Novel nanobody therapy transforms treatment and survival of patients with life-threatening blood clots due to rare immune disorder
UCLH clinical trials have proven that a new nanobody therapy, Caplacizumab, can shorten treatment of the life-threatening blood clotting disease; Immune Thrombotic Thrombocytopenic Purpura (iTTP), from weeks to days and improves patient survival. UCLH data contributed to Caplacizumab’s approval for NHS use and it is now standard-of-care for iTTP worldwide.
iTTP is a rare immune disorder in which blood clots form in the heart, brain and kidneys. It is caused by the immune system erroneously producing antibodies that destroy an enzyme within the body called ADAMTS 13 that is needed to prevent platelets (blood clotting proteins) sticking together to form clots1. Standard treatment exchanges the patient’s blood plasma for healthy plasma from a donor, replacing the missing enzyme, and immunosuppressive drugs to prevent production of the ADAMTS 13-destroying antibodies.
Prof Scully and colleagues at UCLH carried out phase II and III studies of a new therapy for iTTP, Caplacizumab, a ‘nanobody’ therapy that binds to specific protein regions to prevent platelets from sticking together. The TITAN and HERCULES trials showed that Caplacizumab normalised platelet levels in three days, compared with 20 days with placebo. Caplacizumab-treated patients needed 30% fewer plasma exchanges and less time in intensive care, had shorter hospital stays and all survived (compared with three deaths in the placebo group)2.
Following these results UK regulators allowed compassionate use of Caplacizumab therapy at UCLH, prior to full approval. UCLH established a network to give patients access to the therapy nationally collect data. This generated real-world evidence that contributed to the NICE recommendation to recommend Caplacizumab to treat iTTP in the NHS3.
Now the standard of care for iTTP worldwide, Caplacizumab has transformed care of hospitalised patients, improving survival and raising platelet counts so quickly that patients no longer need a central line (a tube inserted into a major vein over several weeks to allow for regular intravenous drug treatment), the worst part of iTTP treatment according to patients.
UCLH is now trialling a genetically engineered version of the ADAMTS 13 enzyme that avoids the need for plasma exchange. Treatment is with a 10ml infusion that takes 5-10 minutes, which could replace the current treatment of exchanging 3 to 5 litres of blood plasma over several hours.
References
1 Alwan, Blood. 2017
2 Scully, NEJM 2019
3 Dutt, Blood 2021
