How Gene therapy is changing the Beta-thalassemia Treatment outlook?

Beta thalassemia, globally affects almost 288,000 people, with an incidence of 60,000 cases every year. A rare monogenic genetic disease, beta-thalassemia is caused by more than 200 mutations of the beta-globin gene (HBB).

The Beta-thalassemia pharmacological treatment mainly comprises of regular blood-transfusion therapy. The blood transfusion mainly helps in suppressing the enlargement of erythroid. However, many times they cause a gradual accumulation of iron due to insufficient excretory function. Since the body is incapable to get rid of excess iron, thus iron binders (chelators) are used.

Iron chelation therapies

Some of the iron chelation therapies that used are Deferoxamine (DFO), Deferiprone (DFP) and Deferasirox (DFX).

Desferal (deferoxamine mesylate USP), a therapy of Novartis, is indicated for acute iron intoxication treatment and chronic iron overload treatment. Desferal is capable of improving iron excretion in patients with secondary iron overload from multiple transfusions (as may occur in the treatment of some chronic anaemia, including thalassemia). The therapy can be administered via intramuscular, subcutaneous, and intravenous means.

Exjade (Deferasirox), which is again a Novartis product, reduces iron overload in the patient pool of beta-thalassemia and chronic anaemia. The drug is administered once-daily orally.

Ferriprox (deferiprone), a therapy developed by Apotex, like others mentioned above, is an iron-chelator for transfusional iron overload due to thalassemia syndromes.  It is administered thrice a day orally.

Improved diagnostics methodologies, increasing awareness and improved healthcare spending by the governments of different regions will prove to be beneficial in changing the beta-thalassemia course in a positive manner.

Gene Therapy in Beta-thalassemia

The emergence of gene therapy to treat disorders from the root will considerably improve the lives of the patients. Companies like Novartis AG, UniQure N.V. Spark Therapeutics LLC; Bluebird Bio; Kite Pharmaceuticals, Acceleron Pharma Gilead Sciences, Inc. and many others are successfully involved in advancing the Beta-thalassemia market with vast pipeline products.

Gene therapy has the potential to change the beta-thalassemia treatment landscape. Gene therapy in Beta-thalassemia market is expected to influence the US and EU markets more with the adoption of a more technologically advanced healthcare system and quality one-time lifetime treatment.

With Gene therapy, need for monthly blood transfusion stops.

Recently BlueBird Bio has received the approval from the US FDA for its lentiviral vector, LentiGlobin BB305 (zynteglo) is one-time gene therapy. It was granted Breakthrough Therapy designation by the US FDA in 2015. Recently, it has received conditional marketing authorization valid pan-Europe. The company started Phase III trials in 2017 to evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 drug products. The trials are expected to end by 2021.

Acceleron is developing a novel approach Luspatercept or ACE-536, which promises to repair red blood cells (RBC) and increase the RBC count. The therapy is a first-in-class erythroid maturation agent (EMA) being developed to treat patients who have serious blood disorders marked by a late-stage defect in the maturation of red blood cells. Acceleron along with Celgene Corporation are now jointly working to develop and commercialize the therapy to treat anaemia. The US FDA, in 2019, accepted Celgene’s Biologics License Application (BLA) for the therapy. The company is now running the Phase III trials for Luspatercept expected to complete by 2025.

The collaboration is working in another drug Sotatercept or ACE-011, which is a biologic drug. The drug boasts of increasing haemoglobin and red blood cells level. It is a first-in-class, novel bone-forming compound. The FDA granted orphan status for the use of Sotatercept to treat patients with beta-thalassemia in 2013. It is currently in Phase II clinical trial, expected to complete in 2020.

Need for novel treatment approach, and a vast pipeline are acting as fuel in driving the Beta-thalassemia market ahead along with the added competition due to an increasing interest of major pharma players.