Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

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

Articles

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

In an interview with The Center for Biosimilars

, 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.

Videos

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.

To read all of these articles and more, visit 

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

The Top 5 Biosimilar Articles for the Week of March 18

Blood sample for growth hormone test | Image Credit: Saiful52 - stock.adobe.com

Omnitrope, a biosimilar somatropin, which is a recombinant of human growth hormone (rhGH), expressed effective and well tolerated treatment in pediatric patients.

The EMA approved Omnitrope in 2006 as their first biosimilar approval. Recombinant human growth hormone replacement therapy is often used to treat children born small for gestational age (SGA), Turner Syndrome (TS), children with idiopathic short stature (ISS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), and Noonan syndrome. The FDA has also approved Omnitrope, however, because it was approved before the establishment of the biosimilars approval pathway, it is not legally considered a biosimilar in the US.

pediatric patients treated with Omnitrope (PATRO) trial

 was an observational, multicenter, international, longitudinal study. Patient data were included in electronic case report forms that were completed at each routine visit and were entered into a web-based electronic data collection system.

Data collection went from September 1, 2007 to July 23, 2020. Eligible patients included a total of 7359 male or female infants, children, or adolescents who received biosimilar rhGH. Patients enrolled from 304 different sites among 15 countries.

At baseline, the study included more male participants than female participants (59.1% vs 40.9%). Collectively, growth hormone deficiency was the most common indication treatment was necessary, along with SGA (57.9% and 26.6%, respectively). Almost all patients were treatment-naïve at baseline (86%).

The standard deviation (SD) of exposure to biosimilar rhGH was 3.66 years (GHD: 3.56 years; TS: 3.54 years; CRI: 2.77 years; SGA: 3.86 years; PWS: 4.97 years; ISS: 3.22 years; other: 3.66 years).

Treatment discontinuation was primarily due to patients reaching adult height or bone age maturity (12.1%). Adverse events (AEs) were the main reason for discontinuation of treatment in 140 patients (1.9%), followed by lost to follow-up, site closure, or the patient reached near-adult height (8.1%, 8%, 8%, respectively).

There were 835 AEs in 614 patients and 113 serious adverse events (SAEs) found among 84 patients, likely related to biosimilar rhGH. Headache, injection-site pain, injection-site hematoma, and arthralgia were among the most common AEs but only affected a small number of patients. Hypothyroidism and sleep apnea syndrome, reported in less than 1% of patients, were the most frequent SAEs suspected to be a reaction to the medication.

The incidence rate (IR) for developing type 1 diabetes mellitus (T1D) or T2D was 0.11 per 1000 person-years (PY), across all indications. In patients born SGA, the IR for developing T2D was 0.13 per 1000 PY and 0.86 per 1000 PY in patients with PWS. Newly developed malignancies had an IR of 0.26 per 1000 PY across all indications with 0.22 primary malignancies per 1000 PY across all patients.

In as early as 6 months, both treatment-naïve and pretreated patients expressed treatment effectiveness among 6589 patients with sustained catch-up growth observed across all indications. Treatment-naïve patients had a median (range) height score increase from baseline by a median range of 0.65 (–1.5 to 3.3) at 1 year and 1.79 (–3.7 to 6.2) after 5 years. Pretreated patients had an SD score increase from baseline by a median range of 0.24 (–3.8 to 2.9) at 1 year and 0.73 (–1.4 to 3.7) after 5 years.

The study was limited by the likelihood of missing data that risks alternative results and potential conclusions. Assessments and laboratory tests were led locally instead of centrally, which could create variations among centers. Lastly, with some AEs, like malignancies, developing over several years, the patient follow-up period should be studied further.

Authors conclude the study offers, “additional reassurance to health care professionals and patients that these agents are as effective and well tolerated as others, thus widening patients’ access to life-changing treatments worldwide.”

Loche S, Kanumakala S, Backeljauw P, et al. Safety and effectiveness of a biosimilar recombinant human growth hormone in children requiring growth hormone treatment: Analysis of final data from PATRO children, an international, post-marketing surveillance study. 

. 2024;18:667-684. doi:10.2147/DDDT.S440009

A large-scale study found that Omnitrope, a biosimilar growth hormone, is effective and well-tolerated in treating various growth disorders in children.

Biosimilar Growth Hormone Reveals Efficacy, Safety in Real-World Pediatric PATRO Study

The Top 5 Biosimilar Articles for the Week of March 11, 2024. 

 analyzing 3 years of treatment patterns for patients with Crohn disease on biologics found that while more patients received infliximab, adalimumab, and vedolizumab initially, ustekinumab showed the highest persistence and lowest dose escalation rate, indicating potentially better clinical response compared to other biologics.

provided updates on how provider acceptance growth, evolving payer dynamics, and the growing pipeline for biosimilars will shape the biosimilar landscape over the next 5 years.

