Amjevita

Product Profile:

Adalimumab-atto (Amjevita)

Drug Category: anti-TNF inhibitor/autoimmune

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

Manufactured by Amgen; will be marketed by Amgen

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

Originally known as ABP 501, Amgen submitted a biologic license application for approval via the 351(k) biosimilar pathway in November 2015. The Food and Drug Administration (FDA) approved the biosimilar in September 23, 2016. The European Medicines Agency approved Amjevita for use in the EU in March 2017. However, due to patent litigation with Abbvie, the launch was delayed. Amgen signed a licensing agreement with Abbvie, which concludes continuing patent litigation and enabled Amgen to launch in the EU in October 2018. Under the agreement, Amjevita will launch in the US in January 2023, and Amgen will pay royalties to Abbvie on its sales.

About the Manufacturer

Amgen, based in Thousand Oaks, California, is a leading global biotechnology company. The company focuses on six therapeutic areas: cardiovascular disease, oncology, bone health, neuroscience, nephrology and inflammation. Amgen has two reference products that are currently facing biosimilar competition (filgrastim and pegfilgrastim), but they also have five biosimilars. These include the approved product Mvasi (bevacizumab-awwb), two products that have been filed with the FDA for approval (trastuzumab, infliximab), and three products in earlier stages of the pipeline (rituximab, cetuximab, and eculizumab).

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Amjevita 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

 

Manufacturer

Brand Name & Designation

FDA Filing Data

Status

Amgen

Amjevita (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; not yet marketed; signed licensing agreement with AbbVie to launch July 2023

Sandoz

Hyrimoz (adalimumab-adaz)

January 16, 2018

Approved October 31, 2018; not yet marketed; signed licensing agreement with AbbVie to launch Sept 2023

Samsung Bioepis/Merck

Hadlima (adalimumab-bwwd)

September 27, 2018

Approved July 23, 2019; signed licensing agreement with AbbVie to launch in late June 2023

 ADALIMUMAB BIOSIMILARS IN DEVELOPMENT

Company Name

Product Name

Stage of Development

Celltrion

CT-P17

Phase 3 trials to be completed in 2020

Coherus Biosciences

CHS-1420

Completed phase 3 study; FDA submission anticipated Q4 2019. Signed licensing agreement with AbbVie to launch in December 2023

Fresenius Kabi

MSB11022

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

Momenta

M923

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

Mylan/Fujifilm Kyowa Kirin Biologics

FKB327

In development; signed licensing agreement with AbbVie to launch in August 2023

Pfizer

PF-06410293

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

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.

FDA Approves Biosimilars for Adalimumab and Rituxumab

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

FDA Approves Biosimilars for Adalimumab and Rituxumab

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

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.

A Possible Clinical Benefit for Amjevita

(March 31, 2017) According to researchers findings, Amjevita was associated with less injection-site pain compared with Humira, based on pain scores given by clinical trial patients with moderate to severe rheumatoid arthritis.

The FDA Approves First Biosimliar to Humira

(September 23, 2016) The FDA approved the first biosimliar version of adalimumab (reference product, Humira).  The approval extends to six indications of the originator product.

Impressions on the Adalimumab Biosimilar Arthritis Advisory Committee Meeting

(July 12, 2016) 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 Amjevita

Amjevita was tested in phase 1 pharmacokinetic studies as well as three (3) phase III studies. The two phase III studies used for FDA approval were conducted in patients with rheumatoid arthritis and psoriatic arthritis. There was also a phase III long-term safety efficacy trial for patients with rheumatoid arthritis.

Rheumatoid Arthritis

Efficacy and Safety of the Biosimilar ABP 501 Compared With Adalimumab in Patients With Moderate to Severe Rheumatoid Arthritis: A Randomized, Double-Blind, Phase III Equivalence Study.

A total of 526 patients with moderate-to-severe rheumatoid arthritis enrolled in a randomized, double-blind study. The investigators assigned 264 patients to receive ABP 501 and 262 to receive US-licensed Humira, both dosed at 40 mg subcutaneously on day 1 and then every two weeks until week 22. All of the patients demonstrated an inadequate response to methotrexate. All were given concomitant methotrexate and folic acid therapy. The primary efficacy endpoint was attaining a 20% improvement in the American College of Rheumatology (ACR) measurements at week 24.

