How many FDA approved Interleukins are there?

Introduction to Interleukins
Interleukins are a family of small glycoproteins that function as essential cytokines, mediating communication between cells of the immune system. They play critical roles in both innate and adaptive immunity and have been studied extensively for their ability to modulate inflammatory responses, promote cell proliferation, and regulate the balance between different immune cell types.

Definition and Role in the Immune System
Interleukins are defined as messenger molecules produced predominantly by leukocytes (such as lymphocytes, monocytes, macrophages, and others) that regulate various aspects of the immune response. Their actions include activation, differentiation, and proliferation of immune cells, and they help coordinate the complex interplay between different cell populations. For instance, interleukin-2 (IL-2) is pivotal for the clonal expansion of T cells, whereas interleukin-11 (IL-11) is involved in stimulating megakaryocyte maturation, which is critical for platelet production. These molecules are integral to both normal immune homeostasis and the pathogenesis of various immune-mediated diseases.

Overview of Interleukin Functions
Interleukins perform a wide range of functions. They can be proinflammatory, as seen with interleukin-1 (IL-1) or interleukin-6 (IL-6), or they may exhibit antiinflammatory properties, such as interleukin-10 (IL-10). Their effects vary depending on the target cell type, the receptor distribution on these cells, and the local microenvironment. Despite this diversity, only a subset of these naturally occurring proteins has been harnessed clinically as therapeutic agents. In clinical practice, a clear differentiation is made between interleukins as natural cytokines and the drugs designed to either mimic or inhibit their actions. In the context of direct interleukin therapeutics, the emphasis is on using the cytokine itself rather than antibodies, receptor antagonists, or modified fusion proteins.

FDA Approval Process
The approval process by the U.S. Food and Drug Administration (FDA) for drugs—including biologic products such as interleukins—is rigorous and multifaceted. It ensures that any approved therapeutic is both safe and effective for its intended use.

Criteria for Drug Approval
The FDA requires that any new drug undergo a thorough evaluation of its pharmacokinetics (PK), pharmacodynamics (PD), clinical efficacy, and safety. This involves:
- Preclinical Studies: In vitro and in vivo studies that characterize the drug’s mechanism, toxicity profile, and pharmacological action.
- Clinical Trials: A series of phased clinical trials where the drug’s safety and efficacy are evaluated in human subjects. These phases are designed to progressively expand the studied population and gather sufficient data that confirm clinical benefits outweigh the risks.
- Manufacturing and Quality Control: For biologics, in particular, the FDA also assesses the manufacturing process, the consistency of product batches, and the overall product quality.

Specifics for Biologics like Interleukins
For biologic agents such as interleukins, the approval process must also account for:
- Structural Complexity: Because interleukins are proteins, their three‐dimensional structure, post‑translational modifications, and aggregation states are critical factors.
- Immunogenicity: Since these proteins can trigger immune responses against themselves, evaluating immunogenicity is paramount.
- Consistency of Production: Given that biologics are produced through living systems or recombinant technology, the manufacturing process must be robust and reproducible.

Biologics are judged not just on their clinical outcome but also on their comparability with the natural molecule or any prior approved formulation. The FDA’s guidance documents emphasize that the totality of evidence from analytical, non‑clinical, and clinical studies must be linked together to support both safety and efficacy.

List of FDA Approved Interleukins
When discussing FDA approved interleukins, it is important to distinguish between the cytokines themselves and the growing number of drugs that target interleukin pathways. Although many marketed biologics interfere with interleukin signaling—such as monoclonal antibodies against IL‑4, IL‑5, IL‑6, IL‑17, IL‑23, and IL‑31—the question here pertains to interleukins that are employed directly as therapeutic agents.

Approved Interleukins and Their Indications
There are exactly two interleukin-based agents that have received FDA approval as therapeutic cytokines:

1. Interleukin‑2 (IL‑2):
- Therapeutic Product: Aldesleukin (commercially known as Proleukin).
- Indications: Aldesleukin is approved for the treatment of metastatic renal cell carcinoma (RCC) and metastatic melanoma. Its mechanism of action centers on the stimulation of immune effector cells, particularly T cells, which can then target and attack cancer cells.
- Mechanism Details: IL‑2 plays a dual role—it not only promotes the proliferation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells but, at lower doses, preferentially expands regulatory T cells (Tregs). However, in high‑dose regimens used for cancer therapy, the focus is on bolstering the immune response against tumor cells.

2. Interleukin‑11 (IL‑11):
- Therapeutic Product: Oprelvekin (brand name Neumega).
- Indications: Oprelvekin is approved for the prevention of chemotherapy-induced thrombocytopenia. It is indicated to stimulate the production of platelets by promoting the maturation of megakaryocyte progenitors.
- Mechanism Details: IL‑11 acts on the IL‑11 receptor (IL‑11Rα) and through the common gp130 signaling pathway to promote platelet production, a mechanism that has proven beneficial in patients undergoing chemotherapy, who are at risk of low platelet counts.

It is important to note that while numerous drugs exist that target interleukin signaling (for example, anti‑IL‑5 antibodies like mepolizumab or anti‑IL‑17 agents like secukinumab), these drugs are not interleukins per se and therefore do not count toward the total of FDA approved interleukins when considering interleukin‐based cytokine therapies.

