APOLLO ESG System, APOLLO ESG SX System, APOLLO REVISE System, APOLLO REVISE SX System

DEN210045 · Apollo Endosurgery, Inc. · QTD · Jul 12, 2022 · Gastroenterology, Urology

Device Facts

• Record ID: DEN210045
• Device Name: APOLLO ESG System, APOLLO ESG SX System, APOLLO REVISE System, APOLLO REVISE SX System
• Applicant: Apollo Endosurgery, Inc.
• Product Code: QTD · Gastroenterology, Urology
• Decision Date: Jul 12, 2022
• Decision: DENG
• Submission Type: Direct
• Regulation: 21 CFR 876.5983
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The APOLLO ESG and ESG SX Systems are intended to be used by trained gastroenterologists or surgeons that perform bariatric procedures to facilitate weight loss by reducing stomach volume through endoscopic sleeve gastroplasty in adult patients with obesity with BMI 30 -50 kg/m^2 who have not been able to lose weight, or maintain weight loss, through more conservative measures. The APOLLO REVISE and REVISE SX Systems are intended to be used by trained gastroenterologists or surgeons that perform bariatric procedures to facilitate weight loss in adult patients with obesity with BMI 30 - 50kg/m^2 by enabling transoral outlet reduction as a revision to a previous bariatric procedure.

Device Story

Systems facilitate endoscopic sleeve gastroplasty (ESG) or transoral outlet reduction (TORe) to reduce stomach volume or gastric outlet diameter. Input: endoscopic access to gastric tissue. Operation: physician uses dual-channel (ESG/REVISE) or single-channel (ESG SX/REVISE SX) endoscope to deliver suture-anchors and cinch devices; tissue helix manipulates tissue into suturing window; needle driver creates full-thickness bites; cinch locks sutures to create plications. Output: reduced stomach capacity/outlet diameter. Used in clinical/surgical settings by trained gastroenterologists/surgeons. Output visualization via endoscope allows confirmation of construct. Clinical benefit: facilitates weight loss in patients refractory to conservative measures; provides alternative to traditional bariatric surgery.

Clinical Evidence

Supported by the prospective, multicenter MERIT Trial (NCT03406975) with 150 subjects (safety population). Primary effectiveness endpoint: %TBWL ≥10% at 52 weeks. Completers responder rate: 64.7% (Treatment) vs 4.5% (Control). Mean %TBWL at 52 weeks: 13.86% (Treatment) vs 0.76% (Control). Safety: 7.3% SAE rate; 2.3% Clavien-Dindo Grade III or higher event rate. Literature review and registry data support durability and TORe effectiveness.

Technological Characteristics

Endoscopic suturing device; includes articulating components; requires biocompatibility evaluation for patient-contacting components; requires tensile strength testing for articulating components; requires sterilization validation; shelf life testing required.

Indications for Use

Indicated for adult patients with obesity (BMI 30-50 kg/m²) who have failed to lose or maintain weight via conservative measures. Contraindicated for patients with large hiatal hernia, potential bleeding gastric lesions (ulcers, erosive gastritis, varices, vascular malformations), affective/eating disorders, pregnancy, or uncorrectable coagulopathy/anticoagulant therapy.

Regulatory Classification

Identification

This endoscopic device uses suturing to approximate gastric tissue to restrict the volume of the stomach for the intended purpose of weight loss.

Submission Summary (Full Text)

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## DE NOVO CLASSIFICATION REQUEST FOR APOLLO ESG, APOLLO ESG SX, APOLLO REVISE, APOLLO REVISE SX SYSTEMS

#### REGULATORY INFORMATION

FDA identifies this generic type of device as:

Endoscopic suturing device for altering gastric anatomy for weight loss. An endoscopic suturing device for altering gastric anatomy for weight loss uses suturing to approximate gastric tissue to restrict the volume of the stomach for the intended purpose of weight loss.

NEW REGULATION NUMBER: 21 CFR 876.5983

CLASSIFICATION: Class II

PRODUCT CODE: OTD

#### BACKGROUND

DEVICE NAME: APOLLO ESG. APOLLO ESG SX, APOLLO REVISE, APOLLO REVISE SX Systems

SUBMISSION NUMBER: DEN210045

DATE DE NOVO RECEIVED: September 30, 2021

#### SPONSOR INFORMATION:

Apollo Endosurgery, Inc. 1120 S. Capital of Texas Hwy., Bldg. 1, Ste 300 Austin. TX 78746

### INDICATIONS FOR USE

The APOLLO ESG and ESG SX Systems are intended to be used by trained gastroenterologists or surgeons that perform bariatric procedures to facilitate weight loss by reducing stomach volume through endoscopic sleeve gastroplasty in adult patients with obesity with BMI 30 -50 kg/m2 who have not been able to lose weight, or maintain weight loss, through more conservative measures.

The APOLLO REVISE and REVISE SX Systems are intended to be used by trained gastroenterologists or surgeons that perform bariatric procedures to facilitate weight loss in adult patients with obesity with BMI 30 - 50 kg/m² by enabling transoral outlet reduction as a revision to a previous bariatric procedure.

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## LIMITATIONS

The sale, distribution, and use of APOLLO ESG. ESG SX. REVISE and REVISE SX Systems are restricted to prescription use in accordance with 21 CFR 801.109.

In the clinical study of the device, patients were required to supplement device use with a low-calorie, healthy lifestyle intervention program.

APOLLO ESG, ESG SX, REVISE and REVISE SX Systems should only be used by gastroenterologists and surgeons who have undergone specific training by the device manufacturer.

APOLLO ESG, ESG SX, REVISE and REVISE SX Systems are contraindicated for use under the following conditions:

- . This system is not for use where endoscopic interventions are contraindicated.
- . This system is not for use on malignant tissue.
- Large hiatal hernia. .
- Potential bleeding gastric lesions (e.g. ulcers; erosive gastritis; varices; or vascular . malformations).
- . Affective disorders not under medical supervision or refractory to medical therapy and all eating disorders (e.g. anorexia nervosa; binge eating disorder; specified feeding and eating disorders; avoidant restrictive food intake; rumination).
- . Women who are pregnant.
- Coagulopathy and antiplatelet/anticoagulant therapy that cannot be corrected. .

PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.

### DEVICE DESCRIPTION

Endoscopic Sleeve Gastroplasty (ESG) is an endoscopic procedure that involves the creation of plications in the stomach to reduce stomach volume. The plications form a sleeve, which reduces stomach capacity and slows gastric emptying.

Patients having previous Roux-en-Y gastric bypass bariatric surgery may experience dilation of the gastrojejunostomy outlet and the gastric pouch, followed by weight gain. This can be addressed by reducing the diameter of the gastric outlet by suturing. This procedure is often referred to as Transoral Outlet Reduction (TORe).

The APOLLO ESG and APOLLO REVISE Systems are designed to accomplish ESG and TORe, respectively, using a dual channel scope. The APOLLO ESG and APOLLO REVISE System components and the respective quantities are shown in Table 1 below.

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| Component | APOLLO<br>ESG | APOLLO<br>REVISE |
|----------------------------------------------------------------------------------------------------|---------------|------------------|
| OverStitch Handle (ESS-G02-160) to perform suture manipulations. | 1 | 1 |
| Tissue Helix (THX-165-028) to bring tissue into the suturing window. | 1 | 1 |
| Suture-anchors (PLY-G02-020-APL or PLY-G02-020-A, depending on<br>geography) to affect plications. | 8 | 6 |
| Cinch devices (CNH-G01-000) to lock the sutures in place. | 8 | 6 |

## Table 1: Components and quantities for APOLLO FSG and APOLLO REVISE Systems

The APOLLO ESG SX and APOLLO REVISE SX Systems are designed to accomplish ESG and TORe. respectively, using a single channel endoscope. The APOLLO ESG SX and APOLLO REVISE SX System components and the respective quantities are shown in Table 2 below.

