Eticovo

Product Profile:

Etanercept-ykro (Eticovo)

Drug Category: Anti-inflammatory (anti-TNF, autoimmune)

Target Indications: Ankylosing spondylitis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, and rheumatoid arthritis

Manufactured by Samsung Bioepis.

Summary: Eticovo (SB4) is a biosimilar version of entanercept (reference product, Enbrel by Amgen) manufactured by Samsung Bioepis. A biologic license application for approval via the 351(k) biosimilar pathway was submitted to the Food and Drug Administration (FDA) in September 2015 with approval given April 25, 2019. The biosimilar is currently not marketed in the US due to patent litigation; Amgen believes its patents won’t expire until 2029. Eticovo was approved by the European Medicines Agency for launch in the EU January 2016 (marketed as Benepali) . Sales in 2018 in Europe were reported by Samsung to be $485 million.

About the Manufacturer

Based in Incheon, South Korea, Samsung Bioepis Co., Ltd. develops and produces biopharmaceutical and biosimilar products. Samsung Bioepis is a joint venture between Samsung BioLogics and Biogen. It was first incorporated in 2012 . In early 2013 Samsung Bioepsis and Merck entered into a business agreement to develop and commercialize biosimilars. Samsung Bioepis Co., Ltd. also entered into a strategic collaboration agreement with Takeda Pharmaceutical Company Limited in August 2017. Besides Eticovo, Samsung Bioepis is an active player in the biosimilar market, with three other products approved in the US—Renflexis (infliximab), Ontruzant (trastuzumab), and Lusduna (insulin glargine, a transitional biosimilar product)—and several in the pipeline for the US market, including adalimumab (a Humira biosimilar), bevacizumab (an Avastin biosimilar), ranibizumab (a Lucentis biosimilar), and eculizumab (a Soliris biosimilar).

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Eticovo is the second etanercept biosimilar to be approved by the FDA. The product has not yet entered the marketplace.

APPROVED BIOSIMILARS

Company name

Product name

Status

Sandoz

Erelzi (etanercept-szzs)

Approved August 31, 2016 for all of Enbrel’s indications; not yet marketed

BIOSIMILARS IN DEVELOPMENT

Company name

Product name

Stage of development

Coherus BioSciences

CHS-0214

Positive phase III results reported in June 2016, no longer mentioned in Coherus’ pipeline

Lupin/Yoshida/Mylan, India/Japan/US

YLB113

Global phase III trials in rheumatoid arthritis completed in February 2018. Approved in Japan in April 2019. Submitted for approval by EMA in May 2018.  US filing anticipated 2020

Celltrion, South Korea

CT-P05

No clinical trials underway; current status not disclosed

Sandoz Loses Patent Litigation Against Amgen's Enbrel

(August 9, 2019) A US District Court judge sided with Amgen in its patent case against Sandoz. This could mean that Amgen’s key Enbrel patents are protected until 2029.

Second Etanercept Biosimilar Receives FDA Approval

(May 2, 2019) Samsung Bioepis scored another biosimilar approval in the US, as the Food and Drug Administration gave its nod to etanercept-ykro on April 25, 2019. Formerly known as SB4, Samsung Bioepis dubbed this agent Eticovo™. It is the second  Enbrel® biosimilar to to receive US approval.

Part B to Part D and Other Questions: How CMS’s Plans Could Affect Biosimilars

(August 10, 2018)  Some of these tactics are a bit late to the party, as commercial insurers and health plans have been employing them for years. To the extent that an injectable treatment can be managed through the pharmacy benefit rather than the medical benefit, the drug can be easily subjected to prior authorization, step therapy, quantity limits, and other tools routinely used.

Let's not Knock Innovation, but Biosimilars Exist for the Sake of Competition

(June 29, 2018)  What is the real benefit of biosimilars? Does biosimilar development detract from efforts to produce innovative medicines? Is the main societal benefit biosimilar cost savings?

Analyzing FDA Chief Gottlieb's Remarks--Part 2: FDA and Marketing Exclusivity

(April 2, 2018)  Food and Drug Administration Chief Scott Gottlieb, MD, received a great deal of coverage for his recent remarks on providing better access to biosimilars. He seems intent on finding solutions to the underlying problems in delayed biosimilar launches..

Sandoz receives EU approval for Erelzi (biosimilar etanercept)

(June 30, 2017) The European Commission (EC) has approved Sandoz’ (a Novartisdivision) Erelzi (biosimilar etanercept) for use in Europe, to treat multiple inflammatory diseases. Erelzi is approved for use in all indications of the reference medicine, Enbrel.

