Steroid sparing and steroid avoidance have become important issues in modern medicine due to the toxic side effects of many common glucocorticoid therapies used to treat conditions ranging from rheumatoid arthritis to organ failure. In clinical trials, this creates an urgent need to quantify the toxic effects of new drugs more carefully in order to understand the benefits of steroid-sparing therapeutics.
When they were first introduced more than half a century ago, glucocorticoid medicines were hailed as Nobel-prize worthy discoveries for their ability to mimic the body’s own stress hormones and reduce the symptoms of inflammation. But such powerful reactions can come with a downside – causing side effects such as fluid retention, bone damage, elevated blood sugar levels, mood disorders, mania and memory loss.
In some cases, when high doses of glucocorticoids are used for long periods of time, the risks can outweigh the benefits of the treatment. Consequently, physicians are increasingly seeking ways to reduce or eliminate glucocorticoids, and pharmaceutical companies continue looking to develop steroid-sparing alternative therapies to treat a variety of conditions.
A number of new steroid-sparing biologic drugs are available that help reduce the dosage of steroids and modulate the immune system’s reaction to their use. However, until recently, physicians and investigators in clinical trials didn’t have tools that could quantify the negative effects of steroids or measure the effectiveness of steroid-sparing therapies.
Steroid sparing to avoid toxicity
The Glucocorticoid Toxicity Index (GTI) is an instrument that can be used in clinical trials and drug development to quantify the adverse effects of corticosteroids and measure the relationship between steroids and side effects.
Considering glucocorticoid toxicity in the Target Product Profile (TPP) over the course of a clinical development program can help clinicians and pharmaceutical companies document the potential benefit a therapy offers in reducing steroid-related toxicity, even as steroid use is reduced.
The GTI helps quantify the effectiveness of steroid-sparing therapies in specific ways as outlined by the Target Product Profile (TPP).
“Steroid-sparing therapies and steroid avoidance continue to be important topics due to the high number of patients affected by diseases with treatments that can lead to steroid toxicity,” said Dr Paul Brunetta, Head of Clinical and Translational Medicine at Sana Biotechnology.
Adding glucocorticoid toxicity measurement to a trial drug’s TPP, especially when the new treatment presents a steroid-sparing alternative, helps ensure adequate data are collected. GTI is a standardized protocol for measuring toxicity to ensure all researchers measure it the same way and understand why it matters.
What is a Target Product Profile (TPP)?
A target product profile (TPP) outlines the desired 'profile' or characteristics of a target product that is aimed at a particular disease or diseases. A TPP states the intended use, target populations and other desired attributes of a product, including safety and efficacy-related characteristics.
The TPP acts as a planning tool that helps guide the cross-disciplinary internal team in making decisions and ensuring development focuses on the desired characteristics. In addition, TPPs support the regulatory effort by framing the submission in a consistent and measurable way.
When GTI data are used as part of the TPP the GTI can be viewed as both an outcome measure, and a marketing tool.
Why do you need a TPP?
In drug development and testing, a TPP helps define success: specifically, it creates a clear picture of what success looks like in the clinic. It allows different areas of a biotech or company — including research, development, and commercial aspects – to stay focused on the core definition of product success using specific measurable elements: efficacy, safety, dosage, and administration.
The TPP creates a blueprint that everyone can understand. It supports:
- Research: to define and prioritize targets or programs
- Development: to define the CDP (clinical development plan)
- Commercialization: to define the market opportunity
It’s also a tool that can enhance regulatory communication. The FDA has draft guidance related to TPP, so regulators understand that it can be an important tool in creating high-efficacy, low-risk drugs.
“A key objective in interactions between the pharmaceutical industry and regulatory authorities is to achieve clarity on the goals and expectations for the drug development process. In the United States, the Target Product Profile (TPP) is a tool to facilitate communication between the pharmaceutical industry and the FDA, as well as between stakeholders in and outside of the industry.” (Tyndall, Du and Breder)
How do you create a TPP?
The creation of the TPP includes all parts of the organization that are involved with the lifecycle of a new therapy from research to development to regulatory submission. The TPP is a draft document; it’s iterative and meant to evolve as new information is gathered (such as competitor data or new safety findings).
Companies gather feedback on the TPP from patients, physicians, payors and healthcare systems. The input and new information can help define the Go/No Go criteria for the product to determine if it’s a viable commercial endeavor.
Incorporating toxicity information into the TPP helps establish the target profile around the safety of the therapy. For example, if the company were to say that a particular drug significantly reduces glucocorticoid toxicity above the minimally clinically important difference, that could be considered either in the optimal or in the target profile for a particular therapy.
Learn more about steroid-sparing and TPPs
Including a Glucocorticoid Toxicity Index (GTI) as part of all TPPs helps add valuable information to a company’s understanding of steroid toxicity and therapies for steroid-sparing.
Watch this on-demand webinar on GTI and TPPs, featuring Dr Paul Brunetta, Head of Clinical and Translational Medicine, Sana Biotechnology, and Dr John H Stone MD MPH, Professor of Medicine at Harvard Medical School, and Edward A. Fox Chair, Medicine, Massachusetts General Hospital.