Why Is Saracatinib Not Commercially Available in the USA?
Saracatinib, also known by its code AZD0530, is a potent inhibitor of Src-family and Abl tyrosine kinases. While its pharmacological profile seemed promising, its developmental journey has led it down a path of repurposing rather than immediate commercialization. Its current status as an investigational drug stems from its mixed results in earlier clinical trials.
History of Saracatinib in Oncology
Saracatinib was initially developed by AstraZeneca for the treatment of various cancers, where Src-kinase activity is often implicated in tumor progression and proliferation.
- Promising Preclinical Data: Early animal studies showed promising anti-tumor effects, and Phase I clinical trials in humans demonstrated tolerability at certain doses.
- Limited Phase II Efficacy: Despite the early promise, Phase II trials in a wide range of cancers—including breast, lung, and prostate cancer—yielded disappointing results. Many patients experienced disease progression, and the therapeutic benefit was not deemed significant enough to warrant further development for those indications.
- Elevated Adverse Effects: Clinical trials in oncology also noted a high rate of adverse effects, contributing to the decision to cease its development for most cancer therapies.
Following these results, AstraZeneca discontinued its pursuit of saracatinib for additional oncology indications, effectively ending its path to commercial approval for cancer treatment.
The Repurposing of Saracatinib
With its initial oncology development halted, saracatinib became a candidate for drug repurposing—the process of investigating an existing drug for new therapeutic uses. The scientific community has since explored its potential for diseases outside of cancer.
Focus on Idiopathic Pulmonary Fibrosis (IPF)
One of the most promising new applications for saracatinib has emerged in the field of pulmonary health. Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive lung disease characterized by the scarring of lung tissue.
- Computational Discovery: A computational screening approach identified saracatinib as a potential candidate for IPF treatment. This method compared the drug's gene expression signature with that of IPF to find a strong inverse correlation, suggesting it could reverse fibrotic activity.
- Preclinical Success: In preclinical studies, saracatinib demonstrated antifibrotic effects that were as good as or better than the currently approved drugs for IPF, nintedanib and pirfenidone. It showed promise in blocking fibrogenic responses in human lung fibroblasts and mouse models.
- Orphan Drug Designation: The FDA granted saracatinib Orphan Drug Designation (ODD) for IPF in 2019. This designation encourages the development of treatments for rare diseases, but it does not equate to marketing approval.
- Clinical Trials: As a result of these findings, clinical trials, such as the Phase 1b/2a STOP-IPF trial (NCT04598919), were initiated in the USA to evaluate saracatinib's safety and efficacy in IPF patients. These trials are the primary means of accessing the drug for American patients.
Other Investigational Uses
Saracatinib is also being investigated for other conditions that involve similar kinase pathways.
- Alzheimer's Disease: The drug has shown potential in targeting a specific protein kinase (Fyn) associated with Alzheimer's disease pathology. Phase I and Phase II trials were conducted to assess its safety and ability to cross the blood-brain barrier.
- Fibrodysplasia Ossificans Progressiva (FOP): Preclinical research identified saracatinib as a potent inhibitor of the ALK2 kinase, which is mutated in patients with FOP, a rare genetic disorder causing extra-skeletal bone formation. The STOPFOP trial, based in Europe, is investigating its use for this indication.
How Saracatinib Is Currently Accessed in the USA
Since saracatinib is not commercially available, access is strictly controlled. For individuals in the USA, there are generally two pathways to access an investigational drug, though neither is guaranteed or widespread.
Access through a Clinical Trial
This is the most common way to receive saracatinib. Eligible patients can enroll in a clinical trial where the drug is being studied. Access is determined by strict inclusion and exclusion criteria.
- Ongoing Studies: Patients interested in saracatinib for IPF, for example, would need to enroll in a study like the STOP-IPF trial.
- Limited Slots: Clinical trials have a limited number of participants and may not be recruiting at all times.
Access via Expanded Access (Compassionate Use)
In some cases, the FDA allows for expanded access for a patient with a serious disease who cannot participate in a clinical trial. This is an option of last resort and requires approval from both the FDA and the drug manufacturer.
Comparison of Saracatinib (Investigational) vs. Approved IPF Drugs
This table highlights the difference in status and access between saracatinib and the two FDA-approved drugs for Idiopathic Pulmonary Fibrosis, nintedanib and pirfenidone.
| Feature | Saracatinib (Investigational) | Nintedanib (Approved) | Pirfenidone (Approved) |
|---|---|---|---|
| FDA Approval Status | Not approved for marketing in the USA. | Approved for IPF. | Approved for IPF. |
| Availability | Restricted to clinical trials or expanded access programs. | Commercially available by prescription. | Commercially available by prescription. |
| Primary Indication | Under investigation for repurposing; initially for oncology. | Idiopathic Pulmonary Fibrosis. | Idiopathic Pulmonary Fibrosis. |
| Mechanism of Action | Inhibitor of Src-family and Abl kinases. | Tyrosine kinase inhibitor targeting multiple pathways. | Mechanism not fully understood, but has antifibrotic effects. |
| Access Method | Enrollment in an ongoing clinical trial (e.g., STOP-IPF). | Prescribed by a physician. | Prescribed by a physician. |
| Potential Efficacy | Preclinical studies suggest equal or superior efficacy to approved drugs in some models, but unproven clinically. | Demonstrated efficacy in slowing disease progression. | Demonstrated efficacy in slowing disease progression. |
Conclusion
In summary, despite its initial promise in cancer therapy and encouraging preclinical data for repurposed uses like IPF, saracatinib is not available in the USA for commercial use. The drug's journey highlights the rigorous and often uncertain process of drug development and repurposing. Its access is currently limited to structured clinical research settings, providing a pathway for eligible patients to receive the drug while its safety and efficacy are further evaluated. Individuals should consult with their healthcare providers to discuss treatment options and eligibility for clinical trials involving investigational drugs such as saracatinib.
Current Status of Saracatinib Research in the USA
For those following its development, the repurposing of saracatinib from a failed oncology drug to a potential therapy for IPF and other diseases is a key area of interest. Research continues to define its potential therapeutic role, particularly in IPF, where it has received Orphan Drug Designation. Its path forward depends on the outcome of ongoing and future clinical trials, which will determine if it ever gains marketing approval from the FDA for a new indication. The shift in its focus from oncology to other therapeutic areas, such as fibrotic and neurological disorders, demonstrates the adaptability of drug development in response to clinical data and new scientific insights.