The researchers reported that at week 24, the ACR20 response was 74.6% in the ABP 501 group and 72.4% in the reference product group. Other 24-week results for ACR50, ACR70, and DAS28 scores are shown in the Table below.

Variable

ABP 501

(N=264)

US-licensed Adalimumab

N=262)

ACR20 (% responders)

74.6%

72.4%

ACR50 (% responders)

49.2% (120/244)

52.0%

(131/252)

ACR70 (% responders)

26.0%

22.9%

Mean change of DAS28-CRP from baseline

-2.32

-2.32

Based on these clinical results, the investigators concluded that the biosimilar was as efficacious as the reference product Humira.

Treatment-emergent adverse events (TEAE) were similar in both groups (50.0% in the ABP 501 group and 54.6% in the US adalimumab group). The most common TEAEs were nasopharyngitis, headache, arthralgia, cough, and upper respiratory infections. Serious adverse events were observed in 3.8% of the patients in the ABP 501 group and in 5.0% in the US-licensed adalimumab group. Antidrug antibodies were seen in 24 of those taking the biosimilar compared with 29 receiving the reference product.

An open-label extension study was conducted in 467 patients who received either ABP 501 or the reference product for a total of 24 months to assess long-term safety and efficacy. The percentage of participants with an ACR20 response was 73.2% in the biosimilar group and 73.3% in the reference product group that had switched to the biosimilar. The change in DAS28-CRP score was -2.26 and -2.25 in the respective groups. Safety results were similar in the two groups, with 143 patients in the ABP 501 group experiencing any adverse event and 154 in the reference product group switching to the biosimilar experiencing an adverse event.

Psoriasis

Clinical Similarity of Biosimilar ABP 501 to Adalimumab in the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blind, Multicenter, Phase III Study

In this randomized, double-blind study 350 patients (175 patients in each study group) with moderate-to-severe plaque psoriasis were assigned to receive either ABP 501 or EU-licensed Humira. The initial trial duration was 16 weeks. Study participants were administered the medications with a loading dose of 80 mg subcutaneously and then a dose of 40 mg subcutaneously every 2 weeks for 16 weeks. The percent improvement in the Psoriasis Area and Severity Index (PASI) score from baseline to week 16 was the primary efficacy point.

At 16 weeks, the mean PASI improvement was 80.9% in the ABP 501 group and 83.1% in the EU-licensed adalimumab group. Other efficacy results at week 16 are shown below.

ABP 501 (N=172)

EU-licensed Adalimumab (N=173)

PASI 50 Response

92.4%

94.2%

PASI 75 Response

74.4%

82.7%

PASI 90 Response

47.1%

47.4%

PASI 100 Response

16.9%

19.7%

Adverse events observed in each of the study groups was similar through week 16 as seen in the Table.

ABP 501

(N=174)

EU-licensed Adalimumab

(N=173)

Any TEAE

117 (67.2%)

110 (63.6%)

Serious AEs

6 (3.4%)

5 (2.9%)

Nasopharyngitis

25 (14.4%)

27 (15.6%)

Headache

13 (7.5%)

18 (10.4%)

Infections

59 (33.9%)

58 (33.5%)

Binding ADAs

96 (55.2%)

110 (63.6%)

Neutralizing antibodies

17 (9.8%)

24 (13.9%)

The investigators concluded that the data accumulated through the trial confirmed that there was overall similarity between the biosimilar and the reference product.

Clinical Similarity of the Biosimilar ABP 501 Compared With Adalimumab After Single Transition: Long-Term Results From a Randomized Controlled, Double-Blind, 52-Week, Phase III Trial in Patients With Moderate-to-Severe Plaque Psoriasis.

In the open-label extension trial, the patients who had at least a PASI 50 response at week 16 were eligible to enroll in this phase, which would continue for 52 weeks of therapy. Those receiving ABP 501 for the first 16 weeks (N=152) continued on that regimen while patients receiving the EU-licensed adalimumab were re-randomized to either continuing on that regimen (N=79) or switching (N=77) to the biosimilar product. At week 50, the mean PASI score improvement was similar across the three groups as were the percentage of responders achieving PASI 50, PASI 75, PASI 90, and PASI 100, with no differences reaching a statistical difference. Adverse events observed in the three study groups were similar as were the percentages of patients with binding and neutralizing antidrug antibodies.

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