Hulio

Product Profile:

Adalimumab-fkjp (Hulio)

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

Will be manufactured by Fujifilm Kyowa Kirin Biologics and marketed by Mylan (Viatris)

Biosimilar Drug Profile: Hulio is an FDA-approved biosimilar version of adalimumab (reference product, Humira®, AbbVie).

Originally known as FKB327, Mylan, which is responsible for commercialization of Hulio, submitted a biologic license application for approval via the 351(k) biosimilar pathway in the third quarter of 2019 (the application date was not publicly announced). The Food and Drug Administration (FDA) approved the biosimilar on July 6, 2020. This agent was approved in the European Union in October 2018 and has launched there.

Though approved in the US, it is not yet marketed here. Like several other manufacturers of approved biosimilar versions of adalimumab, Mylan (now known as Viatris) and its partner Fujifilm Kyowa Kirin Biologics signed a licensing agreement with AbbVie; under the agreement, it will able to launch the drug in August 2023.

About the Manufacturer

Mylan and Fujifilm Kyowa Kirin Biologics initiated a manufacturing and marketing relationship in 2018 for this agent. Mylan (now Viatris) is headquartered in Pittsburgh, whereas Fujifilm Kyowa Kirin Biologics has its headquarters in Tokyo. Mylan has been an active player in the biosimilar field. It recently rebranded itself Viatris after acquiring Pfizer’s Upjohn subsidiary. Mylan also has partnerships with Biocon for several biosimilar products, including approved bevacizumab and pegfilgrastim biosimilars, an insulin follow-on product, and several investigational biosimilars. Fujifilm launched its Kyowa Kirin Biologics subsidiary in 2012, and it is also working on a biosimilar version of bevacizumab, which it will develop and commercialize through Centus Biopharmaceuticals (a joint venture with AstraZeneca).

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Abrilada was the fifth adalimumab biosimilar to be approved by the FDA. It, like its competitors, is not yet available on the US market because of licensing agreements signed with the manufacturer of the reference product, AbbVie.

ADALIMUMAB BIOSIMILARS APPROVED BY THE FDA

Manufacturer

Brand Name & Designation

Filing Date

Approval Date/Marketing Status

Amgen

Amjetiva (adalimumab-atto)

November 25, 2015

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

Boehringer Ingelheim

Cyltezo (adalimumab-adbm) 

January 18, 2017

Approved August 29, 2017; Signed licensing agreement with AbbVie to launch July 2023

Sandoz

Hyrimoz (adalimumab-adaz)

January 16, 2018

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

Samsung Bioepis

Hadlima (adalimumab-bwwd)

September 27, 2018

Approved July 22, 2019; Signed licensing agreement with AbbVie to launch June 2023

Pfizer

Abrilada (adalimumab-afzb)

Q4 2018

Approved November 18, 2019; Signed licensing agreement with AbbVie to launch November 2023

Mylan/Fujifilm Kyowa Kirin Biologics

Hulio (adalimumab-fkjp)

Q4 2019

Approved July 6, 2020; Signed licensing agreement with AbbVie to launch August 2023

ADALIMUMAB BIOSIMILARS IN DEVELOPMENT
Company Name Product Name Stage of Development
Coherus Biosciences CHS-1420 Submitted 351(k) application December 2020; FDA decision expected Q4 2019
Fresenius Kabi MSB11022 Completed phase 3 study; FDA filing may occur in 2021
Celltrion CT-P17 Phase 3 trials completed; FDA filing may occur in 2021

Adalimumab Biosimilar Approval for Mylan and Fujifilm Kyowa Kirin

(July 6, 2020) On July 6, the Food and Drug Administration approved partners Mylan/Fujifilm Kyowa Kirin Biologics’ biosimilar version of adalimumab for use in patients with autoimmune diseases.

Pfizer Reaches Milestone: FDA Approves 25th Biosimilar in US

(November 20, 2019) Pfizer announced November 18th that the biosimilar licensing application (BLA) for its adalimumab biosimilar was approved by the Food and Drug Administration (FDA).