Frustration Mounts as Sandoz’s Etanercept Biosimilar Launch Delayed

(January 27, 2017) Sandoz’s Erelzi™, which was approved by the Food and Drug Administration on August 30, 2016, has been caught in the patent litigation web. The originator drug, Amgen’s Enbrel® was first approved in 1998.

Samsung Bioepis' SB4 (BRENZYS™) Becomes First Etanercept Biosimilar to Receive Regulatory Approval in Canada

(September 12, 2016) Samsung Bioepis’ etanercept biosimilar SB4 approved for use in Canada for the treatment of rheumatoid arthritis and ankylosing spondylitis.

First New Enbrel Biosimilar Approved by FDA

(August 31, 2016) Sandoz received approval by the Food and Drug Administration to market its biosimilar version of Enbrel® on Tuesday, August 30th. The FDA is calling this agent etanercept-szzs. It is the first biosimilar for etanercept approved for use in the US.forts.

Etanercept Basics

TNF Alpha Inhibitors in Rheumatoid Arthritis

Clinical Trials of Renflexis

Phase 3 Trials

A phase III randomised, double-blind, parallel-group study comparing SB4 with etanercept reference product in patients with active rheumatoid arthritis despite methotrexate therapy

In a phase III randomized, double-blind, parallel-group investigation, 596 patients with moderate-to-severe rheumatoid arthritis who had an inadequate response to methotrexate therapy were given either a weekly dose of SB4 (299 patients) or Enbrel (sourced outside of the US) (297 patients). This study took place across 10 European, Asian, and Latin American countries. Percentage of patients attaining an ACR20 response after 24 weeks of therapy was the primary endpoint. ACR50 and ACR70 responses were also measured. Secondary endpoints included immunogenicity and safety outcomes.

A total of 283 and 268 completed 24 weeks of therapy with SB4 and Enbrel, respectively. The per-protocol results (481 patients) at 24 weeks are as follows:

SB4

N=283

Reference etanercept

N=268

ACR20 (% responders)

78.1%

80.3%

ACR50 (% responders)

46.6%

42.3%

ACR70 (% responders)

25.5%

22.6%

Mean improvement in DAS28 score

2.6

2.5

Achieving good EULAR response

32.1%

29.8%

Treatment-emergent adverse events

55.2%

58.2%

The incidence of serious treatment-emergent adverse events were similar between the two groups and 5.0% and 6.4% of patients in the SB4 and Enbrel groups, respectively, discontinued treatment. The researchers found that the SB4 was associated with a significant lower incidence of antidrug antibodies at 24 weeks (0.7% vs. 13.1%, respectively; P < .001).

On the basis of these results, the investigators concluded that the efficacy and safety measures associated with SB4 were not inferior to those of the reference etanercept product.

52-Week Extension Study. A 52-week extension study was performed, based on the same patient population. In this study, ACR20 response rates continued to be equivalent (80.8% in the SB4 group, 81.5% in the reference drug group). In this study, the investigators also evaluated radiographic evidence of progression of rheumatoid arthritis, finding that to be no significant differences between the biosimilar and reference drug. Antidrug antibody development remained lower in the SB4 group than the reference drug group (1.0% vs. 13.2%, respectively).

Long-term efficacy and safety in patients with rheumatoid arthritis continuing on SB4 or switching from reference etanercept to SB4.

As part of the open-label extension trial above, the authors analyzed outcomes of patients who were switched to receive the biosimilar agent from the reference product Enbrel. In this study, patients were randomized to switch or continue on therapy after 52 weeks and followed up for another 48 weeks.

Two hundred forty-five patients entered this phase of the extension trial, with 126 continuing to receive infusions of SB4, 119 who were originally taking Enbrel were switched to SB4, The results after the 48-week follow-up are shown below:

 

Continued on SB4

N=126

Switched from Enbrel to SB4

N=119

ACR20 (% responders)

77.9%

79.1%

ACR50 (% responders)

59.8%

60.9%

ACR70 (% responders)

42.6%

41.7%

EULAR good response

48.8%

54.8%

EULAR moderate response

44.6%

34.8%

Differences in safety through week 100 were not seen (but the investigators add that the study was not statistically powered to detected these differences in adverse events). One patient in the subset continuing on SB4 therapy died as a result of hepatic cancer, which was judged to be related to this treatment.  On the basis of these results, the researchers concluded that switching from the reference agent to SB4 does not result in negative outcomes.

Phase 1 Studies

Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of SB4 in Healthy Male Subjects

A Randomised, Open-label, Two-period, Two-sequence, Single-dose, Cross-over Study to Compare the Pharmacokinetics, Safety, and Tolerability of the Autoinjector and Pre-filled Syringe of SB4 in Healthy Male Subjects

Important Links and Resources

Information About Biosimilars

Additional Patient Assistance Information

US Biosimilar Filings Status

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