Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

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

Articles

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).

QL1207 Biosimilar Shows Equivalent Efficacy, Safety to Aflibercept in Treating nAMD

The Top 5 Biosimilar Articles for the Week of February 26

The Revolution that Died on its Way to Dinner Table,

” reported in the New York Times on February 9, summed up the history of the gleaming vision of a world just beyond the present: a world in which a high-tech factory housing bioreactors will produce formed steaks, millions of pounds a day to feed the world at an affordable cost—

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

, Celltrion and Samsung Bioepis presented new finding from their respective biosimilar analyses, demonstrating 

Crohn disease (CD) and ulcerative colitis (UC)

 (VA) has chosen to replace Humira (adalimumab) with Organon’s biosimilar version on its national formulary; Biocon Biologics and Sandoz announce a new partnership in Australia for 2 biosimilars; Alvotech settles with Johnson & Johnson over its biosimilar to Stelara (ustekinumab) for the European and Canadian markets.

 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.

After receiving several complete response letters (CRLs), Alvotech has officially received 

FDA approval for its adalimumab biosimilar

 (AVT02; Simlandi), making it the first US approval for the company and tenth biosimilar referencing Humira (adalimumab). The product was also approved as an interchangeable biosimilar.

To read all of these articles and more, visit 

Videos

Here are the top 5 articles for the week of February 26, 2024.

Ha Kung Wong, JD 2

, brings a wealth of experience to the field of intellectual property law, specializing in patent and trade secret litigation. Beyond courtroom battles, his expertise extends to negotiating complex agreements for mergers, acquisitions, and collaborations across diverse industries, including pharmaceuticals, biologics, and cutting-edge fields like digital health and artificial intelligence. Wong's client roster boasts renowned names like Alkermes, Allergan, and the Bill & Melinda Gates Foundation.

 delved into Wong's insights in an interview on proposed patent law changes poised to significantly impact the biosimilars sector. These changes encompass limitations on asserted patents, the potential elimination of interchangeability requirements, and increased scrutiny of pharmacy benefit managers (PBMs).

Do you foresee any potential shifts or reforms in patent law that could positively or negatively impact the biosimilars sector in the near future?

Predicting whether there will be statutory shifts or reform in patent law is like trying to predict what will happen in the next 

 movie—you have no idea what specifically is going to happen but it's probably going to have some explosions that ultimately, will not be applicable to the real world. That being said, there are a few things I think that we might want to keep an eye on. I say "very few" only because we've seen a lot of things introduced and not a lot of follow through. There's a lot of good intentions out there, but there's not a lot of follow through. That being said, here it is.

First of all, Senators [Peter] Welch [D, Vermont], [Mike] Braun [R, Indiana], and [Amy] Klobuchar [D, Minnesota] introduced legislation in the Senate, and Representative [Jodey] Arrington [R, Texas] in the House on January 2024 that would limit the number of patents that could be asserted in a patent litigation. If this were to proceed, this may or may not have a practical effect because we've seen that most Bundled Payments for Care Improvement 

lawsuits that have been asserted are asserted on 10 or less patents. So, having an artificial limit may not make it any better. But it might. Who knows? It is certainly something to keep an eye on.

The Biosimilar Red Tape Elimination Act was introduced in July 2023 by Senators [Mike] Lee [R, Utah], [Ben Ray] Lujân [D, New Mexico], Braun, and [J.D.] Vance [R, Ohio]. That bill would eliminate the 2 separate designations of biosimilars and interchangables, which we know, exist in the US and we are the only country that does that. Every other country in the world only has 1 level of biosimilarity. It's possible if the interchangability requirement was removed, there could be greater uptake of biosimilars due to the possibility of automatic substitution at the pharmacy level, like we see with generic drugs. There may be increased confidence in biosimilars because they would be seen as perhaps closer to the reference product.

The problem is that when people hear there's a "biosimilar" but there's a higher level called "interchangable", their automatic reaction is, "Well that means biosimilars are garbage, why would I want that? I want an interchangeable. Oh, there's no interchangable? Then I don't want that product."

I think it will help with consumer confidence, patient confidence, and will help with health care provider confidence because a lot of doctors just don't know the difference. 

