These Highlights Do Not Include All The Information Needed To Use Vowst™ Safely And Effectively. See Full Prescribing Information For Vowst.

Limitation of Use:

VOWST is not indicated for treatment of CDI.

Store VOWST in the original packaging at 2° to 25°C (36° to 77°F). Do not store in the freezer.

VOWST (fecal microbiota spores, live-brpk) is a bacterial spore suspension in capsules for oral administration. VOWST is manufactured from human fecal matter sourced from qualified donors. Human fecal matter donations are routinely tested for a panel of transmissible pathogens. Donors do not have dietary restrictions with respect to potential food allergens. The spore suspension is generated by treating fecal matter with ethanol to kill organisms that are not spores, followed by filtration steps to remove solids and residual ethanol. Each capsule of VOWST contains between 1×10⁶ and 3×10⁷ Firmicutes spore colony forming units in 92 ± 4% (w/w) glycerol in saline.

The safety and effectiveness of VOWST in individuals younger than 18 years of age have not been established.

Of the 349 adults who received VOWST, 52.4% were 65 years of age and over (n=183), and 28.1% were 75 years of age and over (n=98). Data from clinical studies of VOWST are not sufficient to determine if adults 65 years of age and older respond differently than younger adults.

• The dosage of VOWST is 4 capsules taken orally once daily for 3 consecutive days.
• Take each dose (4 capsules) on an empty stomach prior to the first meal of the day.

The efficacy of VOWST was evaluated in a randomized placebo-controlled multi-center study (Study 1). The primary objective was to demonstrate the reduction of CDI recurrence with VOWST. Enrolled participants were 18 years of age or older and had a confirmed diagnosis of recurrent CDI (with a total of ≥3 episodes of CDI within 12 months). CDI episode at the study entry was defined as diarrhea (≥3 unformed stools per day for at least 2 consecutive days) and a positive C. difficile stool sample using a toxin assay. Participants were required to have symptom resolution, defined as <3 unformed stools in 24 hours for 2 or more consecutive days prior to randomization, following 10 to 21 days of standard-of-care antibacterial treatment with vancomycin or fidaxomicin. Participants were stratified by antibacterial received (vancomycin or fidaxomicin) and age (<65 years or ≥65 years) and randomized 1:1 to receive a dose of VOWST or placebo once daily for 3 consecutive days. The day prior to starting the assigned treatment regimen, participants were required to drink 296 mL (10 oz) of magnesium citrate or based on medical judgment, 250 mL polyethylene glycol electrolyte solution (GoLYTELY, not approved for this use). Participants with impaired kidney function who were unable to take magnesium citrate took 250 mL polyethylene glycol electrolyte solution. All participants fasted for at least 8 hours before taking the first dose of VOWST. Participants were also required to continue fasting for 1 hour after the first day of treatment with VOWST. For Days 2 and 3, VOWST was taken in the morning before breakfast.

In the intent-to-treat population consisting of all 182 randomized participants, 89 were in the VOWST group and 93 were in the placebo group. The participants had a mean age of 65.5 years (range, 18–100 years), 93.4% were white, 59.9% were female, and 73.1% received vancomycin.

The primary efficacy endpoint was CDI recurrence through 8 weeks after completion of treatment. Participants were assessed for recurrence, which was defined as ≥3 unformed stools per day for 2 consecutive days with continued diarrhea until antibacterial treatment was initiated, a positive C. difficile test on a stool sample determined by a toxin assay, and assessment by the Investigator that the clinical condition of the participant warranted antibacterial treatment.

Through 8 weeks after treatment, CDI recurrence in VOWST-treated participants was lower compared to that in placebo-treated participants (12.4% compared to 39.8%). VOWST met the pre-specified success criterion of the upper bound of the two-sided 95% confidence interval of the CDI relative risk lower than 0.83 (see Table 2).

Through 12 weeks after treatment, the recurrence rates for VOWST and placebo recipients were 18.0% (16/89) and 46.2% (43/93), respectively with a relative risk of 0.40 (95% CI 0.24,0.65). Through 24 weeks after treatment, recurrence rates for VOWST and placebo recipients were 21.3% (19/89) and 47.3% (44/93), respectively with a relative risk of 0.46 (95% CI 0.30, 0.73).

