Avasola

Product Profile:

Infliximab-axxq (Avasola)

Drug Category: Anti-TNF/Autoimmune

Target Indications: Crohn’s disease (adult and pediatric), ulcerative colitis, rheumatoid arthritis, plaque psoriasis, ankylosing spondylitis, psoriatic arthritis

Will be manufactured and marketed by Amgen

Summary: Avasola was the fourth FDA-approved biosimilar version of infliximab (reference product, Remicade®,  which is manufactured by Janssen Pharmaceuticals). It will be the third infliximab biosimilar to be marketed.

Originally designated ABP-710, Amgen filed a biologic license application for approval via the 351(k) biosimilar pathway in December 2018, and the Food and Drug Administration (FDA) approved the biosimilar in December 2019.  Although Amgen did not designate a launch date, it is presumed to be in the near future, as infliximab is not subject to any remaining patent litigation. As the third inflximab biosimilar to reach the market, it will fact stiff competition: Janssen has been aggressively seeking to retain marketshare; the other two biosimilars have been available since 2016 and 2017, respectively; and one of its biosimilar competitors, Celltrion, is testing an investigational subcutaneous formulation of Inflectra, which was approved for use in the EU in November 2019. If a BLA is completed for the US market, the SC formulation will likely not be filed as a 351(k) biosimilar but a 351(a) biologic.

About the Manufacturer

Amgen, based in Thousand Oaks, California is a leading 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 six biosimilars. Besides Avasola, these include the approved products Mvasi (bevacizumab-awwb), Kanjinti (trastuzumab-anns), and three products in earlier stages of the pipeline (rituximab, cetuximab, and eculizumab).

Amgen and Allergan formed a collaboration in December 2011 to develop and commercialize four oncology biosimilar products (which does not include Avasola). In this partnership, Amgen takes the lead for developing and manufacturing the products as well as directing the marketing efforts.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

BIOSIMILARS APPROVED BY THE FDA: FDA FILING DATES AND ACTIONS

Biosimilar

Manufacturer

Brand Name & Designation

Innovator Product

FDA Filing Date

Status

Infliximab

Celltrion/Pfizer

Inflectra (infliximab-dyyb)

Remicade

August 8, 2014

Approved April 5, 2016; marketed

Infliximab

Samsung Bioepis/Merck

Renflexis (infliximab-abda)

Remicade

May 23, 2016

Approved April 21, 2017; marketed

Infliximab

Amgen

Avasola (infliximab-axxq)

Remicade

December 18, 2018

Approved December 6, 2019, not yet marketed

Updated February 1, 2020.

Infliximab Biosimilar(s) in Development

Company name, Country

Product name

Stage of development

Nichi-Iko Pharmaceutical,  Japan

NI-071

Phase III trial in rheumatoid arthritis expected to be completed in March 2015. Approved in Japan in September 2017. US phase III trial in rheumatoid arthritis expected to be completed February 2019

Merck to Spin Off Company That Will Include Its Biosimilar Marketing in 2021

(February 7, 2020) On February 5, Merck announced that it will create a new spinoff that will include its biosimilar business with Samsung Bioepis as well as its legacy pharmaceuticals (e.g., Zetia®, Vytorin®, and other widely diversified brands).

Amgen’s Infliximab Biosimilar, Avasola, Receives FDA Approval

(December 9, 2019) The FDA announced approval of Amgen’s infliximab biosimilar Avasola. Avasola will be the third infliximab biosimilar agent to be marketed.

The Implications of Celltrion’s Development of a Subcutaneous Infliximab

(November 26, 2019) Celltrion received approval today in the European Union (EU) for its subcutaneous (SC or SubQ) form of infliximab (Remsima®, marketed as Inflectra® in the US) for treating rheumatoid arthritis. Currently, infliximab is available only as an office-based infusion.

Implications of UnitedHealthcare’s Preference of Remicade and Neulasta to Their Biosimilars

(May 30, 2019) Effective July 1, 2019, approximately 22.5 million commercial and 6 million Medicaid UHC members will not be able to access these biosimilars without trying the reference agents first (virtually eliminating biosimilar use).

Amgen Submits Application for Biosimilar Inflximab

(December 17, 2018) ABP 710 was the subject of a phase 3 trial in patients with moderate-to-severe rheumatoid arthritis.

Infliximab Biosimilars Savings Could Exceed $400 Million Dollars Annually

(June 21, 2018) Everyone with an opinion believes that biosimilar drug use will save the health system considerable money. Calculations for biosimilar savings have been hampered by several factors. For example, previous high estimates have not been based on real-life scenarios.

How Will Biosimilars Be Affected by Trump’s Drug Price Reform Measures?

(May 14, 2018) When President Trump announced the broad strokes of his drug price reform initiative, some of these measures seemed on target to benefit the biosimilars industry. However long awaited, makers of originator biologics seemed not to be worried about its implications. The President may not be able to effect much change, without causing unintended adverse consequences

Plans Use Step Therapy to Encourage Utilization of Remicade Over Biosimilars

(May 9, 2018) Health plans and insurers are not yet turning to biosimilar infliximab as a preferred therapy, according to Gillian Woollett, DPhil, MA, of Avalere. Her new report surveyed publicly available policy about health plans across the nation. The principal finding was that step therapy was commonly used  to encourage use of the originator product.

