PRINCIPAL DISPLAY PANEL - 150 mL Bag Carton

FERRING
PHARMACEUTICALS

NDC 55566-9800-2

1 single-dose
Rx Only

fecal microbiota, live-jslm
REBYOTA™

For rectal administration only.

Store and thaw in this carton.

Store the REBYOTA carton in an ultracold freezer
(-60°C to -90°°C, -76°F to -130°F). Alternatively, store in a
refrigerator (2°C to 8°C, 36°F to 46°F) for up to 5 days
(including thaw time). Do not refreeze REBYOTA after thawing.

Before Using:

Prior to use, thaw REBYOTA completely by placing carton
in a refrigerator (2°C to 8°C, 36°F to 46°F) for approximately
24 hours. Do not refreeze REBYOTA after thawing.

Condensation is normal
after thawing.

Contents:
One inner carton containing
a suspension bag of a single
150 mL dose of REBYOTA.

Use with the Administration Set
provided in a separate carton.

1 INDICATIONS AND USAGE

REBYOTA is indicated for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibiotic treatment for recurrent CDI.

Limitation of Use:

REBYOTA is not indicated for treatment of CDI.

5 WARNINGS AND PRECAUTIONS

5.1 Transmissible infectious agents

Because REBYOTA is manufactured from human fecal matter it may carry a risk of transmitting infectious agents. Any infection suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Ferring Pharmaceuticals Inc.

5.2 Management of acute allergic reactions

Appropriate medical treatment must be immediately available in the event an acute anaphylactic reaction occurs following administration of REBYOTA.

5.3 Potential presence of food allergens

REBYOTA is manufactured from human fecal matter and may contain food allergens. The potential for REBYOTA to cause adverse reactions due to food allergens is unknown.

6 ADVERSE REACTIONS

The most commonly reported (≥ 3%) adverse reactions occurring in adults following a single dose of REBYOTA were abdominal pain, (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%).

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of REBYOTA was evaluated in 2 randomized, double-blind clinical studies (Study 1: NCT03244644 and Study 2: NCT02299570) and 3 open-label clinical studies (NCT01925417, NCT02589847, NCT03931941) conducted in the United States and Canada. A total of 978 adults 18 years of age and older with a history of 1 or more recurrences of Clostridioides difficile (CDI) infection and whose symptoms were controlled 24 – 72 hours post-antibiotic treatment were enrolled and received 1 or more doses of REBYOTA; 595 of whom received a single dose of REBYOTA. In the 2 randomized, double-blind clinical studies, 131 adults were originally randomized to receive placebo and 48 crossed over to receive an open-label dose of REBYOTA after additional CDI recurrence. Overall, across the 5 studies, the median age of participants was 64 years and 67.2 % were female. The racial and ethnic distribution was as follows: 93.8% were white, and 2.4% were of Hispanic or Latino ethnicity. No meaningful differences in demographic characteristics occurred across the treatment groups. Study 1 and Study 2 excluded individuals with celiac disease, Inflammatory Bowel Disease, Irritable Bowel Syndrome, and chronic diarrhea. Individuals with these conditions were not excluded from one of the open-label studies (NCT03931941), and individuals with food allergies were not excluded from any of the 5 clinical studies.

Adverse Reactions

Across the 5 clinical studies, participants recorded solicited adverse events in a diary for the first 7 days after each dose of REBYOTA or placebo. Participants were monitored for all other adverse events by queries during scheduled visits, with duration of follow-up ranging from 6 to 24 months after the last dose. In Study 1, a multi-center, double-blind randomized (2:1), placebo-controlled trial conducted in the United States and Canada, 180 adults 18 years of age and older received a single dose of REBYOTA and 87 received placebo. Participants with a recurrence of CDI (rCDI) during the first 8 weeks after receipt of REBYOTA or placebo were censored from analysis at the time of rCDI. During the first two weeks following a dose of REBYOTA or placebo, 34 participants (18.9%) and 24 participants (27.6%) respectively, were censored. Overall, during the 8 week follow up period, 47 REBYOTA recipients (26.1%) and 30 placebo recipients (34.5%) were censored from analysis. In an analysis of solicited and unsolicited adverse events reported in Study 1, the most common adverse reactions (defined as adverse events assessed as definitely, possibly, or probably related to Investigational Product by the investigator) reported by ≥3% of REBYOTA recipients, and at a rate greater than that reported by placebo recipients, were abdominal pain, (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%) (Table 1).

Table 1: Adverse Reactions* reported by ≥3% of REBYOTA recipients, and at a rate greater than that reported by placebo recipients, within 8 weeks after receipt of REBYOTA or placebo (Study 1).

Adverse Reaction	REBYOTA N=180 n (%)	Placebo N=87 n (%)
Adverse reactions were defined as solicited and unsolicited adverse events that were assessed as definitely, possibly or probably related to treatment by the study investigator.
Abdominal Pain	16 (8.9)	6 (6.9)
Diarrhea	13 (7.2)	3 (3.4)
Abdominal distension	7 (3.9)	2 (2.3)
Flatulence	6 (3.3)	0
Nausea	6 (3.3)	1 (1.1)

Most adverse reactions occurred during the first 2 weeks after treatment. After this, the proportion of patients with adverse reactions declined in subsequent 2-week intervals. Beyond 2 weeks after treatment only a few single adverse reactions were reported. Most adverse drug reactions were mild to moderate in severity. No life-threatening adverse reaction was reported.

Serious Adverse Reactions

In a pooled analysis of the 5 clinical studies, 10.1% (60/595) of REBYOTA recipients (1 dose only) and 7.2% (6/83) of placebo recipients reported a serious adverse event within 6 months post last dose of investigational product. None of these events were considered related to the investigational product.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

REBYOTA is not absorbed systemically following rectal administration, and maternal use is not expected to result in fetal exposure to the drug.

8.2 Lactation

REBYOTA is not absorbed systemically by the mother following rectal administration, and breastfeeding is not expected to result in exposure of the child to REBYOTA.

8.4 Pediatric Use

Safety and effectiveness of REBYOTA in individuals younger than 18 years of age have not been established.

8.5 Geriatric Use

Of the 978 adults who received REBYOTA, 48.8% were 65 years of age and over (n=477), and 25.7% were 75 years of age and over (n=251). Data from clinical studies of REBYOTA are not sufficient to determine if adults 65 years of age and older respond differently than younger adults.