None.

The most common adverse reactions (reported in ≥5% of participants) were abdominal distension (31.1%), fatigue (22.2%), constipation (14.4%), chills (11.1%), and diarrhea (10.0%).

VOWST contains bacterial spores; therefore, antibacterials should not be administered concurrently with VOWST.

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).

The mechanism of action of VOWST has not been established.

For oral administration only. (2)

• Prior to taking the first dose:
  • Complete antibacterial treatment for rCDI 2 to 4 days before initiating treatment with VOWST. (2.1)
  • Drink 296 mL (10 oz) of magnesium citrate on the day before and at least 8 hours prior to taking the first dose of VOWST. In clinical studies, participants with impaired kidney function received polyethylene glycol electrolyte solution (250 mL GoLYTELY, not approved for this use). (2.1)
• The dosage of VOWST is 4 capsules taken orally once daily for 3 consecutive days. (2.2)
• Take each dose (4 capsules) on an empty stomach prior to the first meal of the day. (2.2)

Capsule. A single dose is 4 capsules.

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 VOWST was evaluated in one Phase 3, randomized, double-blind clinical study (Study 1: NCT03183128) and one Phase 3, open-label clinical study (Study 2: NCT03183141) conducted in the United States and Canada. Adults with confirmed rCDI were required to have symptoms controlled 48 to 96 hours post-antibacterial treatment to be eligible for enrollment and randomization (1:1) to receive either VOWST or placebo (capsules containing 92 ± 4% glycerol in saline) for 3 consecutive days. Participants with neutropenia (absolute neutrophil count of <500 cells/mm³), toxic megacolon, or small bowel ileus were excluded from these studies. A total of 349 adults 18 years of age and older with rCDI were exposed to VOWST across both Study 1 (n=90) and Study 2 (n=259). Across both Study 1 and Study 2, 99.1% of adults (346/349) received all scheduled doses of VOWST. Overall, across the 2 studies, the median age of VOWST recipients was 66 years (range, 21-100 years). The racial and ethnic distribution was as follows: 92.3% were white and 5.2% were black. In Study 1, females comprised 68.9% of the VOWST arm compared to 51.1% in the placebo arm. Rates of the following comorbidities (at study entry) were similar across the VOWST and placebo arms: cardiac disease (33.3% and 31.5%, respectively), immunocompromise/immunosuppression (28.9% and 30.4%, respectively), diabetes (20.0% and 27.2%, respectively), and renal impairment (14.4% and 15.2%, respectively). In Study 2, 68.4% were females and representation of comorbidities was similar to Study 1.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Inform patients not to take VOWST concurrently with antibacterials [see Drug Interactions (7)].

• Complete antibacterial treatment for recurrent CDI 2 to 4 days before initiating treatment with VOWST.
• Drink 296 mL (10 oz) magnesium citrate, on the day before and at least 8 hours prior to taking the first dose of VOWST. In clinical studies, participants with impaired kidney function received polyethylene glycol electrolyte solution (250 mL GoLYTELY, not approved for this use) [see Clinical Studies (14)].
• Do not eat or drink, except for small amount of water, for at least 8 hours prior to taking the first dose.

Because VOWST is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Any infection suspected by a healthcare provider possibly to have been transmitted by this product should be reported by the healthcare provider to Aimmune Therapeutics, Inc. at 1-833-246-2566.

VOWST is supplied as capsules in bottles with child-resistant caps. Each bottle contains 12 white capsules imprinted with "SER109". Each bottle is supplied in a carton.

Bottles of 12 capsules: NDC 71881-400-12.

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

fecal microbiota

spores, live-brpk

VOWST^®

Contents: One bottle containing 12 capsules

Distributed by Aimmune Therapeutics, Inc.

NDC 71881-400-12

Rx Only

VOWST has not been evaluated for carcinogenicity, genotoxicity, mutagenic potential, or impairment of male or female fertility in animals.