In June 2023, Senators [Thom] Tillis [R, North Carolina] and [Chris] Coons [D, Delaware] reintroduced the Patent Eligibility and Restoration Act of 2023 to reform patentability requirements under Section 101. There, the bill seeks to clarify which inventions are eligible for patenting in the US. If that bill were to be passed, it would overturn Supreme Court decisions in Mayo, Alice, and Myriad, which we've all been talking about for 10 years. It would be really interesting to see how that would impact the pharmaceutical and biologics industry in particular.

Finally, there's been this increased congressional scrutiny of pharmacy benefit managers or PBMs. Congress has launched various investigations into PBM practices and while this isn't directly related to patent law reform, it could have a significant impact on biosimilar uptake given the preferential formulary coverage of biosimilars and how that plays a big role in whether biosimilars are used and whether cost savings are realized or not.

I've been on record saying this for a long time now. PBMs are middlemen that don't need to really be there, but at the end of the day, they end up increasing the cost for patients and it would be interesting to see if all this congressional scrutiny will lead to better cost savings for patients.

Ha Kung Wong, JD, examines proposed patent law changes that could significantly impact the biosimilars sector, including limitations on asserted patents, elimination of interchangeability requirements, and heightened oversight of pharmacy benefit managers.



Patent Shift Predictions, Legal Landscapes of Biosimilars With Ha Kung Wong

The Top 5 Biosimilar Articles for the Week of February 19, 2024.

 In its market sustainability for infused 

, IQVIA echoed the need to address issues regarding misaligned incentives regarding rebates, slow or limited uptake, and concerns about market viability, which will be crucial for ensuring the long-term sustainability of biosimilars and maximizing their benefits for the health care system.

 After a patient with multiple sclerosis (MS) was forced to pay exorbitant out-of-pocket costs for a brand name medication when she could’ve gotten a generic for way less, the patient filed a class action complaint against her employer, Johnson & Johnson (J&J), for violating the 

 that 3 of its oncology biosimilar products have won tender contracts in France and Italy, and an experimental oral delivery device utilizing an ustekinumab biosimilar was successful in a phase 1 study.

efficacy, safety, pharmacokinetics, and immunogenicity

 were found when comparing Stelara, originator ustekinumab, and CT-P43, an ustekinumab biosimilar candidate, in patients with moderate to severe plaque psoriasis.

 assessing several disease states found no significant differences in serious adverse events, deaths, or treatment discontinuations between patients who switched from reference products to biosimilars and those who did not.

Here are the top 5 biosimilar articles for the week of February 19, 2024.

The Top 5 Biosimilar Articles for the Week of February 19

Doctor holds stethoscope surrounding rituximab text | Image Credit: MQ-Illustrations - stock.adobe.com

A phase 3, randomized, double-blind study

 conducted in China found bioequivalence between reference rituximab (Rituxna) and HanliKang (HLX01), a rituximab biosimilar, in the overall survival (OS) and progression-free survival (PFS) in patients with diffuse large B-cell lymphoma (DLBCL).

Rituximab is a monoclonal antibody used to treat DLBCL as well as other aggressive cancers. HanliKang (HLX01) was developed in line with the China National Medical Products Administration (NMPA) and the World Health Organization. On February 22, 2019, China NMPA approved HLX01 as the first biosimilar in their country.

China’s standard care in the first line setting for patients with DLBCL is the combination of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The researchers randomized patients to receive either R-CHOP intravenously or HLX01 combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) as doses of 375 mg/m

Data from 27 hospitals across China was used to enroll 316 patients in the study, with the researchers using April 28, 2022, as a cut-off date (R-CHOP: n = 159; H-CHOP: n = 157). The 6 planned treatment cycles were completed by 91.8% of the R-CHOP while 87.3% patients made up the H-CHOP group. The median age of patients was 56.1 years old with the median duration of follow-up as 65.1 months. OS and PFS values were recorded at the 1-year, 3-year, and 5-year marks.

