Breakthrough Clinical Results
CRISPR Therapeutics and Sirius Therapeutics announced a multi-target collaboration to co-develop and co-commercialize SRSD107, a long-acting siRNA therapy targeting Factor XI for thromboembolic disorders. SRSD107 showed significant reductions in FXI activity and increased aPTT in Phase 1 trials, with effects lasting up to 6 months. CRISPR will pay $25 million upfront and $70 million in equity to Sirius. The collaboration expands CRISPR's therapeutic portfolio beyond gene editing, focusing on a significant unmet need in patients at risk of life-threatening thromboembolic events.
Key Highlights
- Strategic partnership between CRISPR Therapeutics and Sirius Therapeutics to develop and commercialize siRNA therapies.
- SRSD107, a long-acting siRNA targeting Factor XI, demonstrated sustained efficacy for up to 6 months in Phase 1 trials.
- CRISPR Therapeutics will make an upfront payment of $25 million in cash and $70 million in equity to Sirius Therapeutics.
- Collaboration expands CRISPR's therapeutic toolkit beyond gene editing to include siRNA therapies.
Incidence and Prevalence
The provided medical articles do not contain the latest global incidence and prevalence estimates for all thromboembolic disorders as a single category. The articles focus on specific thromboembolic conditions or broader disease categories, and often present data for specific regions or countries rather than global figures. However, some relevant information on specific thromboembolic conditions can be extracted:
Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT): While not explicitly stated, these conditions are often studied together as venous thromboembolism (VTE). One study on pulmonary hypertension (PH) mentions thromboembolic disease as a contributing factor, but doesn't provide specific VTE incidence or prevalence. Another study on chronic thromboembolic pulmonary hypertension (CTEPH) discusses the challenges in diagnosing this specific type of PH, highlighting the lack of clear epidemiological data, particularly in China.
Chronic Thromboembolic Pulmonary Hypertension (CTEPH): This specific type of PH, caused by unresolved blood clots in the lungs, lacks comprehensive epidemiological data. One article mentions the need for more research on CTEPH epidemiology in China due to high rates of misdiagnosis and missed diagnosis.
Polycythemia Vera (PV): A German study from 2021 estimated the prevalence of PV at 28.6 per 100,000 and incidence at 3.3 per 100,000 in the adult population. PV is a blood cancer that can increase the risk of thromboembolic events.
Pulmonary Arterial Hypertension (PAH): A study from the Global Burden of Disease Study examined PAH, a specific type of PH. Reported prevalence ranged from 0.37 cases/100,000 persons in French children to 15 cases/100,000 persons in an Australian study. Reported incidence ranged from 0.008 cases/100,000 person-years in Finland to 1.4 cases/100,000 person-years in a US study. PAH can lead to thrombotic complications.
General Observations:
- Data Variability: The available data on thromboembolic conditions varies significantly due to differences in study design, diagnostic criteria, and populations studied. This makes direct comparisons and global estimations challenging.
- Need for Harmonization: Several articles emphasize the need for standardized methods and data collection for thromboembolic disorders to improve surveillance and understanding of the global burden.
- Focus on Specific Conditions: The research tends to focus on specific conditions like CTEPH or PAH rather than all thromboembolic disorders as a whole.
In summary, the provided texts do not offer the latest global incidence and prevalence data for all thromboembolic disorders collectively. More research and standardized data collection are needed to accurately assess the global burden of these conditions.
Risk Factors and Comorbidities
Thromboembolic disorders, encompassing conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE), arise from a complex interplay of risk factors and comorbidities. Pinpointing the top 3 is challenging due to variations across studies and populations, but some consistently emerge as prominent contributors.
-
Active Cancer: Cancer significantly increases VTE risk, with incidence varying by cancer type. Pancreatic, liver, and non-small cell lung cancers show the highest incidence (>70 per 1000 person-years), while breast, melanoma, and prostate cancers have lower rates (<20 per 1000 person-years). The prothrombotic state in cancer is attributed to tumor-derived procoagulants, inflammatory cytokines, and interactions with the coagulation system.
-
Prior VTE: A history of VTE is a strong predictor of recurrence. The 10-year recurrence risk ranges from 30% to 50%, higher in patients with primary DVT than PE. Residual vein thrombosis and elevated D-dimer levels further increase the risk. The underlying mechanisms likely involve persistent vascular damage and ongoing activation of the coagulation system.
-
Hospitalization/Immobilization: Hospital-associated VTE (HA-VTE) is a well-known complication, with incidence around 1.2% of medical admissions. Reduced mobility during hospitalization, surgery, or prolonged illness contributes significantly to VTE risk. Immobilization promotes venous stasis, a key component of Virchow's triad (venous stasis, endothelial injury, and hypercoagulability), which describes the pathogenesis of thrombosis.
Beyond these top 3, several other factors and comorbidities consistently increase VTE risk:
- Age: Advanced age is a major risk factor, with VTE incidence increasing substantially in older individuals.
- Obesity: Obesity is linked to increased inflammation, impaired fibrinolysis, and venous stasis, all contributing to VTE risk.
- Surgery: Major surgery, especially orthopedic and cancer surgery, significantly elevates VTE risk due to tissue trauma, inflammation, and immobilization.
- Trauma and Fractures: Similar to surgery, trauma and fractures increase VTE risk through tissue damage, inflammation, and immobilization.
- Inherited Thrombophilia: Genetic conditions like Factor V Leiden and Prothrombin G20210A mutation increase the risk of thrombosis.
- Oral Contraceptives and Hormone Replacement Therapy: Estrogen-containing medications can enhance coagulation and increase VTE risk.
- Pregnancy and Puerperium: Pregnancy induces a hypercoagulable state to prevent postpartum hemorrhage, but this also increases VTE risk.
- Medical Conditions: Certain medical conditions like heart failure, diabetes, and antiphospholipid syndrome are associated with increased VTE risk.
It's crucial to consider the interplay of these risk factors and comorbidities when assessing an individual's VTE risk. The presence of multiple risk factors can synergistically increase the overall risk, necessitating appropriate preventive measures.
Drug used in other indications
SRSD107 is currently being investigated for the following indications in clinical trials:
- Thrombosis: This includes both arterial and venous thrombosis.
- Venous Thrombosis: Specifically targeting venous thromboembolism (VTE).
- Thromboembolic Disorders: This encompasses a broader range of conditions related to blood clot formation, including myocardial infarction, ischemic stroke, and VTE.
- Arterial thrombosis
The intervention models for these trials are primarily:
- Randomized: Participants are randomly assigned to different treatment groups (e.g., SRSD107 vs. placebo).
- Double-blind: Both participants and researchers are unaware of the treatment assignment.
- Placebo-controlled: A control group receives a placebo to compare the effects of SRSD107 against a non-active treatment.
- Single ascending dose: Different groups of participants receive increasing doses of SRSD107 to evaluate safety and tolerability.
- Multiple ascending dose: Participants receive multiple doses of SRSD107 to assess the long-term effects and optimal dosing regimen.
- Parallel Assignment: Different treatment groups run concurrently.
- Quadruple Blind: Four parties involved in the trial are blinded to the treatment assignment.
One trial specifically mentions a Phase 2 study for the prevention of VTE in patients undergoing total knee arthroplasty. This trial aims to confirm the anticoagulant benefits of SRSD107 and inform dose selection for future pivotal trials.
It's important to note that while SRSD107 is primarily being investigated for thromboembolic disorders, its mechanism of action (inhibiting Factor XI) may have broader applications in other conditions related to blood clotting. Further research and clinical trials will be needed to explore these possibilities.