Momenta Drops Out of Biosimilar Adalimumab Competition

(August 5, 2019) “Today, Momenta announced the Company will cease active development of M923 at this time, due to changes in the market opportunity associated with Humira patent litigation settlements,” according to a company press release.

The Biosimilar Mabs Have It: FDA Approves Samsung Bioepis' Adalimumab

(July 24, 2019) In a busy beginning of the week, the US Food and Drug Administration approved new biosimilars for Humira and RituxanSamsung Bioepis gained approval for Hadlima™ (adalimumab-bwwd), and Pfizer scored with Ruxience™ (rituximab-pvvr).

Samsung Bioepis Signals a Settlement With Genentech on Herceptin Biosimilar

(July 12,  2019) Samsung Bioepis and Genentech filed a motion in District Court to drop all pending patent litigation regarding Ontruzant, an approved Herceptin biosimilar.

Boehringer Ingelheim Gives up the Fight, Signs AbbVie Agreement on Adalimumab

(May 15, 2019) This agreement allows Boehringer Ingelheim to enter the marketplace July 1, 2023, getting a slight jump on some other licensees, but it effectively ends the protracted patent litigation that Boehringer hoped to win.

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.

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The Promise of Biosimilars

Clinical Trials of Hulio

Phase 3 Trials

Fujifilm Kyowa Kirin conducted a phase 3 double-blind, randomized study, with an open-label switching extension.

 

Genovese MC, Glover J, Greenwald, et al. FKB327, an adalimumab biosimilar, versus the reference product: Results of a randomized, Phase III, double-blind study, and its open-label extension. Arthritis Res Ther. 2019;12:281-292.

This study was conducted in the US, Germany, Ukraine, Russia, Peru, Romania, Spain, Chile, Czech Republic, and Poland. A total of 730 patients with rheumatoid arthritis (RA) were enrolled to receive either FKB327 or Humira. In this first phase of the study, patients received subcutaneous injections of 40 mg every other week of either drug for 28 weeks. In the second phase, an open-label extension study, patients could continue to receive the biosimilar or switch to the biosimilar for up to 76 weeks. Patients were required to be maintained on a stable dose of methotrexate and folic acid throughout the trial period.

Exclusion criteria included, among others, previous treatment with adalimumab or more than one biologic disease-modifying antirheumatic agent or prior use of a TNF inhibitor. The primary outcome measure was the response rate based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 24. Secondary outcome measures included ACR50, ACR70, and DAS28 ratings over time, and safety, and immunogenicity assessments.

A total of 661 patients completed the double-blind study phase (366 treated with FKB327 and 362 with Humira; mean age, 53.3 yr), and 88.4% of those patients participated in the open-label extension trial. Mean DAS-CRP score at baseline was 25.8 for the total population, and there were no significant demographic or symptom differences between the two groups.

The main results from the full-analysis set are described in the Table below:

Variable

FKB327 (n = 366)

Humira (n = 362)

ACR20 (wk 24)

77.1%

79.3%

ACR50 (wk 24)

49.0%

49.4%

ACR70 (wk 24)

21.3%

25.1%

DAS28-CRP (wk 24)

3.43

3.42

Treatment-Emergent Adverse Events (TEAEs)  (through wk 76)

62.2%

66.2%

Serious TEAEs
(through wk 76)

5.3%

7.2%

Presence of Antidrug Antibodies (wk 24)

57.7%

55.5%

The investigators reported that the results seen in the full analysis set were comparable, without any significant differences. Nor did they find any meaningful differences in terms of time to improvement. Discontinuation of treatment because of TEAEs occurred in 5.9% and 4.5% of patients taking FKB327 and Humira, respectively, through the end of phase 2.

In phase 2, they noted, efficacy was maintained through the study’s completion, with comparable ACR20, ACR50, and ACR70 rates among the four groups (those who continued on the biosimilar or on the reference product and those who switched to the biosimilar or to the reference product). Based on the similarity of the results of FKB327 and Humira, the researchers concluded that FKB327 is noninferior to the reference product in the treatment of patients with RA.

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