Year of Approval and Manufacturers
- Aldesleukin (IL‑2):
The original approval for aldesleukin dates from the early 1990s. As one of the first cytokines approved for immunotherapy, it represented a significant milestone in cancer treatment. The manufacturing and development have been spearheaded by companies that specialize in biologics, ensuring consistency in production and quality control that meets stringent FDA guidelines.

- Oprelvekin (IL‑11):
Oprelvekin was approved by the FDA in the mid‑1990s. Its approval marked the first time a recombinant form of IL‑11 was utilized clinically to manage chemotherapy-induced side effects by stimulating platelet production. It is manufactured by companies with expertise in recombinant protein production and has undergone multiple quality assessments to maintain consistency and patient safety.

The detailed historical records and FDA summaries provided by sources in the synapse library confirm that these two therapeutic cytokines remain the only interleukin molecules directly approved for clinical use by the FDA.

Impact and Applications
The approval of IL‑2 and IL‑11 has had a notable impact on both the clinical management of diseases and on the broader pharmaceutical market, influencing how cytokine therapies are developed, marketed, and integrated into treatment protocols.

Clinical Applications
- Cancer Immunotherapy (IL‑2/Aldesleukin):
Aldesleukin’s approval was groundbreaking because it introduced a cytokine-based approach to cancer treatment. High‑dose IL‑2 therapy has since become a standard option for a subset of patients with metastatic renal cell carcinoma and melanoma. Despite its potential adverse effects due to the stimulation of the immune system, careful patient selection and dosing regimens have allowed IL‑2 to remain a viable treatment option in oncologic practice. The clinical effectiveness of IL‑2 hinges on its ability to induce durable responses in a fraction of treated patients, although the overall response rate is modest. Research continues into optimizing dosing strategies and combination therapies to improve patient outcomes.

- Management of Chemotherapy-Induced Thrombocytopenia (IL‑11/Oprelvekin):
Oprelvekin has provided a proactive approach to prevent thrombocytopenia—a common and serious side effect of many chemotherapy regimens. By stimulating megakaryocyte maturation, oprelvekin helps maintain platelet counts, thereby reducing the need for platelet transfusions and allowing patients to continue their chemotherapy without delays. This has improved patient quality of life and reduced morbidity in individuals undergoing highly myelosuppressive treatments.

Market Impact and Future Prospects
The introduction of these FDA approved interleukins has had several downstream effects on the pharmaceutical industry and on clinical practice:
- Catalyst for Cytokine Therapies:
The approval of IL‑2 and IL‑11 paved the way for further exploration of interleukin biology in therapeutics. Their success has led to extensive research into modified interleukins, fusion proteins, and selective receptor agonists/antagonists targeting specific interleukin pathways. Although many of these later developments have taken the form of antibodies or small molecules rather than the cytokines themselves, the foundational concept remains rooted in the understanding garnered from IL‑2 and IL‑11 therapies.

- Innovation in Biologics Manufacturing:
The successful commercial production of aldesleukin and oprelvekin has established robust manufacturing processes that adhere to FDA standards. This has provided a framework for the production of other complex biologics and biosimilars. The rigorous quality control and consistency required for these products have set benchmarks that continue to influence regulatory guidelines and manufacturing practices in the biologics space.

- Economic and Clinical Benefits:
From a market perspective, the use of IL‑2 and IL‑11 therapies has created niche segments in oncology and supportive care where cost-effectiveness is balanced by the significant clinical benefits provided to patients. For example, while high‑dose IL‑2 therapy requires intensive management due to its side effects, the potential for durable responses in a subset of patients justifies its clinical use. Similarly, oprelvekin’s role in thrombocytopenia prevention has reduced hospital stays and additional interventions, contributing to overall healthcare cost savings.

- Future Research Directions:
The clinical limitations of high‑dose IL‑2, including its narrow therapeutic index and toxicity profile, have spurred ongoing research into engineered cytokine variants. These next‑generation molecules aim to retain the beneficial effects of the native cytokine while mitigating adverse effects through chemical modification, combination therapy, or alternative dosing strategies. Similarly, efforts continue to refine IL‑11–based therapies to maximize efficacy in thrombocytopenia without compromising safety.

Conclusion
In summary, after a comprehensive review based on reliable data from the synapse source and multiple regulatory documents, it is clear that there are exactly two FDA approved interleukins used as direct therapeutic agents: interleukin‑2 (administered as aldesleukin, known commercially as Proleukin) and interleukin‑11 (administered as oprelvekin, known commercially as Neumega). These approvals—one for the stimulation of immune effector cells in oncology and one for the prevention of chemotherapy-induced thrombocytopenia—represent significant milestones not only in immunotherapy but also in the advancement of biologics manufacturing and quality control.

This answer has provided a general overview of interleukins, detailed the FDA’s approval process and its specific requirements for biologics, and then enumerated and described the two FDA approved interleukin agents along with their clinical indications, years of approval, and manufacturing details. Finally, the broader market impact and future prospects for interleukin therapeutics were discussed. These interleukins have not only transformed clinical practice in their respective niches but also catalyzed further innovations in cytokine and biologic research. Continued research into modified interleukins and combination therapies promises to expand our therapeutic repertoire, although the core fact remains that—as of now—only IL‑2 and IL‑11 have reached the benchmark of FDA approval as interleukin cytokine therapies.