Unraveling the Scientific Journey: Who Discovered Anakinra?

The journey of anakinra, a life-changing medication for patients with severe inflammatory diseases, is rooted in fundamental scientific discovery decades ago. While a pharmaceutical giant first brought it to market, the actual discovery involves a fascinating collaborative effort among independent academic researchers and a trailblazing biotech company to answer the question of who discovered anakinra.

Quick Summary

Anakinra's origin lies in the independent discovery of the human protein IL-1Ra by researchers William Arend and Jean-Michel Dayer in the mid-1980s. Its subsequent development was led by the biotech company Synergen, which was later acquired by Amgen, and its commercialization was eventually licensed to Swedish Orphan Biovitrum (Sobi).

Key Points

• Initial Scientific Discovery: The protein interleukin-1 receptor antagonist (IL-1Ra) was independently discovered by two separate research teams led by William Arend and Jean-Michel Dayer in the mid-1980s.

• Biotech Commercialization: The biotech startup Synergen developed the recombinant version of IL-1Ra, named anakinra, but failed with its initial sepsis trials.

• Amgen's Role: Amgen acquired Synergen in 1994, continued the drug's development for rheumatoid arthritis, and secured its FDA approval in 2001.

• Current Marketing: The commercial rights for Kineret (anakinra) were later licensed to Swedish Orphan Biovitrum (Sobi), who now markets the drug.

• Broadened Therapeutic Scope: Beyond its initial approval for RA, anakinra has gained approvals for rare autoinflammatory diseases like CAPS and DIRA, highlighting the medication's versatility.

• IL-1 Blocking Action: The core mechanism involves anakinra blocking the pro-inflammatory cytokine interleukin-1 by competitively inhibiting its binding to cellular receptors.

• A Legacy of Collaboration: The story of anakinra's development highlights a complex journey involving academic researchers, biotech startups, large pharmaceutical companies, and ongoing clinical research to unlock its full potential.

The Scientific Breakthrough: The Discovery of IL-1Ra

The foundation of anakinra lies in the identification of a natural human protein in the mid-1980s. This protein, known as the interleukin-1 receptor antagonist (IL-1Ra), was found to counteract the inflammatory effects of interleukin-1 (IL-1). Two researchers independently made this significant discovery:

• William Arend: A rheumatologist at the University of Washington, Arend and his team identified a protein that bound to the same receptors as IL-1 but did not cause inflammation. Their findings were published in 1985.
• Jean-Michel Dayer: Working in Switzerland, Dayer also discovered the same protein around the same time, with his research published in 1984.

Their independent discoveries established the basis for a new class of anti-inflammatory treatments by showing that the body naturally regulates IL-1's inflammatory power.

The Commercialization Path: From Synergen to Amgen

Transforming the discovery of IL-1Ra into a therapeutic drug involved the biotechnology sector. Synergen, a biotech startup based in Boulder, collaborated with Arend after recognizing the potential of IL-1Ra.

Synergen successfully produced a recombinant version of human IL-1Ra, named anakinra, using E. coli bacteria. This recombinant protein differed slightly from the natural version by having an extra methionine residue.

Initially, Synergen explored treating severe sepsis in the early 1990s. However, despite initial positive results, anakinra did not succeed in Phase III clinical trials for this condition. This led to Synergen being acquired by Amgen in 1994.

Amgen continued the development of anakinra, shifting focus to rheumatoid arthritis (RA). After extensive trials, Kineret (anakinra) received FDA approval for RA treatment in 2001. Later, in 2008, Amgen licensed the commercial rights for Kineret to Swedish Orphan Biovitrum (Sobi).

Expanded Indications and Broader Therapeutic Use

Despite facing market competition initially, ongoing research demonstrated anakinra's effectiveness for rare and severe autoinflammatory conditions. Its safety profile and specific action mechanism have made it an important treatment option.

Key developments in anakinra's history include:

• 1984–1985: Discovery of IL-1Ra by Dayer and Arend.
• Early 1990s: Synergen's development and trials for sepsis.
• 1994: Amgen acquires Synergen.
• 2001: FDA approves Kineret for RA.
• 2008: Amgen licenses commercial rights to Sobi.
• 2012–2013: Approvals for CAPS, including NOMID.
• 2020: FDA approval for DIRA.
• 2022: FDA grants EUA for severe COVID-19 cases in hospitalized patients.

Anakinra vs. Other IL-1 Inhibitors: A Comparison

Aspect	Anakinra	Rilonacept	Canakinumab
Mechanism	Recombinant IL-1 Receptor Antagonist	IL-1 Trap (fusion protein with IL-1 binding domain)	Human Monoclonal IL-1β Antibody
Administered	Subcutaneous daily injection	Subcutaneous weekly injection	Subcutaneous injection every 8 weeks
Initial FDA Approval	2001 (for RA)	2008 (for CAPS)	2009 (for CAPS)
Molecular Form	Recombinant, non-glycosylated protein	Fusion protein	Monoclonal antibody
Half-life	Short (approx. 4–6 hours)	Moderate (approx. 8.6 days)	Long (approx. 26 days)
Key Advantage	Rapid onset of action	Longer dosing interval	Longest dosing interval

Conclusion: A Collaborative and Evolving Legacy

Anakinra's journey illustrates that the development of significant medications often involves multiple stages and collaborations over many years. It started with the independent scientific insights of Arend and Dayer, moved through the development and commercialization efforts of biotech firms Synergen and Amgen, and is now handled by Sobi, specializing in rare diseases. The drug's application has expanded from rheumatoid arthritis to critical therapies for rare autoinflammatory conditions and even severe COVID-19, highlighting the lasting importance of fundamental scientific discovery. Its history exemplifies how understanding the body's natural processes can lead to effective treatments for challenging medical conditions.

Learn more about the specific mechanisms of action for interleukin-1 antagonists and their clinical applications from authoritative sources like the National Institutes of Health (NIH).

Frequently Asked Questions

Was Anakinra developed solely by Amgen?

No, while Amgen brought anakinra to market, the drug was originally developed by the smaller biotech startup Synergen, which Amgen later acquired.

What is the key scientific discovery that led to anakinra?

The key discovery was the identification of the human protein IL-1 receptor antagonist (IL-1Ra) by William Arend and Jean-Michel Dayer in the mid-1980s. This protein naturally counteracts the inflammatory effects of IL-1.

Who markets anakinra today?

Currently, the commercial rights for anakinra (brand name Kineret) are held and marketed by the Swedish pharmaceutical company Swedish Orphan Biovitrum (Sobi), which acquired them from Amgen in 2008.

Why did Synergen initially fail with anakinra?

Synergen's initial clinical trials for anakinra were focused on treating severe sepsis. The drug failed to show significant effectiveness in late-stage trials for this indication, which contributed to Synergen's acquisition by Amgen.

What is the mechanism of action for anakinra?

Anakinra works by blocking the biological activity of interleukin-1 (IL-1), a pro-inflammatory cytokine. It does this by competitively inhibiting IL-1's binding to its receptor, thereby preventing the inflammatory cascade from being triggered.

When was anakinra first approved by the FDA?

Anakinra was first approved by the U.S. Food and Drug Administration (FDA) in 2001 for the treatment of rheumatoid arthritis in adults.

For what conditions is anakinra used today?

Anakinra is approved for treating rheumatoid arthritis and several rare autoinflammatory diseases, including Cryopyrin-Associated Periodic Syndromes (CAPS) and Deficiency of Interleukin-1 Receptor Antagonist (DIRA). It is also used off-label for other conditions and received an emergency use authorization for severe COVID-19 cases.