Table 2: Component and quantities for APOLLO ESG SX and APOLLO REVISE SX Systems

| Component | APOLLO<br>ESG SX | APOLLO<br>REVISE SX |
|----------------------------------------------------------------------------------------------------|------------------|---------------------|
| OverStitch SX Handle (ESS-G02-Sx1) to perform suture manipulations. | 1 | 1 |
| Tissue Helix (THX-165-028) to bring tissue into the suturing window. | 1 | 1 |
| Suture-anchors (PLY-G02-020-APL or PLY-G02-020-A, depending on<br>geography) to affect plications. | 8 | 6 |
| Cinch devices (CNH-G01-000) to lock the sutures in place. | 8 | 6 |

The systems function by delivering the suture to the targeted area to create full thickness bites when approximating soft tissue. The representative final construct is shown in Figure 1, illustrating how the system approximates soft tissue.

Image /page/2/Picture/12 description: The image shows a surgical setup with various components labeled. A "CoCr/316L Anchor" is visible, along with "Polypropylene Suture" that appears to be stitched into the tissue. Additionally, a "PEEK Cinch (plug and collar)" is present, likely used to secure the suture. The setup suggests a medical or surgical procedure involving tissue repair or fixation.

Figure 1: Representation of a final construct, including the polypropylene suture completing two stitches, and the anchor and cinch device components functioning as T-fasteners.

The device components are as follows:

- . The OverStitch (SX) Handle is comprised of a needle driver assembly and anchor exchange (Figure 2). The end cap contains a needle body which exchanges an anchor with the anchor exchange to perform the stitching operations. The opening and closing of the suturing arm are controlled by the handle grip. The anchor exchange allows for the endoscopic loading and recapture of a suture-anchor assembly, Once the sutures are

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placed, the anchor is released, allowing it to function as a tissue anchor, and the anchor exchange is removed.

Image /page/3/Picture/1 description: The image contains several diagrams of a surgical tool. The diagrams show the different parts of the tool, including the needle driver, actuation cable, scope, and suture. The tool has three available channels and is used for minimally invasive surgery.

Figure 2: Top: OverStitch Handle pictured with suture at distal end. Bottom: OverStitch SX Handle pictured with suture and Tissue Helix at distal end.

- The Tissue Helix enables the user to manipulate and position tissue before and after . suturing (Figure 3).

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Image /page/4/Picture/0 description: The image shows three different medical instruments. The first instrument is a long, thin needle with a blue handle and a white body. The second instrument is a gray, cylindrical device with a coiled spring at the end. The third instrument is a silver, metallic device with a clamp and a small container.

Figure 3: Top: general image of the Tissue Helix; bottom left: distal end of the Tissue Helix; bottom right: distal end of Tissue Helix shown in the endoscope channel with the OverStitch Handle.

- The Suture Anchor (Figure 4) consists of a polypropylene suture attached to a metal . piece. The metal piece serves as the needle for piercing tissue and then as a pin (Tfastener) that holds tension on one end of the suture, in the final construct (see Figure 1).
Image /page/4/Picture/3 description: The image shows a gray, oval-shaped object with a white border. The object has a hollow interior with a few small, gray structures inside. A blue line runs along the inside edge of the object, and there are a few small holes in the surface.

Image /page/4/Picture/4 description: The image shows a metal tool with a sharp, pointed end. A blue wire is connected to the tool near the opposite end of the pointed tip. The tool appears to be designed for piercing or penetrating materials, possibly for electrical or measurement purposes. The background is plain, which helps to highlight the tool and its features.

Figure 4: Left: Suture Anchors as packaged; right: Suture-Anchor Assembly

- . The Cinch device (Figure 5) is a plastic component that simultaneously cuts the suture and clamps onto the suture. It serves as a second T-fastener that holds tension on the other end of the suture, in the final construct (see Figure 1).
Image /page/4/Picture/7 description: The image shows a medical device, possibly a biopsy instrument, with a handle that has finger loops for manipulation. The device has a long, thin shaft extending from the handle, with an orange marker near the tip. The tip of the device appears to have a small hook or needle-like structure, suggesting it is designed for precise tissue sampling or manipulation. The device is likely used in minimally invasive procedures for diagnostic or therapeutic purposes.

Figure 5: Cinch device

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# SUMMARY OF NONCLINICAL/BENCH STUDIES

The non-clinical/bench studies conducted on the APOLLO ESG, ESG SX, REVISE and REVISE SX Systems are summarized below. The APOLLO ESG, ESG SX. REVISE and REVISE SX Systems are identical in design to the OverStitch Systems previously cleared for marketing (K081853, K171886, K181141, K191439, and K210266) for a different intended use. Notations of non-clinical information that were relied upon and/or leveraged from prior marketing submissions to support the De Novo request are summarized in the information below.

# STERILITY AND SHELF LIFE

The APOLLO ESG, ESG SX, REVISE and REVISE SX Systems are provided sterile and intended for single patient use. Documentation previously submitted to FDA in marketing submissions (K081853, K171886, K191439, and K210266) regarding ethylene oxide sterilization validation, bacterial endotoxin testing, and package integrity is applicable to the subject device systems and supports that the device systems have a sterility assurance level (SAL) of (0) and can maintain sterility for the duration of the labeled shelf life.

Packaging integrity was evaluated in accordance with the following industry standards to confirm the packaging design provides an adequate protective barrier.

- ASTM D4169-16- Standard Practice for Performing Testing of Shipping Containers and . Systems
- . ASTM F2096-11- Standard Test Method for Detecting Gross Leaks in Packaging by Internal Pressurization
- . ASTM F88/F88M-15- Standard Test Method for Seal Strength of Flexible Barrier Materials
- ASTM F1980-16) Standard Guide for Accelerated Aging of Sterile Barrier Systems for . Medical Devices

Functional testing previously submitted to FDA in marketing submissions (K171886, K191439. K210266) supports that the device systems can function of the labeled shelf life. Stability studies on aged devices included evaluations of device mechanical strength and comprehensive functional testing as outlined in Table 3.

# BIOCOMPATIBILITY

APOLLO ESG. ESG SX, REVISE and REVISE SX System components: OverStitch (SX) Handle, Tissue Helix, and Cinch device are classified as mucosal membrane contacting for limited duration (≤ 24 hours).

APOLLO ESG. ESG SX. REVISE and REVISE SX System Suture Anchors are classified as breached or compromised surface contacting for permanent duration (> 30 days).

To support biocompatibility, appropriate biocompatibility assessments in accordance with ISO 10993-1. Biological evaluation of medical devices, and FDA Guidance: Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing

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within a risk management process" were leveraged from prior marketing submissions (K081853, K171886, K181141, K191439, and K210266).

Biocompatibility endpoints for the OverStitch (SX) Handle, Tissue Helix, and Cinch device were:

Image /page/6/Picture/2 description: The image is a rectangular shape with a red border. The inside of the rectangle is filled with a gray color. There is some text in the middle of the rectangle that says '(b)(4)'.

