NEI Project on Effect of AMTN Inhibitor Drugs on AMD Progression

The National Institutes of Health (NIH) intends to award a Firm-Fixed-Price purchase order to Kaiser Permanente to identify potential new therapeutic use of drugs approved for other conditions to slow AMD progression.

In accordance with FAR Part 6.302-1, the Contractor is the only known responsible source who can provide the specific services per SOW below. This notice is not a request for competitive quotes. However, any party that believes it can provide the services as stated herein may submit a written capability statement that clearly supports and demonstrates their ability to satisfy the requirement. A determination by the Government to compete this proposed award based upon responses to this notice is solely within the discretion of the Government. It is anticipated that an award will be issued approximately five (5) days after the date of this notice unless the Government determines that another organization has the capability to meet this requirement. Please email responses to Sharmaine.fagan@nih.gov no later than 08:00 a.m. EST on Thursday, August 10, 2023.

INTRODUCTION

1.1 BACKGROUND

Age-related macular degeneration (AMD) is a leading cause of vision loss in aging populations. There is currently no treatment for the dry form of AMD. This project aims to identify potential new therapeutic use of drugs approved for other conditions to slow AMD progression.

1.2 SCOPE AND OBJECTIVES

Progression of dry AMD is correlated with formation of hydroxyapatite (HAP) deposits at the back of the eye. The enamel protein amelotin (AMTN) is induced in dry AMD and plays a key role in HAP deposition. Several FDA approved drugs have been identified which inhibit HAP formation by AMTN. We want to determine what effect these drugs have on progression of dry AMD, with the hope of identifying treatments to slow vision loss. This requires analysis of patient databases covering use of drugs of interest and AMD status that are available at Kaiser Permanente.

2.0 REQUIREMENTS

2.1 TASKS AND DDELIVERABLES

Identify 30 cases of non-exudative and/or exudative age-related macular degeneration (AMD) with evidence of monitoring in both the period before and after the initial AMD diagnosis date (i.e., pre- index and post-index period). The index date is the earliest encounter date for an AMD diagnosis of interest. At least 12 months of continuous enrollment is required prior to, but not including the index date. The pre-index and post-index periods are defined as follows:

Pre-Index:

• • Start Date = the date of the first encounter (any diagnosis) during the continuous enrollment period
  • End Date = the day prior to the index date Post-Index:
  • Start Date = Index date (AMD diagnosis date)
  • End Date = the date of the last encounter (any diagnosis) during the continuous enrollment period

For each of the 30 cases:

1. Determine/confirm the sequencing/progression of AMD diagnosis (non-exudative to exudative AMD)
2. Subdivide the 30 cases into 3 exposure groups
   1. Evidence of montelukast or bisphosphonate exposure in the pre-index period (n=13)
   2. Evidence of montelukast or bisphosphonate exposure in the post-index period (n=6)
   3. Evidence of montelukast or bisphosphonate exposure in both periods (n=11)
3. Conduct a chart review and case series analysis of:
   1. Cases with pre-index exposure only
   2. Cases with post-index exposure only
   3. Cases with both pre- and post-index exposure
4. Chart review will include evaluation of electronic health record clinical encounter data, clinical examination results, retinal Optical Coherence Tomography (OCT) results, encounter notes, patient history, and pharmacy data.
5. Evidence of AMD progression defined by:
   1. Observation of drusen, calcium deposits
   2. Vision impairment and vision loss as evidenced by:
      1. Visual Acuity Test
      2. Visual Field Tests (including Amsler Grid)
      3. Pupil Response Test
   3. Visual Acuity Test Rod intercept time
   4. Dark adaptation times
   5. Initiation of AREDS / AREDS 2 Vitamins
   6. Initiation if intravitreal injections of Anti-VEGF Drugs
      1. Avastin (bevacizumab)
      2. Lucentis (ranibizumab)
      3. Eylea (aflibercept)
      4. Beovu (brolucizumab)
      5. Vabysmo (faricimab)
   7. Initiation of Photodynamic Therapy (PDT)
   8. Changes in diagnostic coding
6. Qualitatively compare/contrast and report observed findings.

2.2 SCHEDULE

Performance will be at the contractor's facility, The period of performance will be no more than one calendar year after contract award.

3.0 GOVERNMENT FURNISHED PROPERTY

List of candidate drugs identified as AMTN inhibitors has already been provided under a confidentiality agreement. Two widely used drugs from that list, montelukast or bisphosphonate, have been selected for analysis.

4.0 SECURITY REQUIREMENTS

None