 (Tyenne; tocilizumab-aazg), making it the second tocilizumab biosimilar overall and first tocilizumab biosimilar to be approved with both intravenous and subcutaneous administration options.

Sarfaraz K. Niazi, PhD, takes a look at the 

European Medicines Agency's (EMA) announcement

 that it will investigate whether comparative efficacy tests should be needed for a biosimilar to receive regulatory approval.

 (denosumab-bddz; GP2411), the first biosimilar to reference Xgeva/Prolia (denosumab) in the US.1 The drugs will be used to treat osteoporosis and hypercalcemia as well as prevent skeletal-related events associated with bone metastases from solid tumors.

Here are the top 5 biosimilar articles for the week of March 11, 2024. 

The Top 5 Biosimilar Articles for the Week of March 11

Patient treated with chemotherapy | Image Credit: NDABCREATIVITY - stock.adobe.com

A combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited efficacy and favorable safety as second and beyond line therapy in patients with HER2-positive metastatic breast cancer.

From March 2020 to December 2021, a Beijing Cancer Hospital held a 

prospective, single-arm, single-center, phase 2 clinical trial.

 Eligible participants included patients diagnosed with metastatic breast cancer who were previously treated with trastuzumab alone but experienced disease progression during or after therapy.

Based on the physician, patients were assigned trastuzumab (HLX02), pertuzumab and chemotherapy at baseline. Trastuzumab (HLX02) was administered intravenously as an 8 mg/kg loading dose followed by 6 mg/kg maintenance doses every 3 weeks. Pertuzumab was administered intravenously as an 840 mg loading dose followed by 420 mg maintenance doses every 3 weeks.

Every 6 weeks, tumor assessment was computed with a tomography scan of the chest and if the disease progressed after 6 months, the investigator made the decision on whether to continue chemotherapy or not. Trastuzumab and pertuzumab continued to be administered until disease progressed or toxicity became intolerable to patients.

Study results found treatment was well tolerated among participants. A total of 45 patients were included in the data with a median age of 56 years. Of the total number of patients, 12 (26.7%) were treated in second line, while 33 (73.3%) were treated in third line and later settings.

The primary endpoint of the study was the progression free survival (PFS), which was calculated from the time of first administration to the time of disease progression or death. Follow-up consisted of an average of 24.4 months, with 35 of the 45 patients enduring PFS events for about 7.6 months. There were no major differences observed in the subgroup analysis for PFS.

Overall survival, a secondary endpoint of the study calculating the time of the first administration to the time of death due to any cause, was unable to be reached due to the short follow-up period.

Another secondary endpoint of the study, objective response rate (ORR), was defined as the proportion of patients with measurable disease whose best overall response was evaluated as either complete remission (CR) or partial remission (PR). At the end of the study, 14 (31.1%) patients achieved PR, 27 (60%) had stable disease, and 4 (8.9%) had progressive disease. None of the patients had a CR.

Lastly, the disease control rate (DCR) was a secondary endpoint defined as the proportion of patients who achieved CR, PR, and stable disease (SD). Patients achieved a 31.1% ORR with a 91.1% DCR.

The safety profile of the treatments found most toxicities were grade 1 or 2 and manageable. The most common adverse events were neutropenia (n = 20 patients; 44%), anemia (n = 9; 20%), diarrhea (n = 9; 20%), and alanine aminotransferase/aspartate aminotransferase elevation (n = 8; 17.8%).

Adverse events graded a 3 or higher, mainly neutropenia patients (n = 3; 6.7%), were ruled to mainly be associated with chemotherapy instead of trastuzumab or pertuzumab. Overall, the study regimen did not exhibit any unexpected toxicities.

The study's main limitation was the single arm, single center study design. Additionally, the follow-up period was not long enough to allow for an overall survival analysis.

Authors concluded that their findings provide new evidence for treatment of dual-antibody therapy in late-line settings of patients with HER2-positive metastatic breast cancer.

Zhang R, Liu X, Song G, Zhang Y, Li H. Trastuzumab biosimilar (HLX02), pertuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer after progression of trastuzumab: A prospective, phase II study. 

. Published online December 20, 2023. doi:10.4143/crt.2023.1151

A study found combining trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy was effective and safe for patients with HER2-positive metastatic breast cancer who progressed after prior trastuzumab therapy.

HLX02, Pertuzumab, Chemotherapy Combination Effective, Safe in Advanced HER2-Positive Breast Cancer

Biosimilars Versus Bad Patents: Accessibility, Key Court Cases With Ha Kung Wong, J.D.