Biocompatibility endpoints for the Suture Anchors (shown in Figure 1) were:

Image /page/6/Picture/4 description: The image is a gray rectangle with a red border. The text '(b)(4)' is located at the top of the rectangle. The text is small and difficult to read.

Results previously assessed by FDA support the biocompatibility of the APOLLO ESG, ESG SX, REVISE and REVISE SX Systems when used to place up to eight sutures and cinches.

# PERFORMANCE TESTING - BENCH

The integrity and performance of the APOLLO ESG, ESG SX, REVISE and REVISE SX Systems were evaluated with the nonclinical bench testing summarized in Table 3.

| Test | Test Methods | Acceptance Criteria | Results |
|-----------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------|
| Durability of<br>APOLLO Systems | (b)(4) suture passes were done<br>during simulated use on<br>synthetic tissue with a<br>thickness of (b)(4) | APOLLO System can deliver 64 suture<br>passes | Pass |
| Durability of Tissue<br>Helix | (b)(4) iterations of grabbing and<br>retracting synthetic tissue to<br>demonstrate that the tip did not<br>dull and the helix was not<br>adversely affected such that it<br>could not engage or release the<br>tissue | Complete at least 64 tissue acquisitions | Pass |
| Magnetic Resonance<br>Imaging (MRI)<br>compatibility of<br>implanted suture | Testing was conducted in<br>accordance with ASTM<br>F2052-02: Standard Test<br>Method for Measurement of | MRI compatibility labeling must be<br>supported by testing. To be considered<br>MRI conditional, displacement forces<br>should not have the potential to | Sutures are<br>MRI<br>conditional |

| Table 3: Summary of Performance Testing - Bench Studies | | | | | | | |
|--------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|------|---------|
| | | | | | | | |
| Test | Test Methods | Acceptance Criteria | Results | | | | |
| • Displacement force | Magnetically Induced<br>Displacement Force on Passive<br>Implants in the Magnetic<br>Resonance Environment, | damage the tissue where the device is<br>placed | | | | | |
| Previous testing leveraged from prior marketing submissions K171886 and K191439 | | | | | | | |
| APOLLO Systems<br>Design verification | (b)(4) | • System can be passed through the<br>working channel of an endoscope and<br>can be manipulated within the<br>endoscope<br>• System allows for a 360 degree full<br>range of motion on the endoscope<br>• System can be passed through the<br>working channel of an endoscope and<br>can be visualized by the endoscope<br>• System can be pre-loaded with an<br>anchor-suture prior to passing the<br>device endoscopically<br>• System can be reloaded with a needle<br>and suture endoscopically<br>• System can obtain tissue to pass<br>suture through tissue<br>• Tissue Helix can be advanced up to<br>collar and retracted into the<br>endoscope without failure<br>• System can deliver a suture through<br>various tissue<br>• Anchor-suture assembly placement<br>can be visually confirmed<br>endoscopically<br>• System can secure a suture through<br>the working channels of an endoscope<br>• The Cinch attachment strength, for all<br>suture types, shall maintain a<br>minimum suture retention force of 2.4<br>lbf. | Pass | | | | |
| Polypropylene suture<br>verification | Test | • Suture-needle attachment<br>(b)(4)<br>• Tensile Strength (b)(4)<br>(b)(4)<br>• Suture diameter (b)(4)<br>(b)(4) | Test Methods | • The tensile strength for the Anchor to<br>the Suture in a T-tag configuration<br>must be ≥ 1.10 kgf<br>• The average knot-pull tensile strength<br>of the Suture must be ≥ 1.44 kgf<br>• The average Suture diameter must be<br>between 0.300 mm and 0.339 mm.<br>• The force required to pull 6 inches of<br>suture through the endoscope (or<br>Anchor Exchange Channel for SX | Acceptance Criteria | Pass | Results |
| MRI compatibility of<br>implanted suture<br>· Magnetically<br>induced heating<br>· Artifact assessment | ASTM F2182-02a: Standard<br>Test Method for Measurement<br>of Radio Frequency Induced<br>Heating Near Passive Implants<br>During Magnetic Resonance<br>Imaging, and ASTM F2119-<br>01: Standard Test Method for<br>Evaluation of MR Image<br>Artifacts from Passive<br>Implants | MRI compatibility labeling must be<br>supported by testing. To be considered<br>MRI conditional, temperature increases<br>should not damage tissues when<br>patients are scanned as outlined in the<br>labeling | Sutures are<br>MRI<br>conditional | | | | |

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## SUMMARY OF CLINICAL INFORMATION

Clinical data from a pivotal study (MERIT Trial), real-world registry data, peer-reviewed literature, and post-market surveillance were leveraged to evaluate the safety and effectiveness of the APOLLO ESG, ESG SX, REVISE and REVISE SX Systems.

## MERIT Trial

The Multi-center ESG Randomized Interventional (MERIT) Trial (ClinicalTrials.gov, NCT03406975) evaluated the effectiveness and safety of ESG as an adjunct to life-style intervention for weight loss compared to lifestyle intervention alone in participants 21-65 years of age with BMI >30 and <40 kg/m2 who had failed to achieve and maintain weight loss with a non-surgical program. The study aimed to enroll at least 50 patients with hypertension, at least 50 with Type II diabetes mellitus (T2DM), and to enroll no more than 50 patients with no weight-related comorbidities.

This was a prospective, randomized, multicenter study and subjects were followed for two years. Patients were randomized in a 1:1.5 ratio of treatment (ESG + lifestyle modification) to control (lifestyle modification). At one year, patients in the Control group were allowed to cross-over to ESG if they had not responded to lifestyle modification (defined as not having achieved >25% Excess Weight Loss (EWL')) and had completed their follow-up visits.

The multicenter study (9 U.S. sites) was sponsored by the MAYO Clinic (Rochester, MN) and financial support was provided by Apollo Endosurgery, Inc. as part of a collaborative research agreement. The study data were compiled by the MAYO Clinic and provided to Apollo Endosurgery for independent analysis. Apollo's analysis of the MERIT Trial outcomes were used to support a reasonable assurance of safety and effectiveness.

^· Excess Body Weight Loss (EWL), which assumes an ideal BMI of 25 kg/m2 and uses height (h) measured in inches, was calculated as follows: ideal weight(b.) = (25 x h2)/703; excess weight (lb.) = initial weight (lb.) = ideal weight (1b.); %EWL=[TBWL (lb.) (excess weight (lb.)] x 100%

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# Endpoints

The population for the effectiveness analysis was the modified intent-to-treat (mITT) population. which included all eligible subjects regardless of adherence to follow-up visits or the treatment program. The mITT population was defined as follows:

- . Subjects in both groups that met the eligibility criteria for the study.
- Treatment subjects that had an esophagogastroduodenoscopy (EGD) with o confirmation of satisfying anatomical and medical criteria and completed the ESG.
- Treatment and Control subjects that were confirmed ineligible based upon baseline O visit information, were excluded from study analysis, even if the subject completed study visits prior to exclusion.
- Subjects in the Control group that completed at least one follow-up visit following . randomization.

The population for the safety analysis included all patients that were assigned to have an ESG procedure, either as randomized or as a cross-over from lifestyle intervention alone to the ESG group.

The Completers population is defined as those mITT subjects that completed the 52-week visit.

### Primary Effectiveness endpoint

The primary effectiveness endpoint of Apollo's analysis was the percentage of subjects who were responders to treatment at 52 weeks follow-up, where response was defined as achieving ≥10% Total Body Weight Loss (%TBWL2). The %TBWL was derived at each post-placement study visit for each subject where a weight measurement was collected.

