What was Geref? (Sermorelin Acetate)
Geref, the brand name for sermorelin acetate, was a synthetic peptide analogue of growth hormone-releasing hormone (GHRH). It was used to treat growth hormone deficiency (GHD) in children by stimulating the pituitary gland to produce and release natural growth hormone (GH). The medication received approval from the U.S. Food and Drug Administration (FDA) in 1997 for this specific indication. Unlike synthetic human growth hormone (somatropin), which replaces GH directly, Geref worked by encouraging the body's own GH production. This difference meant that Geref's effects were more natural and potentially had fewer side effects associated with synthetic GH overdose, such as joint pain or fluid retention.
For many years, Geref served as an important diagnostic tool for assessing pituitary function in children with suspected GHD, in addition to its use as a therapeutic agent. However, its market presence was not long-lived, and its withdrawal from the market has been a point of confusion for many.
The reasons behind Geref's discontinuation
The primary reasons for Geref's discontinuation were related to business and production, rather than any issues with its safety or effectiveness. This is a crucial distinction, as drug withdrawals based on safety issues are a different, more serious matter. EMD Serono, the manufacturer, made the decision to voluntarily stop production in 2008 for two key reasons:
Manufacturing difficulties
EMD Serono cited manufacturing difficulties as a major factor in their decision to discontinue Geref. The specifics of these issues were not widely publicized, but they were significant enough to warrant ceasing the production of the active ingredient. The challenges likely involved complex and costly production processes inherent to manufacturing peptide drugs like sermorelin. Maintaining a consistent, high-quality supply of a peptide-based drug can be technically demanding and expensive, especially for a niche market like pediatric GHD. The increasing complexity and cost of maintaining FDA-approved manufacturing facilities can sometimes outweigh the profitability of older, less-prescribed medications.
Commercial and market factors
The decision was also commercially driven. At the time of Geref's discontinuation, the pharmaceutical landscape for GHD treatment had changed significantly since its approval. Newer, more direct growth hormone products (somatropin) had entered the market and were gaining popularity. These newer therapies often offered different dosing schedules or perceived benefits that made them more commercially attractive for the manufacturer to focus on. With a limited market for Geref and competing alternatives, the investment required to resolve the manufacturing issues and maintain the product's market presence was likely deemed no longer justified.
FDA's official stance on the withdrawal
In 2013, the FDA issued a notice in the Federal Register confirming that Geref was not withdrawn for safety or efficacy reasons. This determination is important because it allows other manufacturers to potentially produce generic versions of the drug, provided they meet all regulatory requirements. The FDA's review of its own records and available literature found no evidence to suggest that the medication was unsafe or ineffective during its time on the market. This official statement dispelled any public speculation that Geref's withdrawal was a result of undisclosed adverse events or performance issues.
Alternatives to Geref for growth hormone deficiency
With Geref no longer an option, patients with GHD transitioned to alternative treatments. These alternatives primarily fall into a few key categories:
- Synthetic Human Growth Hormone (Somatropin): This class of drugs directly replaces the body's deficient GH. Examples include Genotropin, Serostim, and Humatrope. Somatropin is a very effective treatment for GHD and is available in various forms, including daily and some extended-release injections.
- Other GHRH Analogs: While Geref was the original FDA-approved GHRH analog for pediatric GHD, other GHRH-based products like tesamorelin (Egrifta) have been approved for different indications (e.g., HIV-associated lipodystrophy). These are not direct replacements for Geref's pediatric indication but illustrate the continued development in this class of drugs.
- Compounded Sermorelin: After Geref was discontinued, some compounding pharmacies began offering sermorelin. It is critical to understand that this is not the same as the FDA-approved product. Compounded medications are not subject to the same rigorous testing and quality standards as FDA-approved drugs, and their safety and efficacy for GHD are not officially established.
Comparison of Geref and modern treatments
| Feature | Geref (Sermorelin) | Recombinant Human GH (Somatropin) |
|---|---|---|
| Mechanism | Stimulates natural GH release from pituitary gland | Direct replacement of growth hormone |
| Dosing Frequency | Typically administered daily | Daily or extended-release weekly injections available |
| Control | Offers physiological, pulsatile GH release | GH level is constant, not pulsatile |
| Manufacturing | Active ingredient production ceased due to difficulties in 2008 | Advanced, stable recombinant technology |
| Availability | Discontinued; only available via compounding pharmacies | Widely available as several FDA-approved products |
| Side Effects | Typically mild, like injection site pain | More potential side effects, such as joint pain or fluid retention |
| FDA Status | FDA-approved product officially withdrawn in 2008 | FDA-approved and actively marketed |
The impact of Geref's discontinuation
The withdrawal of Geref had several impacts on the medical community and patient care:
- Shift in Treatment Strategy: Clinicians moved away from using a GHRH analog for pediatric GHD and relied more heavily on direct GH replacement therapy (somatropin). This shifted the treatment landscape, focusing on one primary class of therapy rather than offering multiple approaches.
- Diagnostic Challenges: Since Geref was also used as a diagnostic agent, its discontinuation removed one tool for assessing pituitary function. While other diagnostic methods are available, this specific tool was no longer an option.
- Rise of Compounding: The demand for sermorelin, particularly for off-label anti-aging purposes, led to a surge in its availability through compounding pharmacies. This has created confusion for consumers, who may not understand the difference between a discontinued FDA-approved drug and a compounded alternative. It has also raised concerns about quality control and appropriate use.
Conclusion
Geref was not discontinued because it was unsafe or ineffective for its approved indication of pediatric growth hormone deficiency. Instead, its manufacturer, EMD Serono, made a voluntary business decision to stop production in 2008, citing manufacturing challenges and the evolving commercial landscape with new, competing therapies. The FDA confirmed that the withdrawal was not for safety or efficacy reasons, leaving the door open for potential generic versions in the future. While Geref is no longer available as an FDA-approved drug, effective alternatives like recombinant human growth hormone (somatropin) are widely used for GHD, and compounded versions of sermorelin are available through different regulatory pathways.