Ha Kung Wong, JD, an intellectual property attorney specializing in intellectual property law partnered with 

, discusses the patent system and biosimilar accessibility in an interview with The Center for Biosimilars

. He acknowledges concerns regarding "bad patents" that could limit access to biosimilars but expresses confidence that the FDA and 

 [United States Patent and Trademark Office] will refine the system to only grant good patents.

Wong highlights specific court cases involving biosimilars, including 

. He advises stakeholders to follow these cases as they may have a significant impact on the biosimilar market. Despite the challenges of bad patents, Wong assures us that biosimilars are continuing to enter the market and driving down health care costs.

How does the patent system impact biosimilar accessibility and how can it be improved to better balance investor interests and the need for more affordable health care options?

By and large, the patent system is really no different with respect to biosimilar accessibility, as it is to small molecule accessibility or any other areas of life sciences.

As outlined in the Constitution, good patents help protect innovation, which in turn provides incentive for development of new life saving treatments, as well as disclosure of information to promote continued development of those treatments. The problem we have is that not all patents are good, right? There are bad patents and they can be impactful in terms of limiting health care options.

The FDA and the USPTO [United States Patent and Trademark Office] have been collaborating to provide a more robust patent system for pharmaceutical patents and more robust in terms of making sure good patents come out and not bad patents.

For instance, they propose more training and time for patent examiner's during prosecution, better examination means better patents, and they have encouraged increased disclosure of regulatory materials during prosecution.

This proposal could help to avoid patents being issued that should not be either based on not properly meeting the patentability requirements or by inappropriately overlapping with earlier issued patents, which could in turn lower the number of bad patents that biosimilars would have to contend with.

That being said, the patent system as is hasn't necessarily negatively impacted biosimilar accessibility. Biosimilars are getting to the market and are bringing prices down and providing more affordable health care, even when they don't necessarily capture large market shares.

According to the quarter for 2023 report by 

, the average sales price declined on average of 41% 3 years post-biosimilar launch and over 50% in the oncology space. There's a lot of benefit here from biosimilar launches and patents aren't necessarily stopping that from happening but we should be vigilant about bad patents. We don't want those to be allowed.

We’re starting to see some of the settlements for patent cases involving ustekinumab biosimilars as well as new cases regarding aflibercept biosimilars. What other biosimilar court cases should stakeholders be watching?

Well, there are a number of them and keep in mind that a lot of these biosimilars cases are fact specific so they won't necessarily result in something that will have wide ranging impact on the industry. But I do think there are a couple that we should keep an eye on.

First of all, Eylea has 5 pending lawsuits, a number of pending 

aBLAs [abbreviated Biologics License Applications

]. This is definitely going to be a drug to watch in terms of decisions and market impact.

Solaris, they had a first litigation related to the proposed Solaris biosimilar, SB12, which was just filed on January 3 of this year by 

 and again Samsung Bioepis. Samsung Bioepis provided its 180 day notice of commercial marketing over 6 months ago in July of 2023, which means it could launch at risk at any point after receiving FDA approval. It was a pending aBLA that was accepted by the FDA by July of 2023 so it's possible that launch could be soon if Alexion doesn't request supplementary injunction.

There's a lot of things here, a lot of moving parts here that we want to keep an eye on to see how that impacts the process when which a biosimilar might go through if they want to be aggressive and launch at risk. There's Tysabri, which has an ongoing litigation related to that 

 product, Tysabri, and there's a biosimilar 

, which was FDA approved in August [2023].

The preliminary junction was denied in June, Sandoz has expressed a plan to launch at risk in the first half of 2024. This would be the first biosimilar launch for Tysabri which was approved almost 20 years ago so certainly something to keep an eye on there as well.

Intellectual property attorney, Ha Kung Wong, JD, discusses concerns about "bad patents" hindering biosimilar access, but assures that the FDA and United States Patent and Trademark Office are working to improve the system.

Biosimilars vs Bad Patents: Accessibility, Key Court Cases With Ha Kung Wong

The Top 5 Biosimilar Articles for the Week of March 4

Congress of European Crohn’s and Colitis Organisation (ECCO)

, Celltrion and Samsung Bioepis presented new finding from their respective biosimilar analyses, demonstrating positive safety and efficacy measures for the biosimilars as treatments for Crohn disease (CD) and ulcerative colitis (UC).

 announcement that it will investigate whether comparative efficacy tests should be needed for a biosimilar to receive regulatory approval.

 Samsung Bioepis provided multiple updates on its biosimilar projects, including a 

 for its aflibercept biosimilar candidate as well as regulatory news in the European Union and Republic of Korea.

 After receiving 3 complete response letters, Alvotech has officially received 

US approval for its adalimumab biosimilar

 (AVT02; Simlandi), making it the first approval for the company, the 10th biosimilar to reference Humira, and the third interchangeable adalimumab biosimilar.

 primarily serve to uphold inflated list prices, typically prompted by loss of exclusivity, aiming to safeguard market share and counter biosimilar competition, although forthcoming legislative changes targeting high drug costs could lessen their significance moving forward.

