UPLIZNA (Page 4 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No studies have been conducted to assess the carcinogenic potential of inebilizumab-cdon.

Mutagenesis

No studies have been conducted to assess the genotoxic potential of inebilizumab-cdon.

Impairment of F ertility

Intravenous administration of inebilizumab-cdon (0, 3, or 30 mg/kg/week) to human CD19 transgenic male and female mice prior to and during mating and continuing in females through gestation day 15 resulted in reduced fertility at both doses tested. A no-effect dose for adverse effects on fertility was not identified.

14 CLINICAL STUDIES

The efficacy of UPLIZNA for the treatment of NMOSD was established in Study 1 (NCT02200770), a randomized (3:1), double-blind, placebo-controlled trial that enrolled 213 patients with NMOSD who were anti-AQP4 antibody positive and 17 who were anti-AQP4 antibody negative.

Patients met the following eligibility criteria:

  1. A history of one or more relapses that required rescue therapy within the year prior to screening, or 2 or more relapses that required rescue therapy in 2 years prior to screening.
  2. Expanded Disability Status Scale (EDSS) score of 7.5 or less. Patients with an EDSS score of 8.0 were eligible if they were deemed capable of participating.
  3. Patients were excluded if previously treated with immunosuppressant therapies within an interval specified for each such therapy.

The use of immunosuppressants during the blinded phase of the trial was prohibited.

The use of oral or intravenous corticosteroids during the blinded phase of the trial was prohibited, with the exception of premedication for investigational treatment and treatment for a relapse.

Of the 213 enrolled anti-AQP4 antibody positive patients, a total of 161 were randomized to receive treatment with UPLIZNA, and 52 were randomized to receive placebo.

The baseline demographic and disease characteristics were balanced between the treatment groups. Females accounted for 94% of the study population. Fifty-two percent of patients were White, 21% Asian, and 9% Black or African American. The mean age was 43 years (range 18 to 74 years). The mean EDSS score was 4.0. The number of relapses in the two years prior to randomization was 2 or more in 83% of the patients.

UPLIZNA was administered according to the recommended dosage regimen [ see Dosage and Administration ( 2.4)] .

All potential relapses were evaluated by a blinded, independent, adjudication committee, who determined whether the relapse met protocol-defined criteria. Patients who experienced an adjudicated relapse in the randomized-controlled period (RCP), or who completed the Day 197 visit without a relapse, exited the RCP.

The primary efficacy endpoint was the time to the onset of the first adjudicated relapse on or before Day 197.

The time to the first adjudicated relapse was significantly longer in patients treated with UPLIZNA compared to patients who received placebo (relative risk reduction 73%; hazard ratio: 0.272; p < 0.0001). In the anti-AQP4 antibody positive population there was a 77.3% relative reduction (hazard ratio: 0.227, p < 0.0001). There was no evidence of a benefit in patients who were anti-AQP4 antibody negative.

Table 4 Efficacy Results in Study 1 in anti-AQP4 Antibody Positive NMOSD Patients
Treatment Group
UPLIZNA N = 161 Placebo N = 52
Time to Adjudication Committee-Determined Relapse (Primary Efficacy Endpoint)
Number (%) of patients with relapse18 (11.2%)22 (42.3%)
Hazard ratio (95% CI)a 0.227 (0.121, 0.423)
p-valuea < 0.0001

a Cox regression method, with placebo as the reference group.

Figure 1 Kaplan-Meier Plot of Time to First Adjudication Committee- D etermined NMOSD Relapse in the Randomized-Controlled Period (ITT Population ; anti-AQP4 Antibody Positive Patients )

Figure 1 Kaplan-Meier Plot of Time to First Adjudication Committee-Determined NMOSD Relapse in the Randomized-Controlled Period (ITT Population; anti-AQP4 Antibody Positive Patients)
(click image for full-size original)

Note: Numbers of patients at risk are shown at each time point.

Compared to placebo-treated patients, patients treated with UPLIZNA who were anti-AQP4 antibody positive had reduced annualized rates of hospitalizations (0.11 for UPLIZNA versus 0.50 for placebo).

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

UPLIZNA (inebilizumab-cdon) injection is a clear to slightly opalescent, colorless to slightly yellow solution supplied as:

  • One carton containing three 100 mg/10 mL single-dose vials – NDC 72677-551-01.

16.2 Storage and Handling

  • Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light.
  • Do not freeze.
  • Do not shake.
  • Store vials upright.

17 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide).

Infusion Reactions

Inform patients about the signs and symptoms of infusion reactions and advise them to contact their healthcare provider immediately if they observe signs or symptoms of infusion reactions [see Warnings and Precautions ( 5.1) ].

Infection s

Advise patients to contact their healthcare provider for any signs of infection during treatment or after the last dose. Signs include fever, chills, constant cough, or dysuria [see Warnings and Precautions ( 5.2) ].

Advise patients that UPLIZNA may cause reactivation of hepatitis B infection and that monitoring will be required if they are at risk [see Warnings and Precautions ( 5.2) ].

Advise patients that PML has happened with drugs that are similar to UPLIZNA and may happen with UPLIZNA. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Instruct the patient of the importance of contacting their healthcare provider if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [see Warnings and Precautions ( 5.2) ].

Vaccination s

Advise patients to complete any required vaccinations at least 4 weeks prior to initiation of UPLIZNA. Administration of live-attenuated or live vaccines is not recommended during UPLIZNA treatment and until B-cell recovery [see Warnings and Precautions ( 5.2)].

Pregnancy

Instruct patients that if they are pregnant or plan to become pregnant while taking UPLIZNA, they should inform their healthcare provider [see Use in Specific Populations ( 8.1)]. Advise females of reproductive potential that they should use effective contraception during treatment and for 6 months after UPLIZNA therapy [see Use in Specific Populations ( 8.3)].

Manufactured by: Viela Bio, Inc., 1 Medimmune Way, Gaithersburg, MD 20878 USA

U.S. License No. 2129

For more information, go to www.UPLIZNA.com or call 1-855-558-4352

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