### Primary Safety endpoint

The primary safety endpoint was the percentage of subjects having device and procedure related adverse events with Clavien-Dindo3 Grade III or higher at 52 weeks following ESG treatment. Grade III events require surgical, endoscopic, and/or radiological intervention; Grade IV events are life-threatening; and death is the Grade V event. All adverse events were recorded.

### Secondary endpoints

Secondary endpoints collected as part of Apollo's analysis included %EWL and change in BMI from baseline. Along with %TBWL, these data were collected at each visit and used to evaluate the effectiveness of Treatment and Control, retightening of an ESG, and crossing over from lifestyle modification to ESG, over time.

### Subject disposition

259 subjects provided informed consent and 209 subjects were randomized: 85 Treatment and 124 Control. Eight subjects in the Treatment group did not receive treatment, because they did not meet eligibility criteria; they were removed from the study. Twelve subjects in the Control

² Percent Total Body Weight Loss (%TBWL), was calculated as follows: [(final weight (1b.) - initial weight (1b.) / (initial weight (lb.))] X 100%

³ Dindo. D., Demartines, N., & Clavien, P. A. (2004). Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery, 240(2), 205.

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group did not complete any study visits and were removed from the study. Two additional Control subjects were determined to be ineligible prior to starting the study. As a result, 77 Treatment and 110 Control subjects received the assigned treatment. Three Treatment subjects withdrew consent prior to the 52 week visit and six were lost to follow-up. In the Control group. 13 withdrew consent and eight were lost to follow-up prior to completing the 52 week visit. As a result, there were 68 Treatment and 89 Control subjects with effectiveness data at 52 weeks (Figure 6). Of the subjects with data at 52 weeks; 55 and 113 had baseline comorbidities of T2DM or hypertension, respectively, defined as a having a pre-existing diagnosis from their primary care physician and currently taking medications specifically for that comorbidity. Of those, 37 subjects had both baseline diagnosis of both diabetes and hypertension.

Image /page/10/Figure/1 description: This image is a flowchart that shows the progression of subjects through a study. The study starts with 259 subjects who consented to participate. Of those, 50 were not eligible, and 209 were randomized. The randomized subjects were split into two groups: an ESGA group with 85 subjects and a control group with 124 subjects. The ESGA group had 8 subjects who were not treated, 77 subjects who were treated, 3 subjects who withdrew consent, 6 subjects who were lost to follow-up, and 68 subjects who completed 52 weeks. The control group had 2 subjects who were not eligible, 12 subjects who were not treated, 110 subjects who were treated, 13 subjects who withdrew consent, 8 subjects who were lost to follow-up, and 89 subjects who completed 52 weeks.

Figure 6: Schematic overview of subject accounting for each randomized group from consent through 52 weeks follow-up. The ITT population for each randomized group is identified by "A'. the mITT population for each randomized group is identified by '*' and the completers population is identified by '#'.

At the conclusion of the first year of treatment, 89 Control subjects were evaluated for progression to the cross-over ESG procedure. A visual overview of the subject population for the cross-over subject follow-up is provided in Figure 7. Control subjects were ineligible for the cross-over ESG if they were found to be ineligible at the EGD and the procedure was terminated before the device was introduced into the subject.

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Image /page/11/Figure/0 description: This image is a flowchart showing the progress of subjects through a 52-week follow-up study. The study began with 89 subjects who completed the 52-week follow-up. Of those, 81 were eligible and proceeded to a cross-over procedure with 73 subjects. 72 subjects completed the procedure, while 59 completed 52 weeks.

Figure 7: Schematic overview of subject accounting for tollow-up for the cross-over ESG group through 52 weeks follow-up. The safety population is identified with a ** as the device was used for all these subjects. Subjects that completed the procedure are considered the effectiveness population, as identified with a '(a)'.

Per Figures 6 and 7, 150 subjects had the ESG procedure (77 Treatment subjects and 73 Control subjects in the cross-over ESG group). These 150 subjects are the safety population of the MERIT Trial.

At the conclusion of the first year of treatment. 68 Treatment subjects were available to continue another year of follow-up. Of these subjects, 18 underwent an EGD for potential retightening. Fourteen subjects were retightened, 9 of these subjects were eligible per the protocol requirements and 5 subjects were not eligible per protocol deviations). Four were not retightened because they had intact plications. A visual overview of the subject population for the extended treatment follow-up, including subjects that underwent retightening procedures, is provided in Figure 8. The treatment group with extended follow-up had 59 subjects complete the additional 52-week visit (104 weeks total).

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Image /page/12/Figure/0 description: This image is a flowchart that shows the progress of subjects through a 52-week follow-up study. The study began with 68 subjects, and the flowchart shows how many subjects were lost to follow-up, withdrew consent, or completed the study. The flowchart also shows how many subjects underwent EGD and retightening procedures. In total, 59 subjects completed 104 weeks of the study.

Figure 8: Schematic overview of subject accounting for follow-up beyond 52 weeks for Treatment group subjects. The diagram identifies the number of subjects that underwent an EGD following the 52-week visit and the retightening status of the subjects.

## Study population demographics

Nine sites enrolled a total of 187 subjects that made up the modified Intent to Treat (mITT) population: 77 Treatment and 110 Control subjects. Table 4 provides demographic information.

| Description | Control<br>(Lifestyle<br>Modification) | Treatment<br>(ESG + Lifestyle<br>Modification) | p-value |
|---------------|----------------------------------------|------------------------------------------------|---------|
| N | 110 | 77 | |
| Weight (kg) | | | |
| Mean ± StdDev | 99.2 ± 12.775 | 98.1 ± 12.346 | 0.641 |
| Median | 97.5 | 95.3 | |
| Min, Max | 73.8, 138.7 | 74.4, 130.0 | |
| 95% CI | 96.7, 101.6 | 95.3, 100.9 | |
| BMI (kg/m²) | | | |
| Mean ± StdDev | 35.74 ± 2.6167 | 35.37 ± 2.5654 | 0.357 |
| Median | 35.78 | 35.52 | |
| Min, Max | 30.12, 39.88 | 31.01, 39.83 | |
| 95% CI | 35.25, 36.24 | 34.79, 35.96 | |
| Age (years) | | | |
| Mean ± StdDev | 45.7 ± 10.072 | 47.3 ± 9.323 | 0.269 |
| Median | 45.5 | 49.0 | |
| Min, Max | 23, 65 | 22, 64 | |
| 95% CI | 43.8, 47.6 | 45.22, 49.45 | |
| Gender | | | |
| Male | 17 (15.5%) | 9 (11.7%) | 0.525 |
| Female | 93 (84.5%) | 68 (88.3%) | |
| Race | | | |
| White | 62 (56.4%) | 53 (68.8%) | 0.136 |

Table 4: Demographics for mITT Population by Randomized Treatment Group

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| African<br>American | 14 (12.7%) | 11 (14.3%) | |
|-------------------------------|------------|------------|-------|
| Asian | 3 (2.7%) | 0 (0.0%) | |
| Hispanic / Latino | 18 (16.4%) | 11 (14.3%) | |
| Other | 9 (8.2%) | 1 (1.3%) | |
| Deferred | 4 (3.6%) | 1 (1.3%) | |
| Weight Related Comorbidities* | | | |
| T2DM | 36 (32.7%) | 19 (24.7%) | 0.234 |
| Hypertension | 72 (65.5%) | 41 (53.2%) | 0.093 |

*For Apollo's analysis, the assignment to T2DM and/or hypertension was based on an existing diagnosis from the patient's primary healthcare provider combined with taking medication specifically for that diagnosis. Subjects could be identified as having both TY2DM and hypertension.