The International Prognostic Index (IPI) had 96.5% of patients in IPI 1 and 2, 47.2% had clinical stage III/IV disease, and 17.7% had bone marrow involvement. The study found no significant differences in efficacy or OS between either treatment groups. The 5-year OS rates were 75.4% and 81%, for R-CHOP and H-CHOP, respectively. For patients completing all 6 cycles, the 5-year OS rates were 77.6% and 83.3%, respectively. A similar number of patients died in both groups (R-CHOP, n = 41; H-CHOP, n = 31).

There were no statistically significant differences of PFS between the R-CHOP and H-CHOP treatment groups 5 years after completing all 6 cycles (PFS, 75.6% vs 79.6%).

For patients with low-risk DLBCL (IPI score 1 or 2), both R-CHOP and H-CHOP had similar 5-year OS rates (IPI 1: 80.2% vs 86.8%; IPI 2:68% vs 76.2%) and PFS rates (IPI 1: 75.3% vs 84.1%; IPI 2:68.2% vs 72%).

Patients with an IPI score of 1 had better outcomes than those with a score of 2 (OS: 83.1% vs 72.3%; PFS: 79.3% vs 70.2%). No significant differences were observed in OS or PFS between clinical stages I/II and III/IV (OS: 79.4% vs 76%; PFS: 79% vs 70.4%).

Limitations of the study included the likeliness of nonresponse bias with telephone follow-up and the absence of visual cues that compromise the data representation.

Study results were comparable with previous long-term follow-up studies administering rituximab in combination with chemotherapy in patients with DLBCL. Authors concluded, “HLX01 is an appropriate substitute for rituximab that can provide comparable efficacy in patients with low or low-intermediate IPI risk DLBCL.”

Qin Y, Song Y, Wang D, et al. Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study. 

. 2024;24(1):124. doi:10.1186/s12885-024-11876-9

A large Chinese study found that HanliKang (HLX01), a biosimilar rituximab, had similar overall survival and progression-free survival rates to the reference product (Rituxan) in patients with diffuse large B-cell lymphoma (DLBCL).

Biosimilar HLX01 Demonstrates Bioequivalence With Rituxan in DLBCL

The Top 5 Biosimilar Articles for the Week of February 12

 is just as effective as the originator drug (Enbrel) in treating Australian patients with rheumatoid arthritis (RA), leading to significant cost savings.

 showcased the success of biosimilars while also emphasizing the impact of inflation on different drug classes, particularly in oncology and immunology.

Since January 31, 2023, the United States has seen a boom in the adalimumab market. With 

 launching throughout the year, the US rheumatology, immunology, dermatology, and gastroenterology treatment spaces have a wealth of newer and cheaper alternatives to Humira (reference adalimumab).

In his latest column, Sarfaraz K. Niazi, PhD, highlights challenges in biosimilar development, emphasizing the 

 (USP) and advocating for collaboration and standardized guidelines to expedite cost-effective development without compromising safety or efficacy.

Here are the top 5 biosimilar articles for the week of February 12, 2024. 

Dermatologist examining skin | Image Credit: fusssergei - stock.adobe.com

 found comparable efficacy, safety, pharmacokinetics (PKs), and immunogenicity between Stelara, the ustekinumab originator, and the biosimilar candidate, CT-P43 for patients with moderate to severe plaque psoriasis.

Patients varied among 34 different centers across Estonia, Poland, Ukraine, and the Republic of Korea to participate in 2 treatment periods ranging from January 2021 to November 2021. Treatment period I randomized patients to receive either the originator ustekinumab or CT-P43 from baseline to week 16. Treatment period II rerandomized patients to either continue receiving the originator, continue CT-P43, or switch from the originator to CT-P43 from week 16 to week 40. Eligible patients were 18 to 80 years old with more male patients than female in both the originator (male, n = 173, F: 80) and CT-P43 (M: 161, F: 95).

A total of 509 patients participated in treatment period I with 253 receiving the originator and 256 receiving CT-P43. Drug administration took place at week 0 and week 4 where patients less than or about 100 kg received 45 mg doses while patients more than 100 kg received 90 mg doses.