Celltrion and Inflectra, Mylan and Botox, and a Biosimilar Blooper

(March 2, 2018) The second quarter is expected to be rife with news regarding Food and Drug Administration approval decisions on a biosimilar for rituximab and two pending applications for trastuzumab. Although biosimilars have not generated much news of importance lately, we wrap up the week with some items of interest.

Pfizer US Biosimilar Revenues Growing Slowly, Better News Internationally

(February 2, 2018) According to an article posted on the Market Realist website, Pfizer’s US and global biosimilars revenues are growing, but its sales of Inflectra remains stunted.

Pfizer’s At-Risk Launch of Inflectra Pays Off (at Least a Bit)

(January 25, 2018) The US Court of Appeals handed Pfizer a big victory in its gamble to bring its biosimilar version of Remicade® to the market before the completion of patent litigation.

A Health System Biosimilar Survey’s Implications

(December 18, 2017) On December 14, Pfizer got an early Christmas present, the approval by the Food and Drug Administration (FDA) of the second infliximab biosimilar in which it has a stake.

A Health System Biosimilar Survey’s Implications

(November 30, 2017) When asked about potential cost savings with the infliximab biosimilar, nearly one-quarter of health system respondents did not believe that it represented a cost savings opportunity for their organization, according to a newly published survey in the Journal of Managed Care and Specialty Pharmacy.

News in the Courts on Biosimilars

(November 14 2017) According to a Reuters report, Janssen Biotech withdrew its patent lawsuit against Samsung Bioepis on November 10. The suit alleged infringement in the manufacture of Samsung’s infliximab biosimilar. The action, which was filed in U.S. District Court of New Jersey, means that Merck and Samsung, which launched Renflexis™ in July, is no longer at risk…

Pfizer Sues J&J on Anticompetitive Practices on Infliximab in the US

(September 20, 2017) In late May, Merck was named in a UK lawsuit by Pfizer, which has been trying to expand its market for Inflectra®. Merck, which markets Remicade® (infliximab) in the EU, was accused of anticompetitive practices.

Inflectra Sales Lagging for Pfizer in Second Quarter

(August 4, 2017) Pfizer announced some disappointing results for the second quarter in its quest to advance a foothold in the biosimilar market. The second-quarter results hinted at more difficulties to come for the Inflectra® brand, with the most recent launch of Merck’s Renflexis®.

Living With Crohn's Disease

Understanding Biosimilars

Clinical Trials of Avasola

Published Trial Results

Avasola’s clinical trial program consists of one phase 3 clinical trial comparing the biosimilar with the reference product for the treatment of rheumatoid arthritis  and phase 1 investigations in healthy volunteers. The results of phase 3 trial are featured here.

Study to Assess if ABP 710 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis Compared to Infliximab

 This randomized, double-blind phase 3 study of ABP 710 sought to compare the clinical efficacy and safety of the biosimilar to the reference product Remicade. The investigators also incorporated a switching component into the design of the rheumatoid arthritis study.

 All patients had symptoms of moderate-to-severe disease. Patients were given methotrexate 7.5–25 mg/wk along with biosimilar or reference infliximab in 3 mg/kg-infused doses. The primary study endpoint was the percent of patients attaining 20% improvement in symptoms according to the American College of Rheumatology 20 (ACR20) criteria at week 22. The secondary clinical endpoints were the DAS28-CRP score improvement and safety at week 22, as well as the percentage attaining ACR50 and ACR70. After 22 weeks, study subjects who had been randomized to receive Remicade were re-randomized to either continue with this therapy or switch to ABP 710. Participants initially randomized to ABP 710 continued receiving ABP 710. In this extended study, clinical parameters were measured through 50 weeks of therapy.

Five hundred fifty-six patients were randomized to receive ABP 710 (n = 278) or the originator product (n = 278). Of those receiving the biosimilar, 68.1% attained ACR20 compared with 59.1% of those administered the reference product. At 50 weeks, 67.6% of those remaining in the biosimilar arm attained ACR20, compared with 72.7% of those remaining in the reference arm and 70.6% of those switched from Remicade to ABP 710. This result firmly supported noninferiority of ABP 710 to Remicade for the primary endpoint.

In terms of ACR50 at 22 weeks, 43.0% and 36.2% of those taking the biosimilar and the reference product, respectively, attained this score. At 50 weeks, 49.2% of those remaining in the biosimilar arm attained ACR50, compared with 54.5% of those remaining in the reference arm and 57.1% of those switched from Remicade to ABP 710. At week 22, ACR70 was reached by 24.0% in the biosimilar group and 19.7% in the reference drug group. At week 50, 34.0% of those remaining in the ABP 710 group attained ACR70, 32.2% of those continuing to receive Remicade did so, compared with 43.7% of those switched to the biosimilar.

The DAS28-CRP scores did not vary between groups at week 22, and score improvements differed by only 0.19 among the three groups by week 50.

The percentage of subjects reporting any serious adverse events by week 50 ranged from 0.84% for those switched to the biosimilar to 6.22% for those continuing with ABP 710. No one type of serious adverse event dominated, according to the study results. Other adverse events occurred in 11.5% to 25.2% of patients, with upper respiratory tract infections being most common. The presence of neutralizing antibodies were not significantly different among study groups.

The researchers concluded that Avasola (ABP 710) is sufficiently similar to the reference product, in terms of efficacy and safety.

Important Links and Resources

Information About Biosimilars

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US Biosimilars Filing Status

*This biosimilar is not yet available for prescription.

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