Gamifant® – Novimmune SA FDA approval: Treatment of pediatric, adult patients with primary hemophagocytic lymphohistiocytosis (HLH)

New Drug Overview – emapalumab-lzsg (Gamifant®)

On November 20, 2018, the U.S. Food and Drug Administration (FDA) approved emapalumab-lzsg (Gamifant®) for the treatment of pediatric (newborn and above) and adult patients with primary hemophagocytic lymphohistiocytosis (HLH) who have refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.

Primary HLH is an ultra-rare disease, with rough estimates of new cases in the U.S. at less than 100 per year. It is a progressive disease marked by hyperinflammation, leading to multiple organ failure. Hyperproduction of interferon gamma (IFNy), is thought to drive immune system hyperactivation. Previously there was no FDA approved drug for treatment. The immediate therapeutic goal is to control hyperinflammation in preparation for haematopoietic stem-cell transplant. Current treatment prior to transplant includes steroids and chemotherapy not specifically approved to treat primary HLH. According to Michael Jordan, MD the Primary Investigator in the emapalumab clinical trial, “Emapalumab represents an entirely new approach to treating primary HLH and helping these very sick patients reach haematopoietic stem cell transplant.”1 The FDA granted emapalumab-lzsg Priority Review, Orphan Drug Designation, Breakthrough Therapy Designation and Rare Pediatric Disease Designation.

Generic Name Brand Name Manufacturer Approval Date Anticipated Availability Accelerated Review
emapalumab-lzsg Gamifant® Novimmune SA November 20, 2018 Q1 of 2019 Yes
Labeled Indications
Treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy
Drug Class Comparative Drugs in Class Route of Administration Dosing Schedule
monoclonal antibody (mAb), interferon gamma (IFNγ) blocking antibody None, innovator intravenous 1mg/kg twice per week, with increases based on clinical and laboratory criteria, until haematopoietic stem cell transplant (HSCT)
Mechanism of Action:
Binds to and neutralizes cytokine interferon gamma (IFNγ)
Clinical Trial Summary (Efficacy):
Study Reference Number: NCT01818492

Study: Evaluated in a multicenter, open-label, single-arm trial in 27 pediatric patients with the approved indication. 20 patients completed the study.

Study Dose: Starting dose of 1 mg/kg every 3 days. Subsequent doses could be increased to a maximum of 10 mg/kg based on clinical and laboratory parameters interpreted as unsatisfactory response. Forty-four percent of patients remained at a dose of 1 mg/kg, 30% of patients increased to 3-4 mg/kg and 26% of patients increased to 6-10 mg/kg.

Study Duration: Duration was up to 8 weeks after which patients could continue treatment on the extension study.

Primary Outcome Measurement:

Efficacy measurement was overall response rate (ORR) defined as complete or partial response or HLH improvement using an algorithm including objective clinical and laboratory parameters.  ORR at the end of treatment was 17 of 27 (63%) (95% CI: 0.42, 0.81) (p-value 0.013).

Warnings and Adverse Effects (AE):
Warning(s):

·         Infections: Monitor patients for signs and symptoms and treat promptly. Testing for specific latent infections and administration of specific prophylactic therapy is recommended in the package insert.

·         Live Vaccines: The administration of live or live attenuated vaccines to patients is recommended against.

·         Infusion-Related Reactions: The package insert recommends monitoring patients for infusion-related reactions along with recommended actions.

AE(s):

·         The most common adverse reactions (≥ 20%): infections, hypertension, infusion-related reactions, and pyrexia.

NDC Strength Volume Presentation Storage
72171-0501-01 5 mg/ml 2 ml Single dose vial Refrigerate
72171-0505-01 5 mg/ml 10 ml Single dose vial Refrigerate
Drug Sales Forecast (in millions):
  2018(F) 2019(F) 2020(F) 2021(F) 2022(F) 2023(F) 2024(F)
Gamifant ® 10 29 68 126 170 217

 

References:

Novimmune News 20 November 2018 “FDA approves Gamifant® (emapalumab), the first and only treatment for primary haemophagocytic lymphohistiocytosis (HLH)” https://www.novimmune.com/en/swiss-biopharmaceutical-company/news/2018/fda-approves-gamifantreg-emapalumab-first-and-only-treatment-primary-haemophagocytic-lymphohistiocytosis-hlh.html Accessed November 29, 2018.

Global Data Pharma Intelligence Center https://pharma.globaldata.com Accessed November 29, 2018.

RJ Health Systems Inc Reimbursement Codes https://www.reimbursementcodes.com Accessed November 29, 2018.

U.S. Food and Drug Administration Drugs@FDA: FDA Approved Drug Products Product Labeling https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761107s000lbl.pdf  Accessed November 29, 2018.

U.S. Food and Drug Administration FDA News Release https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626263.htm Accessed November 29, 2018.

 

Additional 2018 Pipeline Reviews are available in our pipeline library.

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