Treatment period II randomized patients to continue the originator, switch to CT-P43, or continue CT-P43 from week 16 to week 40 (n = 125, 124, 253, respectively). Drug administration took place at weeks 16, 28, and 40 with doses adjusted at week 16 pre-dose to reflect any weight changes. Near the end of the study, 3 patients discontinued CT-P43 in the continued group (n = 250) and 2 patients discontinued treatment in the originator group (n = 123) while the switched group did not have discontinuations.

Efficacy results were comparable among treatment periods in improved Psoriasis Area and Severity Index (PASI) scores. At baseline, the average PASI score was 21.51 in the CT-P43 group and 20.88 in the ustekinumab group. At week 12, the proportions of patients who achieved PASI scores of 50/75/90/100% were 86.05 for CT-P43 and 83.99 for ustekinumab. By week 28, the proportions of patients who experienced improvements in their PASI scores were 92.55% in the continued ustekinumab group, 95.07% in the continued CT-P43 group, and 92.86% in the switched groups.

Efficacy endpoints included patients’ Dermatology Life Quality Index (DLQI) score with patients in the CT-P43 group (DLQI, 13.2) and the originator group (DLQI, 11.9) at baseline. By week 12, the mean changes from baseline in DLQI score were –9.7 and –8.5 for CT-P43 and the originator groups, respectively. At week 28, the continued CT-P43 group, continued originator group, and the switched to CT-P43 group had mean DLQI score changes of –10.9, –8.8, and –9.4, respectively.

Safety was evaluated based on treatment-emergent adverse events (TEAEs) where 18 patients in CT-P43 and 15 in the originator groups experienced at least 1, none leading to discontinuation. Treatment-emergent serious adverse events (TESAE) were present in 4 patients in each group. The continued CT-P43 group, continued originator, and switched to CT-P43 group had 4, 5, and 6 patients, respectively, with a drug experience related to TEAE but no TESAEs. The majority of TEAEs were grade 1-2 in intensity. Baseline injection-site reactions (ISRs) 3 patients in the biosimilar group and 2 in the originator group, but 0 patients in the continued groups experienced them. Those who switched to CT-P43 had an ISR in 2 patients.

Three patients discontinued the study drug in the biosimilar group and 4 discontinued in the originator ustekinumab group.

PKs were consistent with serum ustekinumab concentrations at all timepoints measured. Treatment groups and dose were generally similar, including after transitioning from originator to biosimilar candidate or vice versa.

Regarding immunogenicity, patients in the CT-P43 group had lower results of positive antidrug antibodies (ADAs) compared with the originator in treatment period I. No major change in ADA frequency occurred in period II. By week 28, ADA positive patients included 26 in the CT-P43 group, 21 in the continued reference product group, and 22 who switched to CT-P43. Treatment period I had slightly lower ADA-positive serum concentrations vs ADA-negative subgroups among both treatment II groups. There were no correlations in treatment period I between ADA positivity and TEAEs, TESAEs, ISRs, or hypersensitivity reactions.

Limitations included singular focus on the switch rather than the absence of multiple switch combinations throughout the study design. Patients and other investigators remained blinded but staff administering drugs could not be blinded. The study also took place during the COVID-19 pandemic and excluded patients with protocol deviations.

Papp KA, Lebwohl MG, Thaçi D, et al. Efficacy and safety of candidate biosimilar CT-P43 versus originator ustekinumab in moderate to severe plaque psoriasis: 28-week results of a randomised, active-controlled, double-blind, phase III study. 

. 2024;38(1):121-131. doi:10.1007/s40259-023-00630-5

Similar efficacy, safety, pharmacokinetics, and immunogenicity were found when comparing Stelara, originator ustekinumab, and CT-P43, an ustekinumab biosimilar candidate, in patients with moderate to severe plaque psoriasis.

Biosimilar Candidate CT-P43 Shows Biosimilarity With Ustekinumab Originator in Plaque Psoriasis

Ha Kung Wong, JD 1

, Ha Kung Wong, JD, is a lawyer practicing general intellectual property law, emphasizing patent and trade secret litigations. Wong negotiates for mergers, acquisitions, vendor agreements, and collaborations in pharmaceuticals, biologics, chemistry, medical devices, digital health, and artificial intelligence. He has represented Alkermes, Allergan, Alnylam, Materia, Shionogi, Stemline, UCB, and Bill & Melinda Gates Foundation and Gates MRI as clients.