## Effectiveness results

The primary effectiveness analysis is reported in Table 5. Responder rates at 52 weeks, as defined by achieving >10 %TBWL, in the completers population were 64.7% and 4.5% in Treatment and Control groups, respectively. Sensitivity analysis, including Last Observation Carried Forward, and Best and Worst Case Scenarios for missing data imputation, all showed a higher responder rate in the Treatment group compared to Control group. A tipping analysis was also performed to identify the number responders in each group that would no longer result in a significant difference between the two groups. The tipping analysis indicated that an additional 22 control subjects would need to be responders, or 17 fewer treatment subjects would need to be non-responders to tip the results of the analysis.

| Population | Control | Treatment | Difference | Standard<br>Error of<br>Difference | 95% CI* | p-value |
|-----------------------------|----------------|---------------|------------|------------------------------------|--------------|---------|
| Completers<br>Rate | 4/89 (4.5%) | 44/68 (64.7%) | -60.2% | 6.2% | -71.0, -46.6 | <0.001 |
| | 1.2, 11.1 | 52.2, 75.9 | | | | |
| LOCF<br>Rate | 5/110 (4.5%) | 48/77 (62.3%) | -57.8% | 5.9% | -68.2, -45.2 | <0.001 |
| | 1.5, 10.3 | 50.6, 73.1 | | | | |
| Best Case Scenario<br>Rate | 25/110 (22.7%) | 53/77 (68.8%) | -46.1% | 6.6% | -58.0, -32.2 | <0.001 |
| | 14.8, 32.5 | 57.3, 78.9 | | | | |
| Worst Case Scenario<br>Rate | 25/110 (22.7%) | 44/77 (57.1%) | -34.4% | 6.9% | -47.2, -20.3 | <0.001 |
| | 15.3, 31.7 | 45.4, 68.4 | | | | |

Table 5: Responder rates at 52 weeks, based on achievement of 10%TBWL in the mITT nonulation

# LOCF = last observation carried forward. Best case was calculated assuming that all Treatment and Control subjects lost to follow up were responders. Worst case scenario was that all Treatment subjects lost to follow-up were nonresponders but all control subjects lost to follow-up were responders.

* Confidence interval was obtained based on the Agresti-Caffo confidence interval method, without multiplicity adjustment made.

Additional analyses were performed to report responder rates at 52 weeks (10% TBWL) by various subgroups. Table 6 below shows that responder rates across the subgroups defined by

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age, gender, race, BMI, type II diabetes, and hypertension at baseline in the completers population were all higher in the Treatment group than in the Control group.

| Comparison | Sub-Group | Control | Treatment | Difference | Standard<br>Error of<br>Difference | 95% CI*<br>(%) |
|---------------------|-------------------|-------------|---------------|------------|------------------------------------|----------------|
| Age | < 50 years | 3/66 (4.5%) | 22/37 (59.5%) | -54.9% | 8.5% | -69.5, -36.7 |
| | ≥ 50 years | 1/23 (4.3%) | 22/31 (71.0%) | -66.6% | 9.2% | -80.6, -42.8 |
| Gender | Male | 0/11 (0%) | 6/9 (66.7%) | -66.7% | 15.7% | -87.8, -24.0 |
| | Female | 4/78 (5.1%) | 38/59 (64.4%) | -59.3% | 6.7% | -70.9, -44.5 |
| BMI | <35 kg/m² | 3/41 (7.3%) | 24/31 (77.4%) | -70.1% | 8.5% | -83.5, -49.5 |
| | ≥ 35 kg/m² | 1/48 (2.1%) | 20/37 (54.1%) | -52.0% | 8.4% | -66.4, -33.3 |
| Race | Caucasian | 3/51 (5.9%) | 34/47 (72.3%) | -66.5% | 7.3% | -78.4, -49.4 |
| | Non-<br>Caucasian | 1/38 (2.6%) | 10/21 (47.6%) | -45.0% | 11.2% | -64.3, -21.3 |
| Type II<br>Diabetes | Yes | 0/27 (0%) | 11/18 (61.1%) | -61.1% | 11.5% | -79.0, -34.1 |
| | No | 4/62 (6.5%) | 33/50 (66.0%) | -59.5% | 7.4% | -72.1, -43.1 |
| Hypertension | Yes | 1/55 (1.8%) | 22/37 (59.5%) | -57.6% | 8.3% | -71.6, -39.3 |
| | No | 3/34 (8.8%) | 22/31 (71.0%) | -62.1% | 9.5% | -77.3, -39.8 |

Table 6: Sub-group responder rates at 52 weeks based on achievement of at least 10% TBWL in the Completers population.

* Confidence interval was obtained based on the Agresti-Caffo confidence interval method, without multiplicity adjustment made.

The mean %TBWL is shown for each follow up visit in Table 7. Subjects in the Treatment group began to lose weight as early as the one week visit. Weight loss steadily progressed through 24 weeks (14.70 ± 5.62 %TBWL) then plateaued, with minimal weight regain at 52 weeks (13.86 ± 8.06 %TBWL). Comparatively, subjects in the Control group experienced very little weight loss through 52 weeks (0.76 ± 4.97 %TBWL).

| Weeks | Descriptive | Control | Treatment | Difference* |
|-------|---------------|--------------------|---------------------|--------------------|
| 1 | Mean ± StdDev | $0.43 \pm 1.7946$ | $-5.08 \pm 3.9745$ | $5.51 \pm 0.4890$ |
| | N | 103 | 76 | |
| | Median | 0.11 | -4.61 | |
| | Min, Max | -4.94, 4.89 | -29.00, 1.89 | |
| | 95% CI | 0.08, 0.78 | -5.99, -4.17 | 4.54, 6.48 |
| 4 | Mean ± StdDev | $-0.08 \pm 2.2065$ | $-8.47 \pm 3.9968$ | $8.39 \pm 0.5242$ |
| | N | 92 | 72 | |
| | Median | 0.00 | -8.03 | |
| | Min, Max | -7.79, 5.86 | -33.36, -1.32 | |
| | 95% CI | -0.54, 0.37 | -9.41, -7.53 | 7.35, 9.43 |
| 8 | Mean ± StdDev | $-0.42 \pm 2.7118$ | $-11.09 \pm 4.4888$ | $10.67 \pm 0.6079$ |
| | N | 90 | 70 | |
| | Median | -0.17 | -10.96 | |
| | Min, Max | -7.32, 6.06 | -35.36, -3.64 | |
| | 95% CI | -0.99, 0.15 | -12.16, -10.02 | 9.47, 11.88 |
| 12 | Mean ± StdDev | $-0.94 \pm 3.1050$ | $-13.14 \pm 4.9838$ | $12.21 \pm 0.6588$ |