Here are the top 5 biosimilar articles for the week of March 4, 2024.


Elder Asian woman with eye care treatment | Image Credit: Chinnapong - stock.adobe.com

Patients with neovascular age-related macular degeneration (nAMD) demonstrated comparable efficacy, safety, immunogenicity, and pharmacokinetics (PK) between reference aflibercept (Eylea) and QL1207, an aflibercept biosimilar.

 was conducted across 35 centers in China. Patients were screened from August 2019 to January 2022, and randomized to receive either 2 mg reference aflibercept or QL1207 intravitreally every 4 weeks for the first 3 months followed by 2 mg every 8 weeks until week 48. The phase 3 trial included participants 50 years or older who were blind to allocation along with assessors.

Out of 533 patients screened, a total of 366 were enrolled and assigned (reference group, n = 181; QL1207 group, n = 185). All 366 patients with nAMD were included in the full analysis set (FAS), while the per-protocol set (PPS) had 319 patients (aflibercept, n = 159; QL1207, n = 160). The FAS included patients who received at least 1 dose of the study drug and 1 efficacy assessment, and the PPS included patients in the FAS without any major protocol violations. The final analysis contained data on 321 patients, with 155 receiving reference aflibercept and 166 in the QL1207 group.

Results found the reference aflibercept group had an average (SD) age of 67.1 (8) years while QL1207 had an average of 67.4 (8.9) years. The average best-corrected visual acuity (BCVA) was 56.1 (11.7) letters vs 56.3 (11.8) letters, with 80% and 80.7% patients having a score of 45 letters or more. The mean central retinal thickness area was 428.2 (178.1) mm vs 463.5 (193.3) mm while average choroidal neovascularization (CNV) leakage areas were 3.99 (4.14) vs 3.99 (4.13) mm

On average, the BCVA changes in the FAS from baseline at week 12 were 11 (9.2) letters in the reference aflibercept group and 10.2 (8.8) letters in the QL1207 group. The least-squares mean (LSM) changes in BCVA were 10.4 letters vs 11.5 letters from baseline to week 12 with a difference of –1.1 letters. No significant differences were found among the primary endpoints in either group. Patients with a BCVA score greater than or equal to 45 letters had a –1 LSM difference while patients with less than 45 letters had a difference of –1.6 LSM at baseline. At week 12, the LSM remained within the equivalence margin.

From baseline to week 52, LSM changes were –183 mm vs –208.4 mm, with a 25.4 mm difference in LSM. At week 52, LSM changes in CNV leakage area were –2.72 vs –2.61 LSM with a corresponding difference of –0.11 mm

. Similarities at other timepoints were similar in the 2 groups as well.

Safety among the reference aflibercept and QL1207 groups had comparable incidences of treatment-emergent adverse events (TEAE; 71.8% vs 71.4%, respectively). Similar ocular (29.8% vs 28.1%), fellow eyes (13.8% vs 19.5%), and non-ocular TEAEs (56.9% vs 60%) were reported in the reference aflibercept and QL1207 groups, respectively. Intraocular pressure increased (13.3% vs 11.9%), conjunctival hemorrhage (6.1% vs 5.9%), eye pain (1.7% vs 2.7%), ocular hypertension (1.1% vs 2.2%), cataract (1.7% vs. 1.6%), and conjunctivitis (1.7% vs. 1.6%) were the most common TEAEs among the aflibercept and QL1207 groups, respectively. Neither group had TEAEs leading to death, but 4 patients in the reference aflibercept group and 2 patients in the QL1207 group discontinued treatment due to related TEAEs.

The immunogenicity and PK analysis included 365 patients with similar incidences of positive antidrug antibodies (ADAs) between reference aflibercept and QL1207 (7.7% vs 7.1%). Both groups had comparable plasma drug concentrations and PK parameters as well as similar vascular endothelial growth factor levels as well.

The study was limited to only Chinese patients which arises caution when considering these results for other ethnicities. The optical coherence tomography angiography was not implemented for the CNV assessment due to its lack of validation during study design in the clinical trial setting.

Authors concluded with their supported evidence of QL1207 as an alternative option to the originator when treating patients with nAMD in China.

Li B, Fan K, Zhang T, et al. Efficacy and safety of biosimilar QL1207 vs. the reference aflibercept for patients with neovascular age-related macular degeneration: A randomized phase 3 trial. 

2024;(13):353-366. doi:10.1007/s40123-023-00836-4

A Chinese phase 3 trial found biosimilar QL1207 to be as effective and safe as reference aflibercept (Eylea) for the treatment of neovascular age-related macular degeneration (nAMD).