Revcovi for the Treatment of ADA-SCID

Revcovi (elapegademase-lvlr) is a PEGylated recombinant adenosine deaminase (rADA) enzyme indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in paediatric and adult patients.

Developed by Leadiant Biosciences, the drug will replace Adagen, which was approved in 1990 and is the main enzyme replacement therapy (ERT) available for ADA-SCID in the US.

A biologics license application (BLA) for Revcovi was submitted to the US Food and Drug Administration (FDA) in October 2017. The FDA approved the drug under Fast Track and priority review in October 2018.

The drug has also received orphan drug designation from the FDA.

ADA-SCID disease details

ADA-SCID is a rare inherited genetic disorder caused due to a mutation of the adenosine deaminase (ADA) gene, which is responsible for the production of the ADA enzyme. The enzyme is responsible for deamination of adenosine and deoxyadenosine, which are harmful to white blood cells.

Improper functioning of the ADA enzyme results in both intracellular and extracellular accumulation of adenosine and deoxyadenosine to toxic levels, which leads to the death of T-cells and B-cells.

Commonly known as Bubble Boy Disease, the condition leads to severe and recurrent infections, T-lymphopenia, impaired immune functioning and metabolic abnormalities. It is also responsible for severe combined immunodeficiency (SCID) in paediatric patients and is known to affect approximately one in 200,000 newborns globally.

Unless diagnosed within the first few months, patients affected with ADA-SCID mostly fail to live beyond the age of two years.

Revcovi’s mechanism of action

Revcovi provides an external source of the ADA enzyme, which breaks down the plasma adenosine rapidly and causes outward movement of accumulated intracellular adenosine into the plasma. This increases the number of lymphocytes in the blood.

The drug is available as a sterile, preservative-free and colourless solution in a single-dose vial for intramuscular administration.

Clinical trials on Revcovi

The US FDA approved Revcovi based on the efficacy and safety data from two Phase III clinical trials named Study 1 (STP-2279-002) and Study 2 (STM-279-301).

The trials were conducted in the US and Japan respectively, enrolling ten patients suffering from ADA-SCID that were aged between eight and 37 years. Of the participants, six were male and four were female. The primary endpoints of the studies were changes in trough plasma ADA activity, trough erythrocyte dAdo nucleotides (dAXP) levels and immune function.

Study 1 was an open-label, multi-centre, single-arm, crossover study that enrolled six patients. Participants were administered with a weekly dose of 0.188mg/kg to 0.292mg/kg for two to 146 weeks. After 21 weeks, patients treated with Revcovi showed improved ADA enzyme activity and increased total lymphocyte count.

Study 2 was an open-label, multi-centre, single-arm study that enrolled four patients. Participants were administered with a dose ranging from 0.1mg/kg-0.13mg/kg. Improved serum ADA activity was observed in all four patients after 21 weeks.

The most common side effects observed in the studies were coughing, respiratory infections and vomiting.

Marketing commentary on Leadiant Biosciences

Leadiant Biosciences is a research-oriented pharmaceutical company headquartered in Italy. In Europe, the company operates under its former name Sigma-Tau Pharmaceuticals.

Leadiant is focused on developing therapies to help patients with rare and ultra-rare diseases. The company’s approved products are Revcovi, Chenodeoxycholic acid Leadiant, Natulan, Abelcet, Adagen, Carnitor, Carnitor, Cystaran, DepoCyt and Matulane.

Revcovi will replace the company’s existing enzyme replacement therapy Adagen, which is obtained from animal sources. The production process for Adagen is cumbersome and needs to follow stringent FDA regulations leading to cost inefficiencies.

Developed using recombinant technology, Revcovi will eliminate the need for sourcing from animals and improve efficiencies for the company.