What is Synribo?
Synribo is the brand name for the medication with the generic name, omacetaxine mepesuccinate. It was an oncology drug that received accelerated FDA approval in 2012 for the treatment of certain forms of chronic myeloid leukemia (CML). The drug was specifically indicated for adult patients in the chronic or accelerated phase of CML who had developed resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs). However, citing manufacturing issues, the drug was permanently discontinued and is no longer available.
The Mechanism of Action of Omacetaxine Mepesuccinate
Unlike TKIs that target the BCR-ABL protein's enzymatic activity, omacetaxine mepesuccinate works through a different pathway. As a protein synthesis inhibitor, its mechanism of action involves inhibiting the elongation step of protein synthesis. By binding to the ribosomal A-site, it prevents the proper positioning of aminoacyl-tRNAs, thereby blocking protein production.
This unique approach was particularly significant for treating CML because it is effective against both the wild-type and the T315I-mutated forms of the BCR-ABL protein. The T315I mutation is known to confer resistance to most TKIs, making omacetaxine mepesuccinate an important alternative for this specific patient population. In vitro studies demonstrated that omacetaxine mepesuccinate reduced the levels of key proteins involved in leukemia cell survival, including Bcr-Abl and Mcl-1.
Approved Use for Resistant and Intolerant CML
Omacetaxine mepesuccinate's approval was a milestone for patients with CML who had limited options after failing multiple TKI treatments. Clinical trial data showed its efficacy in this treatment-resistant population. The drug provided a new approach for CML management, distinct from the prevailing TKI therapies.
The FDA indication allowed for its use in two specific CML phases:
- Chronic Phase: For adults who were resistant to or intolerant of at least two TKIs.
- Accelerated Phase: Also indicated for adults with disease progression in the accelerated phase who showed resistance or intolerance to prior TKIs.
Administration
Omacetaxine mepesuccinate was administered via subcutaneous injection. The treatment was typically structured in cycles, with varying schedules depending on whether the patient was in an induction or maintenance phase of treatment.
For eligible patients, the drug could be prepared and administered at home with appropriate training from a healthcare provider.
Comparative Look at CML Treatments
To understand omacetaxine mepesuccinate's place in CML therapy, a comparison with Tyrosine Kinase Inhibitors (TKIs) is helpful:
| Feature | Omacetaxine Mepesuccinate (Synribo) | Tyrosine Kinase Inhibitors (e.g., Imatinib) |
|---|---|---|
| Mechanism of Action | Inhibits protein synthesis by binding to the ribosomal A-site, preventing protein elongation. | Directly inhibits the BCR-ABL tyrosine kinase enzyme, blocking its activity. |
| Target | Not a kinase inhibitor. It prevents the synthesis of the BCR-ABL protein and other survival proteins. | The BCR-ABL enzyme itself. |
| T315I Mutation | Effective against the T315I mutation, which confers resistance to many TKIs. | Most first- and second-generation TKIs are ineffective against this mutation. |
| Administration | Subcutaneous injection. | Oral medication (e.g., tablets or capsules). |
| Purpose | Used in later lines of therapy for patients with resistance or intolerance to TKIs. | Often used as first-line or subsequent therapy for CML. |
| Toxicity Profile | Common side effects include myelosuppression, injection site reactions, and GI issues. | Distinct side effect profile, which can also include myelosuppression and fluid retention. |
Adverse Effects and Safety Information
Like all potent oncology medications, omacetaxine mepesuccinate was associated with several adverse effects. The most common were hematological, including severe myelosuppression:
- Thrombocytopenia (low platelets)
- Neutropenia (low neutrophils)
- Anemia (low red blood cells)
Patients experiencing low blood counts were at an increased risk of infections and bleeding. Other common side effects included:
- Diarrhea, nausea, and other gastrointestinal disturbances
- Fatigue and weakness (asthenia)
- Fever (pyrexia)
- Injection site reactions
Serious adverse events were also reported, such as fatal cerebral hemorrhage (linked to severe thrombocytopenia) and severe hyperglycemia. Patients were closely monitored with frequent blood tests to manage these risks.
The Discontinuation of Synribo
Despite its unique mechanism and role in treating resistant CML, omacetaxine mepesuccinate (Synribo) was permanently discontinued by the manufacturer, Teva Pharmaceuticals. The decision was attributed to manufacturing issues and has removed this treatment option from the market. As of mid-2025, Synribo was no longer commercially available, and treatment guidelines for resistant CML have continued to evolve with other available therapies.
Conclusion
In conclusion, the generic name for Synribo is omacetaxine mepesuccinate, a former but distinct treatment for chronic myeloid leukemia. As a protein synthesis inhibitor, it offered a valuable alternative for patients who had failed or could not tolerate standard tyrosine kinase inhibitors, especially those with the T315I mutation. However, due to its permanent discontinuation from the market, it is no longer a viable therapeutic option. Its history highlights the ongoing research and development required to address drug resistance in cancer and the complex landscape of oncology medication supply. For patients previously on or considering this treatment pathway, consultation with an oncologist is essential to explore current therapeutic alternatives.
