 2023, an increasing number of patients in Germany began Kinpeygo (budesonide), the first treatment approved in Europe for rare kidney diseases.

An improved independent assessment of the Group’s environmental, social, and governance (ESG) risk was reflected in December 2023. STADA was ranked as the top 6% of global pharmaceutical companies when considering ESG. An assessment compared STADA with 900 other global pharmaceutical companies and expressed their dedication to working as a trusted partner with society, customers, regulators, and capital market stakeholders to ensure success.

Goldschmidt concluded the expense report, “With our unique culture driving performance, I am confident that we have the team, the products, and the pipeline in place to maintain our strong growth momentum.”

Germany-based biosimilar manufacturer STADA Arzneimittel reports strong financial performance in 2023 with double digit sales growth and billions in profits. The CEO credits the company’s success on their strong company culture and focus for innovation. 

Annual STADA Report Shows Record Profit Growth for 2023

Ha Kung Wong, JD on antitrust lawsuits

, intellectual property lawyer, Ha Kung Wong, JD, partnered with 

, discusses the impact of lawsuits on biosimilar accessibility. He mentions a recent lawsuit by Johnson & Johnson (J&J), aiming to delay biosimilar competition and other relevant legal cases.

Wong points out that antitrust suits targeting biosimilar competition are not uncommon, especially for expensive drugs. He then elaborates on 3 past lawsuits: J&J’s antitrust suit regarding Remicade (reference infliximab), the Remicade exclusionary contracting lawsuit by Pfizer, and the lawsuit regarding Humira (reference adalimumab).

While these lawsuits might have discouraged the use of exclusionary contracts, their effectiveness remains debatable due to relatively small settlements compared to the drugs' revenue. The interview concludes surrounding the uncertainty of future lawsuits' and the impact they have on biosimilar accessibility.

Recently, CareFirst BlueCross BlueShield filed a lawsuit against J&J alleging that the company is “scheming” to delay ustekinumab biosimilar competition. How do you expect this case to play out and what impact could it have on the overall biosimilar industry?

This is not the first antitrust suit to be filed related to a biosimilar and biosimilar competition, particularly on drugs that are costly so it really isn't surprising to see another antitrust suit.

As a side note, talking about antitrust always reminds me of the 2001 movie 

 starring Ryan Phillippe and Rachael Leigh Cook, but I digress.

Previous antitrust suits, you know that I think we want to think about in conjunction with this one would be the 

Remicade exclusionary contracting class action lawsuit

. That actually was settled by consumers, third party payers for $25 million.

Remicade exclusionary contracting lawsuit by Inflectra

 biosimilar manufacturer, Pfizer. There was an undisclosed settlement agreement there.

, which found that filing numerous patent applications was a form of petitioning the government, qualified for Noerr-Pennington immunity and that protects the filing under the First Amendment petition and free speech clause.

Even if the petition is anticompetitive, it's immune from antitrust action. I bring those up because so far, the biosimilar antitrust suits may have had some positive impact on decreasing the usage of exclusionary contracts to prevent biosimilar formulary coverage.

However, it's yet to be seen maybe debatable how steep of a deterrent something like a $25 million settlement is on a drug similar to Remicade, which is making over $6 billion a year.

It’s unclear whether another antitrust lawsuit will have a significant impact on biosimilars going forward or not. But certainly something that we should keep an eye on and certainly something we should be vigilant about.

Ha Kung Wong, JD, an intellectual property attorney, discusses lawsuits by drug companies aimed at delaying competition from biosimilars, but the effectiveness of these lawsuits in hindering biosimilar access remains uncertain.

Antitrust Lawsuits on Increasing Biosimilar Accessibility

The Top 5 Biosimilar Articles for the Week of March 18, 2024. 

 from Association of Cancer Care Centers 50th Annual Meeting and Cancer Center Business Summit (AMCCBS) and the American Academy of Dermatology (AAD) highlight the benefits of incorporating biosimilars into electronic medical records and the biggest barriers for home injection of biologics.

 A review looking back at the last 15 years of experience with the 

 (Zarxio) provides a detailed overview on how filgrastim biosimilars came to be and the evidence behind why oncologists have come to accept them as standard practice.

 In its earnings report for the fourth quarter and full year of 2023, 

 detailed its rising revenue growth, which it partly attributed to increased sales for its pegfilgrastim and ranibizumab biosimilars.

 Kashyap Patel, MD, CEO of Carolina Blood and Cancer Care, a member of the Community Oncology Alliance, and member of The Center for Biosimilars® Advisory Board, glances back at the development of the 

 was reported to be as safe and effective as the reference product in a review of randomized controlled trials and real-world studies on immune-mediated inflammatory diseases.

Here are the top 5 biosimilar articles for the week of March 18, 2024. 