Table 7: %TBWL by Randomized Group and Visit for the mITT Population

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| Weeks | Descriptive | Control | Treatment | Difference* |
|-------|---------------|----------------|-----------------|----------------|
| | N | 89 | 62 | |
| | Median | -0.55 | -11.83 | |
| | Min, Max | -8.81, 4.44 | -37.18, -3.88 | |
| | 95% CI | -1.59, -0.28 | -14.41, -11.88 | 10.79, 13.62 |
| | Mean ± StdDev | -1.36 ± 4.5586 | -14.70 ± 5.6167 | 13.34 ± 0.8172 |
| | N | 85 | 70 | |
| 24 | Median | -0.80 | -13.51 | |
| | Min, Max | -14.31, 7.49 | -29.03, 0.36 | |
| | 95% CI | -2.34, -0.38 | -16.04, -13.36 | 11.73, 14.96 |
| | Mean ± StdDev | -0.76 ± 4.9711 | -13.86 ± 8.0585 | 13.10 ± 1.1102 |
| | N | 89 | 68 | |
| 52 | Median | -0.39 | -12.88 | |
| | Min, Max | -17.62, 9.91 | -40.91, 6.84 | |
| | 95% CI | -1.81, 0.29 | -15.81, -11.91 | 10.89, 15.30 |
| | Mean ± StdDev | NA | -14.72 ± 7.9433 | NA |
| | N | NA | 57 | |
| 60 | Median | NA | -13.66 | |
| | Min, Max | NA | -34.09, 1.08 | |
| | 95% CI | NA | -16.82, -12.61 | |
| | Mean ± StdDev | NA | -13.93 ± 7.4285 | NA |
| | N | NA | 61 | |
| 72-76 | Median | NA | -12.40 | |
| | Min, Max | NA | -37.00, 0.05 | |
| | 95% CI | NA | -15.84, -12.03 | |
| | Mean ± StdDev | NA | -12.20 ± 8.5461 | NA |
| 104 | N | NA | 59 | |
| | Median | NA | -11.29 | |
| | Min, Max | NA | -34.91, 8.13 | |
| | 95% CI | NA | -14.43, -9.97 | |

* Difference = Control - Treatment and 95% CIs are not adjusted for multiplicity

The mITT populations also observed the same type of changes in %EWL and changes in BMI. At the 52 week visit, Treatment and Control subjects reported a loss of 49.81 ± 31.40 and 2.98 ± 17.97 %EWL, respectively. Similarly, BMI in Treatment and Control subjects reduced by 4.76 ± 2.57 and 0.26 ± 1.77 kg/m2, respectively, at 52 weeks.

Table 8 presents the %TBWL at each follow up visit in patients that were assigned to the Control group but crossed over to the Treatment group at 52 weeks. As early as the 1 week visit, subjects that crossed over to ESG lost more weight than they had with lifestyle modification. Weight loss steadily progressed through 24 weeks then plateaued, with minimal weight regain at 52 weeks. This was the same pattern demonstrated by subjects randomized to ESG. After 52 weeks of lifestyle modification alone, these cross-over subjects lost 0.18 ± 4.47 %TBWL. Then, 52 weeks after crossing over to ESG, these same subjects had lost 12.95 ± 8.64 %TBWL.

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| Weeks | Description | Control | Cross-Over | Difference* |
|-------|---------------|---------------|----------------|---------------|
| 1 | Mean ± StdDev | 0.38 ± 1.494 | -4.38 ± 2.165 | 4.75 ± 0.315 |
| | N | 67 | 71 | |
| | Median | 0.24 | -4.32 | |
| | Min, Max | -3.89, 4.89 | -10.27, 0.50 | |
| | 95% CI | 0.01, 0.74 | -4.89, -3.87 | 4.13, 5.38 |
| 4 | Mean ± StdDev | 0.12 ± 1.820 | -7.70 ± 2.978 | 7.82 ± 0.423 |
| | N | 63 | 70 | |
| | Median | 0.00 | -7.38 | |
| | Min, Max | -4.37, 4.78 | -16.05, 6.43 | |
| | 95% CI | -0.34, 0.57 | -8.41, -6.99 | 6.98, 8.66 |
| 8 | Mean ± StdDev | -0.34 ± 2.518 | -10.35 ± 2.855 | 10.74 ± 0.610 |
| | N | 64 | 68 | |
| | Median | -0.55 | -10.45 | |
| | Min, Max | -6.49, 5.09 | -17.68, -4.05 | |
| | 95% CI | -0.97, 0.29 | -11.04, -9.66 | 9.07, 10.93 |
| 12 | Mean ± StdDev | -0.77 ± 2.936 | -11.50 ± 4.097 | 10.91 ± 4.786 |
| | N | 67 | 69 | |
| | Median | -0.55 | -10.29 | |
| | Min, Max | -8.58, 4.44 | -28.77, -4.27 | |
| | 95% CI | -1.48, -0.05 | -12.49, -10.52 | 9.53, 11.94 |
| 24 | Mean ± StdDev | -0.69 ± 3.910 | -13.35 ± 5.77 | 12.66 ± 0.849 |
| | N | 64 | 69 | |
| | Median | -0.14 | -12.28 | |
| | Min, Max | -12.97, 7.49 | -32.36, -3.83 | |
| | 95% CI | -1.67, 0.28 | -14.74, -11.97 | 10.98, 14.34 |
| 52 | Mean ± StdDev | -0.18 ± 4.473 | -12.95 ± 8.636 | 12.77 ± 1.242 |
| | N | 72 | 59 | |
| | Median | -0.02 | -12.17 | |
| | Min, Max | -17.62, 7.11 | -36.64, 4.09 | |
| | 95% CI | -1.23, 0.87 | -15.20, -10.70 | 10.30, 15.24 |

Table 8: %TBWL Control and Cross-Over

* Difference = Control - Treatment and 95% CIs are not adjusted for multiplicity

The cross-over population also demonstrated the same type of changes in %EWL and changes in BMI. At the 52 week visit after cross-over, subjects reported a loss of 46.85 ± 37.97% compared to 0.44 ± 15.34% EWL over the 52 weeks of lifestyle modification prior to crossing over. Similarly, BMI reduced by 4.59 ± 2.10 kg/m2 52 weeks after crossing over, compared to a reduction of just 0.07 ± 1.61 kg/m2, after the 52 weeks of lifestyle modification prior to crossing over. The weight loss from subjects following cross-over was consistent with the amount of weight loss in subjects randomized to the Treatment group.

Fourteen ESG patients had a secondary procedure to retighten the original ESG procedure. At 52 weeks prior to the retightening procedure, mean weight loss was 3.84 ± 4.31% TBWL in 9 subjects that had not experienced at least 25% EWL, and 10.94 ± 3.02% TBWL in 5 subjects that had lost more than 25% EWL. This is compared to 15.8 ± 7.5% TBWL in the 54 Treatment subjects still under study at 52 weeks that were not retightened. At 104 weeks, 52 weeks after retightening, the mean weight loss from baseline (index ESG procedure) was 7.10 ± 5.1% TBWL in the < 25% EWL group (9 subjects) and 11.6 ± 7.6% TBWL in the > 25% EWL group

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(5 subjects). Similarly, %EWL and change in BMI were greater for the subjects with >25% EWL prior to the retightening procedure.

## Safety results

The safety population includes subjects from both the initial ESG group (Figure 6, 77 subjects) and cross-over ESG group (Figure 7, 73 subjects) for a total of 150 subjects. Of these 150 subjects. 146 and 131 subjects had complete safety data through 24 and 52 weeks since the ESG. respectively.

The primary safety endpoint was the percentage of subjects having device and procedure related adverse events with Clavien-Dindo Grade III or higher at 52 weeks following ESG treatment. All adverse events were recorded.

There were 935 device or procedure related adverse events reported in the study. Of the 150 subjects that had an ESG (including primary and cross-over subjects). 138 (92%) experienced at least one device or procedure related adverse event and 132 (88%) experienced at least two adverse events. Some subjects reported multiple instances of a given type of adverse event.

