Product Profile: Erelzi

Product Profile:

Etanercept-szzs (Erelzi)

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

Target Indications: Rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, plaque psoriasis.

Manufactured and marketed by Sandoz

Summary: Erelzi (GP2015) is a biosimilar version of entanercept (reference product, Enbrel by Amgen) manufactured by Sandoz. 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 in August 2016. The biosimilar is currently not marketed in the US due to litigation surrounding 5 patents. Amgen has patent protection until 2029 unless the court determines that Amgen’s patents are not valid. There are reports that a ruling may come in early 2019. When litigation is resolved, Erelzi will be marketed by Sandoz.

About the Manufacturer

Sandoz, although established as a division of Novartis in 2003, has its origins as an active player in the pharmaceutical industry in 1886. It has a considerable portfolio of biosimilar products approved by the FDA and in various stages of filing. These include Erelzi (etanercept-szzs), pegfilgrastim, adalimumab (awaiting FDA approval), and rituximab. The latter two have been approved for use in Europe, as has Erelzi and Zarxio (under the brand name Zarzio), and a biosimilar form of epoetin alfa.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

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

Company name

Product name

Stage of development

Coherus BioSciences

CHS-0214

Positive phase III results reported in June 2016

Samsung Bioepis (Biogen/Samsung)/
Merck

South Korea/USA

Brenzys/Benepali (SB4)

Brenzys approved in South Korea in September 2015. Benepali approved in EU in January 2016. Brenzys approved in Australia in July 2016 and in Canada in August 2016]. Positive switching data reported in June 2017. In Phase III trials in the US

Lupin/Yoshida/Mylan,

India/Japan/US

YLB113

Global phase III trials in rheumatoid arthritis completed in February 2018. Submitted for approval in Japan in March 2018. Submitted for approval by EMA in May 2018.  Phase III studies ongoing in the US

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..

Erelzi (etanercept), by Sandoz, is now available for patients in Canada

(August 21, 2017)  Sandoz, a Novartis division and the pioneer and global leader in biosimilars, announced today that Erelzi™ (etanercept) is now available in Canada.

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.

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

Published Trial Results

Pivotal Trial for Approval: Rheumatoid Arthritis

A study comparing GP2015 to Enbrel in subjects with rheumatoid arthritis (EQUIRA)

A phase III randomized, double-blind study in patients with moderate-to-severe rheumatoid arthritis who had an inadequate response to methotrexate 10–25 mg/wk compared GP2015 and the EU-licensed version of Enbrel for 24 weeks. After 24 weeks, those patients with at least a moderate clinical response continued treatment (for up to 48 weeks).

Patients self-administered subcutaneously GP2015 or etanercept 50 mg/wk during the initial study period. Methotrexate (10–25 mg/wk) and folic acid (≥ 5 mg/wk) were used concomitantly during the study. The primary endpoint was the change after 24 weeks in DAS28-CRP (Disease Activity Score using C-reactive protein) from baseline.

Analysis of the data showed a least-squares means difference of –0.04, 95% CI: –0.24, 0.15), indicating the products were equivalent.

Other results at 24 weeks:

GP2015

N=170

EU-etanercept

N=156

CAS28-CRP (Mean Change)

-2.78

-2.81

ACR20 (% responders)

88.8%

93.6%

ACR50 (% responders)

63.9%

71.2%

ACR70 (% responders)

33.7%

42.9%

EULAR good response

48.8%

48.1%

EULAR moderate response

48.8%

49.4%

Treatment-emergent adverse events were similar between the two groups (43.5% for GP2015 vs. 49.5% for etanercept) as were the severe adverse events (0.5% vs. 3.2%, respectively). The etanercept group had more injection-site reactions than did the GP2015 group (17.9% vs 7.0%, respectively). None of the patients had significant levels of antidrug antibodies (ADAs) detected.

Results at 48 weeks:

Continued GP2015

N=148

Switched to GP2015

N=131

ACR20 (% responders)

89.1%

82.4%

ACR50 (% responders)

63.3%

65.6%

ACR70 (% responders)

36.7%

42.0%

EULAR good response

54.4%

51.9%

EULAR moderate response

41.5%

44.2%

At 48 weeks, there were more treatment-emergent adverse events in the patients who continued with GP2015 treatment than in the group switching to GP2015 (42.9% vs 38.0%, respectively) but there were fewer serious adverse events in the continued treatment group (2.3% vs. 2.4%, respectively). No patients had injection site reactions in the continued GP2015 group while 3.6% of the switched group did.

Pivotal Trial for Approval: Psoriasis

A study to demonstrate equivalent efficacy and to compare safety of biosimilar GP2015 and Enbrel in patients with chronic stable plaque psoriasis (EGALITY). Approval of GP2015 was based on efficacy results at week 12 of this study but included all adverse events noted through 52 weeks.

A phase III randomized double-blind trial with 531 patients with clinically stable chronic plaque-type psoriasis who had previously received treatment with phototherapy or other systemic psoriasis treatment received either GP2015 50 mg or EU-licensed Enbrel 50 mg twice weekly via the subcutaneous route for 12 weeks. If as of 12 weeks the participants had achieve ≥50% improvement in Psoriasis Area and Severity Index (PASI) score, they were re-randomized to either to continue the same treatment with a weekly dosing schedule or to switch therapies every 6 weeks with weekly dosing until week 30 and then continue with weekly dosing with that final therapy until week 52.

The primary outcome measure was the difference in PASI 75 response rates at week 12 between the two treatment groups. The PASI 75 response rate was 73.4% in the GP2015 group and 75.7% in the etanercept group (a difference of –2.3%, CI –9.85 to 5.30), demonstrating therapeutic equivalency.

Other results at week 12:

GP2015 N=239

EU-Entanercept N=241

Change from baseline PASI score (%)

–56.11% SE(1.0578)

–55.48% SE(1.0511)

PASI 50 Response Rate (%)

99.2%

97.9%

PASI 75 Response Rate (%)

73.4%

75.7%

PASI 90 Response Rate (%)

39.2%

34.1%

Adverse events reported reflected 52 weeks of treatment. Patients receiving GP2015 for 52 weeks had more treatment-emergent adverse events than the patients receiving etanercept (N=98 for both groups, 59.8% vs. 57.3%, respectively). For the patients starting with GP2015 and then initially switching to EU-etanercept there were more treatment-emergent adverse event than the group initially switching to GP2015 (N=61 vs. 57; 61% vs. 59%, respectively). Injection site reactions were seen more often in the etanercept group than the GP2015 group during the first 12 weeks (14.2% vs. 4.9%, respectively) and these groups that continued their initial drug at 52 weeks (15.8% vs 8.5%, respectively). During the first 12 weeks of the study five patients in the etanercept group had ADA levels detected during the first four weeks of the study that were then negative after that time frame. In the group switched to EU-etanercept but currently receiving GP2015 one patient had positive ADA results.

Important Links and Resources

Information About Biosimilars

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US Biosimilar Filings Status

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