Revcovi™ – Leadiant Biosciences Inc. FDA approval for treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID)

New Drug Overview – elapegademase-lvlr (Revcovi™)

On October 5, 2018, the U.S. Food and Drug Administration (FDA) approved elapegademase-lvlr (Revcovi™) for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.  (ADA-SCID) is a rare genetic disorder that primarily affects infants and young children and is fatal if left untreated.  The FDA previously granted orphan drug status to Revcovi™.  According to the manufacturer, Revcovi™ is a recombinant adenosine deaminase (rADA) enzyme which eliminates the need to source the enzyme from animals. It works by supplementing levels of an essential enzyme, adenosine deaminase (ADA).

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
elapegademase-lvlr Revcovi ™ Leadiant Biosciences Inc. October 5, 2018 n/a n/a
Labeled Indication:
Treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients
Drug Class Comparative Drugs in Class Route of Administration Dosing Schedule
enzyme replacement therapy (ERT) Adagen® Intramuscular 0.2 mg/kg twice a week or weekly depending on previous treatments
Mechanism of Action:
Provides an exogenous source of ADA enzyme that is associated with a decrease in toxic adenosine and deoxyadenosine nucleotides levels as well as an increase in lymphocyte number
Clinical Trial Summary (Efficacy):
The approval is based on results from two multicenter, open-label clinical trials which demonstrate that Revcovi™ increases ADA activity, reduces concentrations of toxic metabolites that are the hallmark of ADA-SCID and improves total lymphocyte counts.

 Study 1 (NCT 01420627): ongoing Phase 3, open-label, multicenter, single-arm, one-way crossover study (results based on 6 patients)

Study Dose: The starting weekly dose of REVCOVI was calculated based on the last Adagen dose received in the study. Weekly REVCOVI doses ranged from 0.188 mg/kg to 0.292 mg/kg.

Primary Outcome Measurements:

·         Trough dAXP Level (metabolic detoxification was defined as a trough erythrocyte dAXP concentration equal to or below 0.02 mmol/L)

·         Trough plasma ADA activity (adequate trough plasma ADA activity is defined as trough plasma ADA activity equal to or above 15 mmol/hr/L)

·         Immune status (lymphocyte and B-, T-, and NK-lymphocyte subset counts as well as quantitative immunoglobulin [Ig] concentration [IgG, IgA, IgM])

Study 2 (NCT n/a conducted in Japan): single-arm clinical study that assessed the safety, efficacy and PK of REVCOVI in patients with ADA-SCID (results based on 4 patients)

Study Dose: dosing was customized for each patient based on exposure to previous therapy.

Primary Outcome Measurements:

·         Trough dAXP Level (metabolic detoxification was defined as a trough erythrocyte dAXP concentration equal to or below 0.02 mmol/L)

·         Trough plasma ADA activity (adequate trough plasma ADA activity is defined as trough plasma ADA activity equal to or above 15 mmol/hr/L)

·         Immune status (lymphocyte and B-, T-, and NK-lymphocyte subset counts

Warnings and Adverse Effects (AE):
Warning: Injection Site Bleeding in Patients with Thrombocytopenia: Increased risk of local bleeding in patients with thrombocytopenia; should not be used if thrombocytopenia is severe.

Delay in Improvement of Immune Function: Protect immune deficient patients from infections until improvement in immune function.

AE: The most common adverse reactions reported were cough (50%) and vomiting (33%)
NDC Strength Volume Presentation Storage
57665-0002-01 1.6 mg/ml 1.5 ml Single dose vial Refrigeration
Drug Sales Forecast (in millions):
2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F) 2024(F)
Revcovi TM n/a n/a n/a n/a n/a n/a n/a

 

References:

Business Wire A Berkshire Hathaway Company Press Release https://www.businesswire.com/news/home/20181005005525/en/FDA-Approves-Revcovi%E2%84%A2-New-Enzyme-Replacement-Therapy  Accessed October 15, 2018

Global Data Pharma Intelligence Center https://pharma.globaldata.com Accessed October 15, 2018.

RJ Health Systems Inc Reimbursement Codes https://www.reimbursementcodes.com Accessed October 15, 2018.

U.S. Food and Drug Administration Drugs@FDA: FDA Approved Drug Products Product Labeling https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761092s000lbl.pdf  Accessed October 15, 2018.

 

Additional 2018 Pipeline Reviews are available in our pipeline library.

Please see the September 2018 FDA Actions Newsletter for additional information on recent FDA approvals.