Date: 2018-09-03
Type of information: Granting of a Market Authorisation in the EU
Product name: Cablivi®
Compound: caplacizumab
Therapeutic area: Autoimmune diseases - Rare diseases
Action mechanism:
- nanobody. Caplacizumab is a bivalent anti-von Willebrand Factor (vWF) Nanobody. vWF is implicated in thrombotic thrombocytopenic purpura (TTP), a rare disease where pre-cursors of vWF (ultra-large vWF multimers; UL-vWF) are present in the blood of patients and lead to blood clot formation and potentially life-threatening pathology. Caplacizumab inhibits platelet binding to UL-vWF and thus has the potential to prevent the formation of these string-like clots in the blood of patients with acquired TTP. Caplacizumab received orphan drug designation in the US and EU in 2009 and could be the first drug specifically approved for the treatment of acquired TTP as an adjunct to plasma exchange.
- Caplacizumab was developed by Ablynx and Sanofi has acquired the Belgian biotech in January 2018.
Company: Ablynx (Belgium), now Sanofi (France)
Disease: acquired thrombotic thrombocytopenic purpura (aTTP)
Latest news:
- • On September 3, 2018, The European Commission has granted marketing authorization for Cablivi™ (caplacizumab) for the treatment of adults experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP). Cablivi is the first therapeutic specifically indicated for the treatment of aTTP. Sanofi Genzyme, the specialty care
global business unit of Sanofi, will work with relevant local authorities to make Cablivi™ available to patients in need in countries across Europe. Cablivi™ is the company’s first Nanobody®-based medicine to receive approval and the first newly approved product that will be part of Sanofi Genzyme’s Rare Blood Disorders
franchise.
- The approval of Cablivi™ in the EU is based on the Phase II TITAN and Phase III HERCULES studies in 220 adult patients with aTTP. The efficacy and safety of caplacizumab in addition to standard-of-care treatment, daily PEX and
immunosuppression, were demonstrated in these studies.
In the HERCULES study, treatment with caplacizumab in addition to standard-of-care resulted in a significantly shorter time to platelet count response (p<0.01), the study’s primary endpoint; a significant reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event during study drug treatment (p<0.0001); and a
significantly lower number of aTTP recurrences in the overall study period (p<0.001). Importantly, treatment with caplacizumab resulted in a clinically meaningful reduction in
the use of PEX and length of stay in the intensive care unit (ICU) and the hospital, compared to the placebo group.
- In clinical trials, caplacizumab demonstrated a safety profile, consistent with its mechanism of action. The most frequently reported adverse reactions were epistaxis, headache and gingival bleeding. No deaths were reported during study drug treatment in the caplacizumab group in the TITAN and HERCULES studies, while for the placebo group, two deaths were reported in the TITAN study and three deaths in the HERCULES study.
- Additionally, the FDA has accepted for priority review the Biologics License Application for caplacizumab for treatment of patients 18 years of age and older experiencing an episode of aTTP. The target action date for the FDA decision is February 6, 2019.
- • On June 28, 2018 , the Committee for Medicinal Products for Human Use (CHMP) adopted a positive
opinion, recommending the granting of a marketing authorisation for Cablivi® (caplacizumab) intended for the treatment of acquired thrombotic thrombocytopenic purpura. The drug will be available as a 10 mg powder and solvent for solution for injection. The benefits with Cablivi® are its ability to reduce time to platelet count response, the recurrence rate of the disease, the number of days of plasma exchange, the volume of plasma used, and the length of hospitalization and intensive care unit stay.
- The most common side effects are bleedings. Other most
common adverse reactions were pyrexia, fatigue, headache, urticaria, injection site reaction, myalgia, injection site pruritus, injection site erythema, cerebral infarction, dyspnoea.
- The full indication is: "Cablivi® is indicated for the treatment of adults experiencing an episode of acquired
thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression."
It is proposed that Cablivi be prescribed and supervised by physicians experienced in the treatment of management of patients with thrombotic microangiopathies.
- • On July 26, 2017 , Ablynx announced that the FDA has granted Fast Track designation for caplacizumab, a first-in-class anti-von Willebrand factor (vWF) Nanobody® being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). The potential of caplacizumab has been demonstrated in the Phase II TITAN study which supports the Marketing Authorisation Application (MAA) submitted to the European Medicines Agency (EMA) in February 2017. Caplacizumab is currently being further evaluated in the randomised, double-blind, placebo-controlled Phase III HERCULES study. Results from this Phase III study will be reported in the second half of 2017 and are expected to further support the MAA, as well as a planned BLA filing in the
United States in 2018.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2018-09-03
Favourable opinion UE: 2018-06-28
Favourable opinion USA:
Orphan status USA: 2009-04-14
Orphan status UE: 2009-04-30
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
