Hyrimoz

Product Profile:

Adalimumab-adaz (Hyrimoz)

Drug Category: anti-TNF inhibitor/autoimmune

Target Indications: Treatment of ankylosing spondylitis, Crohn’s disease in adults, plaque psoriasis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis

Manufactured by Sandoz; will be marketed by Sandoz

Summary: Hyrimoz is an FDA-approved biosimilar version of adalimumab (reference product, Humira®, AbbVie).

Originally known as GP2017, Sandoz submitted a biologic license application for approval via the 351(k) biosimilar pathway in January 16, 2018. The Food and Drug Administration (FDA) approved the biosimilar in October 31, 2018 (without convening its Advisory Committee). The European Medicines Agency approved Hyrimoz for use in the EU on July 26, 2018.

Though approved, it is not yet marketed in the US  Like several other manufacturers of approved biosimilar versions of adalimumab, Sandoz has signed a licensing agreement with AbbVie that would enable launch in September 2023.

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.  Besides Hyrimoz, Sandoz has obtained FDA approvals for Zarxio (filgrastim-sndz) and Erelzi (etanercept-szzs). Its biosimilar version of pegfilgrastim is awaiting FDA approval (though approved in the EU). Sandoz has withdrawn its biosimilar rituximab from consideration for FDA approval (though also approved in the EU).  The company also markets a biosimilar infliximab in the EU.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Hyrimoz was the third adalimumab biosimilar to be approved by the FDA. It, like its competitors, is not yet available on the US market.

ADALIMUMAB BIOSIMILARS APPROVED BY THE FDA: FDA FILING DATES AND ACTIONS

Biosimilar

Manufacturer

Brand Name & Designation

Innovator Product

FDA Filing Date

Status

Adalimumab

Amgen

Amjevita (adalimumab-atto)

Humira

November 25, 2015

Approved September 23, 2016, all indications; not yet marketed; Signed licensing agreement with AbbVie to launch January 2023

Adalimumab

Boehringer Ingelheim

Cyltezo (adalimumab-adbm) 

Humira

January 18, 2017

Approved August 29, 2017; not yet marketed

Adalimumab

Sandoz

Hyrimoz (adalimumab-adaz)

Humira

January 16, 2018

Approved October 31, 2018; Signed licensing agreement with AbbVie to launch Sept 2023

ADALIMUMAB BIOSIMILARS IN DEVELOPMENT

Company Name, Country

Product Name

Stage of Development

Samsung Bioepis/Merck

SB5

Filed for FDA approval September 27, 2018; decision expected Q2 2019; Signed licensing agreement to launch in June 2023

Mylan/Fujifilm Kyowa Kirin Biologics

FKB327

Signed licensing agreement with AbbVie to launch August 2023

Coherus Biosciences

CHS-1420

Completed phase 3 study; FDA submission anticipated Q4 2019

Pfizer

PF-06410293

Completed phase 3 study; Signed licensing agreement with AbbVie to launch November 2023

Momenta

M923

Completed phase 3 study; FDA filing in 2019; signed licensing agreement with AbbVie to launch in Dec 2023

Fresenius Kabi

MSB11022

Completed phase 3 study

Celltrion

CT-P17

Phase 3 trials to be completed in 2020

See article below on latest updates on licensing agreements with Abbvie.

Update: Who Has Signed Abbvie Licensing Agreements for Adalimumab Biosimilars?

(January 28, 2019) At least 8 biosimilar manufacturers have signed licensing agreements with Abbvie, which allow immediate European launches for approved adalimumab biosimilars and sequentially timed US launches in 2023. This database displays the manufacturer, product name, and date of anticipated launch. Note: not all of these biosimilar adalimumab are approved in the US.

More Adalimumab News: Abbvie Signs a Licensing Deal With Coherus, Coherus Sues Amgen for Patent Infringement

(January 28, 2019) Coherus becomes the eighth biosimilar maker to sign a licensing agreement with Abbvie, and it also becomes the first biosimilar maker to sue another (Amgen) for patent infringement.

Pfizer Pulls One Biosimilar Adalimumab Application From the EMA

(December 17, 2018) Earlier this month, Pfizer notified the European Medicines Agency (EMA) that it was withdrawing one of its two applications for approval of its biosimilar adalimumab.

Boehringer Ingelheim Decides to Market Cyltezo® in the US Only

(November 28, 2018)  Boehringer has now announced its intention to discontinue all efforts to market and develop any biosimilars outside of the US market.