Limitation of Use:

VOWST is not indicated for treatment of CDI.

Store VOWST in the original packaging at 2° to 25°C (36° to 77°F). Do not store in the freezer.

VOWST (fecal microbiota spores, live-brpk) is a bacterial spore suspension in capsules for oral administration. VOWST is manufactured from human fecal matter sourced from qualified donors. Human fecal matter donations are routinely tested for a panel of transmissible pathogens. Donors do not have dietary restrictions with respect to potential food allergens. The spore suspension is generated by treating fecal matter with ethanol to kill organisms that are not spores, followed by filtration steps to remove solids and residual ethanol. Each capsule of VOWST contains between 1×10⁶ and 3×10⁷ Firmicutes spore colony forming units in 92 ± 4% (w/w) glycerol in saline.

The safety and effectiveness of VOWST in individuals younger than 18 years of age have not been established.

Of the 349 adults who received VOWST, 52.4% were 65 years of age and over (n=183), and 28.1% were 75 years of age and over (n=98). Data from clinical studies of VOWST are not sufficient to determine if adults 65 years of age and older respond differently than younger adults.

• The dosage of VOWST is 4 capsules taken orally once daily for 3 consecutive days.
• Take each dose (4 capsules) on an empty stomach prior to the first meal of the day.

The efficacy of VOWST was evaluated in a randomized placebo-controlled multi-center study (Study 1). The primary objective was to demonstrate the reduction of CDI recurrence with VOWST. Enrolled participants were 18 years of age or older and had a confirmed diagnosis of recurrent CDI (with a total of ≥3 episodes of CDI within 12 months). CDI episode at the study entry was defined as diarrhea (≥3 unformed stools per day for at least 2 consecutive days) and a positive C. difficile stool sample using a toxin assay. Participants were required to have symptom resolution, defined as <3 unformed stools in 24 hours for 2 or more consecutive days prior to randomization, following 10 to 21 days of standard-of-care antibacterial treatment with vancomycin or fidaxomicin. Participants were stratified by antibacterial received (vancomycin or fidaxomicin) and age (<65 years or ≥65 years) and randomized 1:1 to receive a dose of VOWST or placebo once daily for 3 consecutive days. The day prior to starting the assigned treatment regimen, participants were required to drink 296 mL (10 oz) of magnesium citrate or based on medical judgment, 250 mL polyethylene glycol electrolyte solution (GoLYTELY, not approved for this use). Participants with impaired kidney function who were unable to take magnesium citrate took 250 mL polyethylene glycol electrolyte solution. All participants fasted for at least 8 hours before taking the first dose of VOWST. Participants were also required to continue fasting for 1 hour after the first day of treatment with VOWST. For Days 2 and 3, VOWST was taken in the morning before breakfast.

In the intent-to-treat population consisting of all 182 randomized participants, 89 were in the VOWST group and 93 were in the placebo group. The participants had a mean age of 65.5 years (range, 18–100 years), 93.4% were white, 59.9% were female, and 73.1% received vancomycin.

The primary efficacy endpoint was CDI recurrence through 8 weeks after completion of treatment. Participants were assessed for recurrence, which was defined as ≥3 unformed stools per day for 2 consecutive days with continued diarrhea until antibacterial treatment was initiated, a positive C. difficile test on a stool sample determined by a toxin assay, and assessment by the Investigator that the clinical condition of the participant warranted antibacterial treatment.

Through 8 weeks after treatment, CDI recurrence in VOWST-treated participants was lower compared to that in placebo-treated participants (12.4% compared to 39.8%). VOWST met the pre-specified success criterion of the upper bound of the two-sided 95% confidence interval of the CDI relative risk lower than 0.83 (see Table 2).

Through 12 weeks after treatment, the recurrence rates for VOWST and placebo recipients were 18.0% (16/89) and 46.2% (43/93), respectively with a relative risk of 0.40 (95% CI 0.24,0.65). Through 24 weeks after treatment, recurrence rates for VOWST and placebo recipients were 21.3% (19/89) and 47.3% (44/93), respectively with a relative risk of 0.46 (95% CI 0.30, 0.73).