This interview for the Center for Biosimilars

 focuses on Wong's perspective of the patent legal system, the importance of this process, and how it affects biosimilar development.

Can you explain the patent legal system biosimilars are required to undergo and why this process is important to their development?

Sure, so for biosimilars, there's the BPCIA or the Biologics Price Competition and Innovation Act of 2009, which is actually an optional framework of information exchanges between biosimilars and the reference product sponsor, or what we call the RPS, prior to filing an infringement lawsuit.

The BPCIA allows for 2 phases of litigation. One, following the biosimilars aBLA [abbreviated biologics license application] submission and the second phase triggered by the biosimilars notice of commercial marketing. Now, the idea is that the most important patents can be dealt with while the biosimilar application is under FDA review. That gives the possibility of resolving the lawsuit after only litigating a small subset of patents, instead of the RPS' entire portfolio. That can be quite large and sometimes in the hundreds.

So, to start this first phase exchange of materials, which is often referred to as the patent dance, the biosimilar notifies the RPS that the FDA has accepted its biosimilar application within 20 days of that acceptance and provides the RPS with its aBLA and "other manufacturing information".

That starts off this kind of exchange of information regarding the patents that might be infringed by the biosimilar and which they think might be likely to be licensed whether the biosimilar feels like there is an infringement, validity, or enforceability problem or not. Ultimately, what happens in the first round of litigation is that you narrow the number of patents that you actually litigate right away. If the parties can't agree, the BPCIA gives a provision for determining the list of patents that can be litigated in the first phase and the remainder gets litigated in the second phase.

For most BPCIA litigations that most parties have participated in at least some part of the dance and as I mentioned before, it was after the statute came out it was decided by the courts that this was optional.

A lot of people said, "Well, why would anybody go through this?" It turns out, it helps both sides, right? The biosimilar gets that chance to narrow it down to the patents that are most important so they're not expending an enormous amount of resources litigating hundreds of patents, and the RPS gets a chance to really zone in on the patents that are most important to them and try to protect them first, then try to seek licenses on those that can be some sort of settlement. So 24 of the litigations that have occurred, have completed this entire patent dance, 19 participated in some portion of it and didn't finish, but only 9 didn't participate.

You can see that even though it's optional, a lot of parties find some benefit to going through this process. Now, the interesting thing about it is that when it came out, I thought this is the most half-baked process ever.

That's still true, but it's better than nothing is what I think is happening. Most of the BPCIA litigations are actually ending in settlements. Thirty-one of 46, or 67%, of terminated BPCIA litigations ended in settlement or stipulated voluntary dismissals.

Very few cases have gotten the verdict, which is actually part of what we want. I think this statistic that I'm raising is demonstrating that the primary benefit of the BPCIA process is being met. That was to resolve any patent related disputes early, prior to impact on the market, thus allowing both parties to direct resources appropriately to their respective products and avoid the need to address potential damages.

In many ways, this is similar to what the Hatch-Waxman process was meant to address for small molecules. So far, it appears to be working for biologics and biosimilars, and really helping in development on both sides.

In an interview with Ha Kung Wong, JD, he addresses the patent legal system biosimilars are required to undergo and how this helps resolve patent disputes early in the development process. 

Navigating the Biosimilar Patent Landscape With Ha Kung Wong

The top 5 biosimilar articles for the week of February 5, 2024. 

 found that the introduction of biosimilar drugs significantly increased access to biologic therapies and Janus kinase (JAK) inhibitors for patients with rheumatic musculoskeletal diseases (RMDs), while also reducing treatment costs.

 greater biosimilar adoption than the English average after it implemented a new policy that prioritizes best-value biologics, including biosimilars, for new-start patients and those already treated with originators.

 (Cimerli) to Sandoz; Celltrion has completed its biologics license application filing for its tocilizumab biosimilar (CT-P47); Alvotech shares positive pharmacokinetic results for its denosumab biosimilar candidate.

 tend to be the most common type of patent referenced in litigation regarding biosimilar development, other patents actually have a greater impact on delays for biosimilar market launches.