The observed rate of device or procedure related. Clavien-Dindo4 Grade III or higher, events was 2.3% (3/131) in the Completer population and the upper limit of the 1-sided 95% confidence interval was 6.5%. Error! Reference source not found. summarizes the primary safety endpoint analysis and provides imputations for the safety population, indicating a rate between 2.0% and 14.7% for a best case and worst case scenario..

Table 9: Primary Safety Endpoint: Incidence of Device and/or Procedure Related, Clavien-Dindo Grade III or higher, through 52 Weeks.

| Analysis Population | Weeks | Incidence Rate | Upper Limit of 1-sided 95% CI* |
|--------------------------|-------|------------------|--------------------------------|
| Completers | 52 | 3 / 131 (2.3%) | 6.5% |
| Imputation (Best Case) | 52 | 3 / 150 (2.0%) | 5.7% |
| Imputation (Worst Case)^ | 52 | 22 / 150 (14.7%) | 21.4% |

^ Worst case scenario assumed that subjects with missing data had a safety endpoint event. Subjects that continue in active follow-up and have completed their 24-week visit were not reported as an SAE in Worst Case as all reported SAEs occurred prior to the 12 week visit. This ensures that continue to be followed but are not yet due for their expected visits do not negatively impact the imputation.

* Confidence interval was obtained based on the Agresti-Caffo confidence interval method, without multiplicity adjustment made.

The three adverse events rated Clavien-Dindo Grade III or higher were as follows:

- . One patient presented with an abdominal abscess and plural effusion two weeks after ESG.
- One patient was admitted at 11 weeks following ESG with weakness, dehydration, . altered mental status and was suspected of malnutrition.
- One patient was kept in the hospital after the ESG due to abdominal pain, nausea and . vomiting. It was determined that this patient had bleeding associated with the use of

⁴ Dindo, D., Demartines, N., & Clavien, P. A. (2004), Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Annals of surgery, 240(2), 205.

{18}------------------------------------------------

argon plasma coagulation to mark the intended suture locations. This patient was found to have clotted blood, which was located in the cardia (between the stomach and esophagus).

All three cases resolved with medical intervention.

An additional safety analysis was performed for the rate of serious adverse events (SAEs: Table 10). There were 21 device or procedure related SAEs reported from 11 of the 150 subjects receiving ESG (including primary and cross-over subjects). This an SAE rate of 7.3% (11/150: 95% CI: 3.7-12.7%). See Error! Reference source not found.. The most frequently reported SAEs were nausea, abdominal pain and vomiting. Seven patients were hospitalized after the ESG procedure to address early post-operative symptoms associated with accommodation to the sleeve, primarily nausea and yomiting. Treatments consisted of intravenous fluids, pain medications and anti-emetics and all adverse events resolved prior to discharge. There was also a device-related SAE during a cross-over ESG procedure that resulted in a mucosal tear in the esophagus and the decision was made to not complete the procedure. The patient was kept in the hospital for three days and then discharged.

| Serious Adverse Event¹ | # Subjects (%) | # Events | Onset (days to event) |
|-------------------------------------------------|------------------|----------|-----------------------------------------|
| Abdominal Abscess | 1/150 (0.7%) | 1 | 15 |
| Abdominal Pain | 3/150 (2.0%) | 3 | Mean = 1.7<br>Median = 2<br>Range = 0-3 |
| Bloody Stools | 1/150 (0.7%) | 1 | 0 |
| Bowel Impaction | 1/150 (0.7%) | 1 | 81 |
| Dehydration | 1/150 (0.7%) | 1 | 5 |
| Esophageal Mucosal Tear | 1/150 (0.7%) | 1 | 0 |
| GI bleeding at argon plasma<br>coagulation site | 1/150 (0.7%) | 1 | 0 |
| Malnutrition² | 1/150 (0.7%) | 1 | 77 |
| Nausea | 5/150 (3.3%) | 5 | Mean = 0.8<br>Median = 1<br>Range = 0-2 |
| Pleural Effusion | 1/150 (0.7%) | 1 | 20 |
| Pneumonitis | 1/150 (0.7%) | 1 | 4 |
| Sore Throat | 1/150 (0.7%) | 1 | 8 |
| Vomiting | 3/150 (2.0%) | 3 | Mean = 0.3<br>Median = 0<br>Range = 0-1 |
| Total | 11/150<br>(7.3%) | 21 | Mean = 11<br>Median = 2<br>Range = 0-81 |

Table 10:Device and/or Procedure Related Serious Adverse Events

1 A serious adverse event is one that:

- Led to death .
- Resulted in serious deterioration in the health of the subjects that results in: .
- Life-threatening illness or injury o
- Permanent impairment of a body structure or a body function o
- 0 The need for in-patient care or prolongation of hospitalization (this does not include the optional 23 hours observation admission after ESG or re-tightening procedure)

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- Medical or surgical intervention to prevent life-threatening illness or injury or permanent 0 impairment to a body structure or a body function
- Planned hospitalization for a pre-existing condition, or a procedure required by the trial protocol, without . serious deterioration in health, is not considered a serious adverse event
- 2 This patient that had their ESG reversed during the study.

Considering gastrointestinal adverse events that could be attributed to the device or procedure, the most common events were nausea, abdominal pain, constipation, heartburn and diarrhea (Table 11). These types of events tended to initiate within the first week of the procedure and to resolve within 30-60 days.

Table 11:Gastrointestinal Device and/or Procedure Related Adverse Events Occurring in > 10% of Subjects

| Adverse<br>Event | # Subjects<br>(%)<br>N=150 | Date of<br>Onset:<br>Median<br>(Mean)<br>Range | Duration in<br>Days¹:<br>Median<br>(Mean)<br>Range | Severity²<br>n/N (%):<br>Mild³<br>Moderate⁴<br>Severe⁵<br>Unknown⁶ | # Subjects<br>with onset<br><= 3 days<br>post-<br>procedure<br>(%) | # Subjects<br>with onset<br><= 3 post-<br>procedure<br>with<br>duration ><br>14 days and<br><= 30 days<br>(%) | # Subjects<br>with onset<br><= day 3<br>post-<br>procedure<br>with<br>duration ><br>30 days<br>(%) |
|--------------------|----------------------------|------------------------------------------------|----------------------------------------------------|----------------------------------------------------------------------|--------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|
| Nausea | 105<br>(70.0%) | 0<br>9.5<br>0-365 | 3<br>7.7<br>1-89 | 76/105<br>(72.4%)<br>24/105<br>(22.8%)<br>5/105 (4.8%) | 92/105<br>(87.6%) | 3/92<br>(3.3%) | 3/93<br>(3.3%) |
| Abdominal<br>Pain⁷ | 102<br>(68.0%) | 0<br>(37.5)<br>0-704 | 4<br>(16.1)<br>1-162 | 77/102<br>(75.5%)<br>22/102<br>(21.6%)<br>3/102 (2.9%)<br>0/102 (0%) | 82/102<br>(80.4%) | 8/82<br>(9.8%) | 6/82<br>(7.3%) |
| Eructation⁷ | 77<br>(51.3%) | 1<br>19.1<br>0-366 | 27<br>45.8<br>1-403 | 67/77<br>(87.0%)<br>10/77<br>(13.0%)<br>0/77 (0%)<br>0/77 (0%) | 55/77<br>(71.4%) | 5/55<br>(9.1%) | 24/55<br>(43.6%) |
| Vomiting | 74<br>(49.3%) | 0<br>23.5<br>0-541 | 2<br>8.1<br>1-368 | 54/74<br>(73.0%)<br>16/74<br>(21.6%)<br>3/74 (4.1%)<br>1/74 (1.3%) | 60/74<br>(81.1%) | 0/60<br>(0%) | 1/60<br>(1.7%) |
| Constipation⁷ | 68<br>(45.3%) | 7<br>39.5<br>0-567 | 26<br>51.5<br>1-368 | 51/68<br>(75.0%)<br>17/68<br>(25.0%)<br>0/68 (0%)<br>0/68 (0%) | 30/68<br>(44.1%) | 3/30<br>(10.0%) | 12/30<br>(40.0%) |

