dm+d

37761711000001107

Refrigerated Storage

Cablivi Sanofi

Sanofi
Cablivi
Powder and solvent for solution for injection

In the event of an inadvertent temperature excursion the following data may be used:

Cablivi may be stored at a temperature <25°C for a single period of up to 2 months, but not beyond the expiry date. After exposure to room temperature, store Cablivi outside of the fridge.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

12 November 2021
London MI Service

New Medicines

CabliviAcquired thrombotic thrombocytopenic purpura (aTTP)

Information

Cablivi
New molecular entity
Sanofi Genzyme
Sanofi Genzyme

Development and Regulatory status

Launched
Launched
Approved (Licensed)
February 2020
Yes
Yes
Jun 20Licence change approved in EU [23].
Apr 20CHMP issues a positive opinion for an extension to the existing indication to include treatment of adolescents. The new indication will be treatment of adults and adolescents of 12 years of age and older weighing at least 40 kg experiencing an episode of acquired thrombotic thrombocytopenic purpura (aTTP), in conjunction with plasma exchange and immunosuppression [22].
Feb 20Launched in the UK. Price 1 pack=£4143.00 [21]
Feb 19Approved in US [18].
Jan 19Sanofi does plan to launch Cablivi in the UK but launch plans unclear. Cablivi has been selected for NICE technology appraisal so launch may be delayed until the outcome of this is known [17].
Oct 18Has been filed in US [15].
Oct 18Launched in Germany by Sanofi-Genzyme [19]
Sep 18Approved in the EU. Caplacizumab (Cablivi) is the first therapeutic specifically indicated for the treatment of aTTP. Also filed in the US with priority review designation with a target action date Feb 2019 [12].
Sep 18US filing planned for acquired TTP [14].
Jun 18Recommended for EU approval by CHMP - the full indication is "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 caplacizumab be prescribed and supervised by physicians experienced in the treatment of management of patients with thrombotic microangiopathies [11].
Jan 18CHMP extends earlier clock-stop from June 17 related to Day 120 List of Questions, as the company still wished for time to respond to outstanding issues [10].
Jul 17Awarded Fast Track Designation by US FDA [7].
Jan 17Ablynx have submitted a Marketing Authorisation Application (MAA) to the EMA for caplacizumab, its first-in-class anti-von Willebrand factor (vWF) Nanobody® for acquired thrombotic thrombocytopenic purpura [5].
May 15Ablynx reported that it intends to seek conditional approval from the EMA for caplacizumab in the treatment of acquired thrombotic thrombocytopenic purpura in the first half of 2017; product launch is anticipated in 2018 [3].

Category

A bivalent anti-von Willebrand Factor humanised nanobody. It inhibits interactions between von Willebrand factor, collagen and platelets to prevent the earliest stages of thrombus formation.
TTP has an annual incidence of 6 cases per million in the UK [1].
Acquired thrombotic thrombocytopenic purpura (aTTP)
Intravenous

Further information

Yes

Trial or other data

Jan 19Results of PIII HERCULES study (NCT02553317) published in the NEJM. The trial (n=145) found median time to normalisation of the platelet count was marginally shorter with caplacizumab (10mg IV bolus then 10mg daily subcutaneously given during plasma exchange and for 30 days after) than with placebo (2.69 vs. 2.88 days, p=0.01) [16].
Sep 18Currently commissioned by CCGs. Transfer from CCG to NHS England in progress, due by 2019 [13].
Jan 18Sanofi has agreed to buy Ablynx, the proposed deal having been approved by the Directors of both companies [8].
Oct 17Ablynx announce positive topline results from the Phase III HERCULES (NCT02553317) study. Treatment with caplacizumab plus standard-of-care resulted in reduction in time to platelet count response (p<0.01), meeting the primary endpoint of the study and a measure of prevention of further microvascular thrombosis. Two key secondary endpoints were also met; reduction in % of pts with aTTP-related death, recurrence of aTTP or at least one major thromboembolic event during study drug treatment (p<0.0001), with recurrences being the driver for achievement of this endpoint. The proportion of pts with a recurrence of aTTP in the overall study period (inc a 28 day follow-up after discontinuation of study drug treatment) was lower in the caplacizumab arm vs. placebo (p<0.001). The frequency and severity of treatment related adverse effects were similar between groups but serious adverse effects were more common with placebo as they were related to a recurrence of aTTP. The % of pts with bleeding-related adverse effects was higher in the caplacizumab group vs. placebo (66.2% vs. 49.3%) but most were mild or moderate in severity [8].
Feb 16Results of TITAN (NCT01151423) published in the New England Journal of Medicine. This RCT (n=75) found caplacizumab induced faster resolution of acute episodes of thrombotic thrombocytopenic purpura (39% reduction in time to response, p=0.005) vs. placebo, but it did not have effect on risk of relapse. Bleeding-events were more common with caplacizumab [4].
Sep 15PIII HERCULES study (NCT02553317) to evaluate efficacy and safety of caplacizumab treatment in more rapidly curtailing ongoing microvascular thrombosis when administered in addition to standard of care treatment in subjects with an acute episode of acquired TTP begins. 92 patients will be recruited in the US and Belgium. Primary outcome is time to platelet count response; collection of data is expected to complete in Oct 17 [2].

Evidence based evaluations