Since January 31, 2023, the United States has seen a 

. With 9 adalimumab biosimilars launching throughout the year, the US rheumatology, immunology, dermatology, and gastroenterology treatment spaces have a wealth of newer and cheaper alternatives to Humira (reference adalimumab).

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

The Top 5 Biosimilar Articles for the Week of February 5

Etanercept medical injection | Image Credit: luchschenF - stock.adobe.com

 found the persistence of treatment was similar between the etanercept originator (ETN; Enbrel) and the biosimilar SB4 (Brenzys) treatment groups for patients with rheumatoid arthritis (RA), while considering the potential cost-savings implications. 

 in Australia as the first ever biologic disease-modifying antirheumatic drug (bDMARDs) with tumor necrosis factor inhibitors (TNFis). This was a major achievement because RA drugs are often inaccessible for patient populations due to their expensive price, whereas a biosimilar option often offers a cheaper alternative. The Australian Therapeutic Goods Administration approved the first etanercept biosimilar in 

Due to costly medications, the Australian government implemented a reference pricing policy guaranteeing price reductions of new treatments with biosimilars. A base price is set using the Pharmaceutical Benefits Scheme, fixing the cost as the lowest-priced option listed. The government ensures their benefits from biosimilars by setting statutory price reductions and disclosures, allowing both the originator and biosimilar drugs to cheapen market costs. Overall, the Australian reimbursement system has encouraged clinicians to prescribe biosimilar treatments, but ultimately, they have their own discretion when choosing the brand.

The OPAL study included real-world data that was entered into a customized electronic medical record (Audit 4). Patient data were included if the patient had an RA diagnosis, were between 18 and 95 years old, and initiated treatment with originator or biosimilar etanercept as the first recorded bDMARD or targeted synthetic (ts)DMARD treatment with at least 3 months of follow-up. RA severity for the cohort ranged from moderate to severe.

A total of 1153 patients with RA were considered eligible, of whom 386 had at least 3 months of follow-up recorded. Propensity score (PS) matching was utilized to increase the similarity of the baseline demographic and clinical features of the patients in the originator and biosimilar treatment groups. In total, 350 were matched for analysis (ETN, n = 209; SB4, n = 141).

Most patients were older than 50 and women (ETN: ≥ 50 years, n = 100; female, n = 144; SB4: ≥ 50 years, n = 69; female, n = 98). Based on disease activity measures, slightly higher scores were presented in the originator group for the Physical Global Assessment, Patient Global Assessment, Disease Activity Score 28, Crohn Disease Activity Index, and Simplified Disease Index.

Efficacy was measured through treatment persistence among participants. The average duration of treatment from baseline to 50% of participants discontinuing therapy was 19.4 months for the originator and 22.4 for the biosimilar. Both groups had participants who experienced adverse reactions, leading 25 patients on the originator and 17 patients on the biosimilar to discontinue treatment. The most common adverse reactions were rashes and injection site reactions (ETN, 3; Biosimilar, 4; SB4, 6; Biosimilar, 2). There were no switches from the biosimilar to the originator recorded among the population.

Before releasing the biosimilar in 2017, etanercept was priced at approximately AU $1600 (USD $1068) for 50 mg/L 4 × 1 mL pen device. Once the biosimilar was listed, both the originator and biosimilar were about AU $960 (USD $641), experiencing a 40% decrease in price due to reference pricing policies. The country experienced an average of 6 million dollars in cost-savings following the introduction of the biosimilar.

Study limitations were the focus on patients who began etanercept as a first-line agent during the study period. Patients switching from the originator to the biosimilar were not examined within the study.

The study authors stated, “Our analysis complements other published real-world studies, which described sustained low disease activity after switching from originator to biosimilar, and similar rates of persistence and disease activity relative to historical originator control groups.”

Deakin CT, Littlejohn GO, Griffiths H, et al. Comparative effectiveness of etanercept originator and biosimilar for treating rheumatoid arthritis: implications for cost-savings. 

. Published online November 27, 2023. doi:10.1111/imj.16296

Etanercept biosimilar SB4 is just as effective as the originator drug (Enbrel) in treating Australian patients with rheumatoid arthritis (RA), leading to significant cost savings.