{20}------------------------------------------------

| Heartburn /<br>Reflux | 55<br>(36.7%) | 2<br>40.1<br>0-550 | 10<br>44.5<br>1-253 | 40/55<br>(72.7%)<br>14/55<br>(25.5%)<br>0/55 (0%)<br>1/55 (1.8%) | 34/55<br>(61.8%) | 4/34<br>(11.8%) | 9/34<br>(26.5%) |
|-----------------------|---------------|--------------------|---------------------|------------------------------------------------------------------|------------------|-----------------|-----------------|
| Diarrhea7 | 23<br>(15.3%) | 8<br>65.3<br>0-427 | 8<br>25.7<br>1-296 | 20/23<br>(87.0%)<br>2/23 (8.7%)<br>0/23 (0%)<br>1/23 (4.3%) | 9/23<br>(39.1%) | 1/9<br>(11.1%) | 1/9<br>(11.1%) |

1 Duration in Days = Date of Resolution - Date of Onset +1. Thus, an event that resolved the same day as onset will have a day of resolution = 1.

2 Subjects with multiple events of the same type are reported by first occurrence with the highest severity

3 Mild = awareness of sign or symptom, but easily tolerated, although not specifically defined in the study protocol 4 Moderate = discomfort enough to cause interference with usual activity, although not specifically defined in the study protocol

5 Severe = incapacitating with inability to work or do usual activity, although not specifically defined in the study protocol

6 Unknown = no response was recorded in the electronic database.

7 The following events did not have a resolution date recorded and were excluded from the durations (1 report of Abdominal pain, 3 reports of constipation, 1 report of diarrhea, and 1 report of eructation).

### Pediatric Extrapolation

In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.

## Real-World Evidence

Real-world evidence used to support a reasonable assurance of safety and effectiveness included real-world registry data and published clinical literature.

## Endoscopic sleeve gastroplasty (ESG)

A structured literature review was conducted to specifically identify all reported complications and adverse events that have been associated with ESG. Additionally, the literature review focused on the ability to perform revisions after ESG.

For the literature review, articles were retrieved from the PubMed database using the following search terms:

"endoscopic sleeve gastroplasty"[All Fields] OR "transoral outlet reduction"[All Fields] AND (("2017/01/01"[PDAT]: "3000/12/31"[PDAT]) AND "humans"]MeSH Terms] AND English[lang])

Duplicate articles were removed. A total of 51 articles were retrieved. Any publications that did not have sufficient information to be able to undertake a rational and objective assessment based on the appraisal of the full text article was not included in the clinical data analysis review; however, a review of the articles for safety data/incidents was performed. Inclusion is on criteria for article screening are outlined below:

Inclusion

- Describes endoscopic sleeve gastroplasty or transoral outlet reduction .

{21}------------------------------------------------

- . OverStitch device
Exclusion

- Review articles that do not include clinical data .
- . Editorial articles

Nine additional articles were considered due to their relevance though they were not recovered via the PubMed search. 5,6,7,8,9,10,11,12,13

The literature review supplements data from the MERIT Trial and supports the following statements.

- . Common adverse events tend to happen early after the procedure, and tend to resolve.
- Clinically meaningful weight loss can be achieved via the ESG procedure. .
- . An ESG procedure can be reversed in cases where the patient cannot tolerate the sleeve.
- . An ESG can be re-tightened in cases where the patient starts to regain weight after an initially successful result.
- An ESG can be revised to a laparoscopic sleeve gastrectomy (LSG) when needed. .
- ESG can be performed to tighten a sleeve from (LSG). .
- ESG may be performed in patients with BMI up to 50 kg/m2. .
- 0 There is durability to the weight loss achieved following the ESG procedure.

⁵ Alhayo S & Devadas M. Case Report: Laparoscopic sleeve gastrectomy following multiple failed endoscopic sleeve gastroplasties. J Surgical Case Reports 2019:12, 1-3.

⁶ Alqahtani A & Aljohani E. Case Report: Unusual presentation following endoscopic gastroplasty case report. J Surgical Case Reports 2020;7, 1-3.

⁷ Boskoski I, Pontecorvi V, Gallo C, Bove V, Laterza L, Costamagna G, Redo endoscopic sleeve gastroplasty: technical aspects and short-term outcomes. Therap Adv Gastroenterol. 2020 Jan 20;13:17562819896179. Doi: 10.1177/1756284819896179. eCollection 2020.

⁸ Cheng Q. Tree K. Edye M. Devadas M. Reversal of endoscopic sleeve gastroplasty and conversion to sleeve gastrectomy - Two case reports. Int J Surg Case Rep. 2020:68:180-184. Doi: 10.1016/j.ijscr.2020.02/060. Epub 2020 Feb 29.

⁹ Eid G. Sleeve gastrectomy revision by endoluminal sleeve plication gastroplasty: a small pilot case series. Surg Endosc. 2017 Oct:31(10):4252-4255. doi: 10.1007/s00464-017-5469-1. Epub 2017 Mar 31.

¹⁰ Espinet-Coll E. Nebreda-Durán J. Galvao-Neto M. Bautista-Altamirano C. Diaz-Galán P. Gómez-Valero JA. Vila-Lolo C, Guirola-Puche MA, Fernández- Huélamo A, Bargalló-Carulla D, Comamala AJ-C, Suture pattern does not influence outcomes of endoscopic sleeve gastroplasty in obese patients. Endosc Int Open. 2020 Oct;8(10):E1349-E1358. Doi: 10.1055/a-1221-9835. Epub 2020 Sep 22.

¹¹ Lopez-Nava G, et al., Biliary peritonitis after endoscopic sutured gastroplasty for morbid obesity (with video), Gastrointest Endoscopy 90:4 (2019), p686-688.

¹² Mohan BP. Asokkumar R. Khan SR. Kotagiri R. Sridharan GK. Chandan S. Ravikumar NP. Ponnada S. Javaraj M. Adler DG, Outcomes of endoscopic sleeve gastroplasty; how does it compare to laparoscopic sleeve gastrectomy? A systematic review and meta-analysis. Endose Int Open. 2020 Apr.8(4): E558-E565. Doi: 10.1055/a-1120-8350. Epub 2020 Mar 23.

¹³ Sharaiha RZ, Hajifathalian K, Kumar R, Saunders K, Mehta A, Ang B, Skaf D, Shah S, Herr A, Igel L, Dawod Q, Dawod E. Sampath K. Carr-Locke D. Brown R. Cohen D. Dannenberg A. Mahadev S. Shukla A. Aronne LF. Five-Year Outcomes of Endoscopic Sleeve Gastroplasty for the Treatment of Obesity, Clin Gastroenterol Hepatol. 2021 May;19(5):1051-1057.e2. doi: 10.1016/.cgh.2020.09.055. Epub 2020. Oct 1.

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The meta-analysis data are consistent with the experience in a registry conducted by the American Gastroenterological Society and other registry data.…