Pfizer Signs Licensing Deal With Abbvie on Adalimumab Biosimilar Candidate

(November 27, 2018)  According to the announcement, Pfizer will market this agent (PF-06410293), if approved by the Food and Drug Administration, in November 2023.

A Third Biosimilar Adalimumab Approval in the US

(November 1, 2018)  The Food and Drug Administration (FDA) announced yesterday the approval of adalimumab-adaz from Sandoz. The new agent, dubbed Hyrimoz™, will not be launched in the US until 2023.

Word From the Adalimumab Front: A Conversation With Molly Burich, MS, Boehringer Ingelheim: Part 2

(October 24, 2018) In part two and the conclusion of this interview, Molly Burich, MS, Director, Public Policy: Biosimilars and Pipeline, speaks to Boehringer Ingelheim’s progress in Cytelzo interchangeability studies, its plans for the product in Europe in the face of several adalimumab biosimilars launches in the EU, and also the complexity inherent in CMS’s plans to move biologic agents from part B to part D coverage.

Word From the Adalimumab Front: A Conversation With Molly Burich, MS, Boehringer Ingelheim: Part 1

(October 23, 2018)  In the first portion of a two-part interview with Molly Burich, MS, Director, Public Policy: Biosimilars and Pipeline, Boehringer Ingelheim, we cover the challenges of driving biosimilar uptake, as well as the unique situation that has focused this manufacturer’s attention on biosimilars and interchangeability.

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.

Up to 5 Biosimilar Horses in the Race for Adalimumab in Europe: Heading for the Starting Gate

(August 3, 2018) A long-sought dream in the United States will be a welcome reality in Europe this October: a stampede for Abbvie’s marketshare with adalimumab biosimilars and the savings that go with it.

An FDA Filing for Momenta’s Adalimumab Biosimilar Coming Soon?

(June 22, 2018) In its recent investor conference, the company disclosed that it is ready to send M923, its adalimumab biosimilar, to the agency for approval.

With the Samsung Bioepis Deal, Abbvie Tightening Its Grip on the US Adalimumab Market

(April 6, 2018) Samsung Bioepis and Biogen has reached a deal with Abbvie that would enable it to market its biosimilar adalimumab (should it be granted approval) in June 2023.

What Will Cost Savings on 2023 Adalimumab Biosimilars Really Be Worth?

(February 5, 2018) AbbVie executives are sticking to their pledge to restrict annual price increases on Humira® below 10%, but even payer price protections won’t mitigate the increasing expenditures before adalimumab biosimilars hit the market.

Sandoz Files 351(k) Application for Adalimumab Biosimilar

(January 16, 2019) Sandoz announced that it has thrown its hat in the ring for another Humira biosimilar.

Are We Now Thinking “Authorized Biosimilars”?

(October 3, 2017) Authorized generics have been around for a couple of decades. They can be a challenge to payers, health systems, and patients who are seeking the price-reduction benefits borne out of normal competition. The Amgen-Abbvie agreement for the former’s adalimumab biosimilar is right out of this playbook.

FDA Approves New Humira Biosimilar, Bypasses Advisory Board Route

(August 29, 2017) Boehringer Ingelheim Pharmaceuticals, Inc. announced August 29 that it had received approval from the Food and Drug Administration (FDA) for its first biosimilar.

Boehringer May Seek Interchangeable Designation for Adalimumab Biosimilar

(July 28, 2017)  One biosimilar developer announced on July 27 that it is embarking on a study specifically to prove interchangeability of its biosimilar version of adalimumab.

Impressions on the Adalimumab Biosimilar Arthritis Advisory Committee Meeting

(July 12, 2017) FDA Advisory Committee members considered the data package provided by Amgen to be comprehensive, but the 26-0 vote was not without some interesting points and drama.