None.

The most common adverse reactions (reported in ≥5% of participants) were abdominal distension (31.1%), fatigue (22.2%), constipation (14.4%), chills (11.1%), and diarrhea (10.0%).

VOWST contains bacterial spores; therefore, antibacterials should not be administered concurrently with VOWST.

VOWST is indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older following antibacterial treatment for recurrent CDI (rCDI).

The mechanism of action of VOWST has not been established.

For oral administration only. (2)

• Prior to taking the first dose:
  • Complete antibacterial treatment for rCDI 2 to 4 days before initiating treatment with VOWST. (2.1)
  • Drink 296 mL (10 oz) of magnesium citrate on the day before and at least 8 hours prior to taking the first dose of VOWST. In clinical studies, participants with impaired kidney function received polyethylene glycol electrolyte solution (250 mL GoLYTELY, not approved for this use). (2.1)
• The dosage of VOWST is 4 capsules taken orally once daily for 3 consecutive days. (2.2)
• Take each dose (4 capsules) on an empty stomach prior to the first meal of the day. (2.2)

Capsule. A single dose is 4 capsules.

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 VOWST was evaluated in one Phase 3, randomized, double-blind clinical study (Study 1: NCT03183128) and one Phase 3, open-label clinical study (Study 2: NCT03183141) conducted in the United States and Canada. Adults with confirmed rCDI were required to have symptoms controlled 48 to 96 hours post-antibacterial treatment to be eligible for enrollment and randomization (1:1) to receive either VOWST or placebo (capsules containing 92 ± 4% glycerol in saline) for 3 consecutive days. Participants with neutropenia (absolute neutrophil count of <500 cells/mm³), toxic megacolon, or small bowel ileus were excluded from these studies. A total of 349 adults 18 years of age and older with rCDI were exposed to VOWST across both Study 1 (n=90) and Study 2 (n=259). Across both Study 1 and Study 2, 99.1% of adults (346/349) received all scheduled doses of VOWST. Overall, across the 2 studies, the median age of VOWST recipients was 66 years (range, 21-100 years). The racial and ethnic distribution was as follows: 92.3% were white and 5.2% were black. In Study 1, females comprised 68.9% of the VOWST arm compared to 51.1% in the placebo arm. Rates of the following comorbidities (at study entry) were similar across the VOWST and placebo arms: cardiac disease (33.3% and 31.5%, respectively), immunocompromise/immunosuppression (28.9% and 30.4%, respectively), diabetes (20.0% and 27.2%, respectively), and renal impairment (14.4% and 15.2%, respectively). In Study 2, 68.4% were females and representation of comorbidities was similar to Study 1.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Inform patients not to take VOWST concurrently with antibacterials [see Drug Interactions (7)].

• Complete antibacterial treatment for recurrent CDI 2 to 4 days before initiating treatment with VOWST.
• Drink 296 mL (10 oz) magnesium citrate, on the day before and at least 8 hours prior to taking the first dose of VOWST. In clinical studies, participants with impaired kidney function received polyethylene glycol electrolyte solution (250 mL GoLYTELY, not approved for this use) [see Clinical Studies (14)].
• Do not eat or drink, except for small amount of water, for at least 8 hours prior to taking the first dose.

Because VOWST is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Any infection suspected by a healthcare provider possibly to have been transmitted by this product should be reported by the healthcare provider to Aimmune Therapeutics, Inc. at 1-833-246-2566.

VOWST is supplied as capsules in bottles with child-resistant caps. Each bottle contains 12 white capsules imprinted with "SER109". Each bottle is supplied in a carton.

Bottles of 12 capsules: NDC 71881-400-12.

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

fecal microbiota

spores, live-brpk

VOWST^®

Contents: One bottle containing 12 capsules

Distributed by Aimmune Therapeutics, Inc.

NDC 71881-400-12

Rx Only

VOWST has not been evaluated for carcinogenicity, genotoxicity, mutagenic potential, or impairment of male or female fertility in animals.