The Benefits of Biosimilars

The Promise of Biosimilars

Clinical Trials of Hyrimoz

Rheumatoid Arthritis

A Randomized, Double-blind, Parallel-group, Multicenter Study to Demonstrate Similar Efficacy and to Compare Safety and Immunogenicity of GP2017 and Humira® in Patients With Moderate to Severe Active Rheumatoid Arthritis

In this study, 353 patients were randomized and assigned to one of two study groups: treatment with GP2017 for up to 48 weeks, or treatment with the reference drug (Humira) for 24 weeks, and then switched to GP2017 through week 46. To be eligible in group 2 for the switch to GP2017, patients must have received at least a moderate response on the DAS28-CRP score. Study period 1 was defined as weeks 1–24 and study period 2 was defined as weeks 25–48. Drugs were administered in 40 mg doses, subcutaneously from prefilled syringes. A total of 163 patients in group 1 and 168 in group 2 completed the first study period. A total of 145 individuals in group 1 completed study period 2, along with 158 in the group. Of note, in the second study period, 5 in group 1 withdrew from the investigation because of adverse events compared with none in group 2.

The Table below describes the efficacy results for study period 1:

Variable

Group 1 (GP2017)

Group 2 (Humira)

EULAR Remission (wk 12)

25.4%

27.5%

EULAR Remission (wk 24)

38.6%

51.4%

EULAR Good Response (wk 12)

40.5%

45.7%

EULAR Good Response (wk 24)

60.3%

67.4%

ACR20 (wk 24)

87.4%

94.2%

ACR50 (wk 24)

61.4%

71.0%

ACR70 (wk 24)

37.8%

38.4%

The Table below describes the efficacy results for study period 2:

Variable

Group 1 (GP2017)

Group 2 (Humira)

At week 48

ACR20

86.1%

88.1%

ACR50

66.7%

64.3%

ACR70

45.4%

43.7%

Although there were some numerical differences between the groups, none reached the level of statistical significance, and met the prespecified criteria for biosimilarity.

The investigators found that the safety profiles between the biosimilar and reference treatments, and after the switches to be acceptable. Therefore, they concluded that GP2017 resulted in similar outcomes to the reference agent.

 

Psoriasis

Phase III Randomized Study of the Proposed Adalimumab Biosimilar GP2017 in Psoriasis: Impact of Multiple Switches

In this double-blinded, phase 3 trial, researchers from multiple centers tested GP2017 against the reference agent Humira in 465 adult patients with moderate-to-severe symptoms of plaque psoriasis. In addition, the investigators sought to determine the clinical effect and safety of multiple switches among the biosimilar and reference products.

Over the course of 51 weeks, patients were given either agent 80 mg subcutaneously at baseline, followed by 40-mg biweekly doses from week 1 through week 16. After this time, all patients continuing in the study were randomized to either maintain their current therapy or switch to the alternative treatment for weeks 17 through 35. For the final phase of the study (wk 36-51), patients were randomized once again to either maintain their current treatment or be switched back to their original therapies. The study’s primary end point was the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 16. The secondary end points included was change in PASI over time, percentage of those achieving PASI 90 and 100, and safety and immunogenicity targets through the latter switched study period.

Of the initial 231 patients in the biosimilar group and 234 in the US-licensed Humira group, 201 completed the initial phase. Sixty-three patients were switched from biosimilar to Humira in period 2, as were 63 who switched from Humira to the biosimilar. During the final period, 52 switched from biosimilar to reference product, and 56 switched from reference product to biosimilar.

The PASI improvement scores (per-protocol groups) are given in the Table below:

Variable

GP2017 Group

Humira Group

At week 17

PASI 75

71.4%

68.6%

PASI 90

51.6%

44.8%

PASI 100

21.9%

16.5%

At week 35

Switched to Humira

Switched to GP2017

PASI 75

70.6%

73.5%

PASI 90

62.7%

53.1%

PASI 100

35.3%

28.6%

At week 51

Switched Back to GP2017

Switched Back to Humira

PASI 75

75.0%

76.7%

PASI 90

60.4%

48.8%

PASI 100

31.3%

25.6%

These figures did not differ significantly from those patients who continued therapy with either GP2017 throughout the study or Humira throughout the study.

The researchers did not uncover any clinically significant differences in terms of safety or immunogenicity between the individual study groups (who switched or continued therapies). The percentages of patients who exhibited antidrug antibodies during the initial period were 34.1% taking the reference agent and 36.8% assigned to the biosimilar. During treatment period 2, antidrug antibodies were detected in 45.1% who continued with the reference agent and in 39% who switched to the biosimilar (vs. 35.8% who continued with the biosimilar and 47% who switched to the reference product).

Based on these results, the researchers concluded that the differences between GP2017 and US-licensed Humira were minor, and switching between the products had no meaningful effect on the treatment efficacy, safety, or the development of antidrug antibodies.

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