FDA Grants Fast Track Designation to FOG-001 for Desmoid Tumors – OncLive

Report on FOG-001 Fast Track Designation for Desmoid Tumors and Alignment with Sustainable Development Goals

Executive Summary

The United States Food and Drug Administration (FDA) has granted Fast Track designation to FOG-001, an investigational therapeutic for patients with desmoid tumors. This development represents a significant advancement in oncological research, directly contributing to the United Nations Sustainable Development Goal 3 (SDG 3), which aims to ensure healthy lives and promote well-being for all at all ages. FOG-001 is a first-in-class helicon peptide designed as a direct inhibitor of the β-catenin:T-cell factor (TCF) interaction, a core component of the Wnt signaling pathway implicated in the pathogenesis of these tumors.

Clinical Efficacy and Safety Profile

Data from the ongoing Phase 1/2 trial (NCT05919264) underscores the potential of FOG-001 to address a critical unmet medical need, aligning with SDG 3’s target to reduce premature mortality from non-communicable diseases through effective treatment.

• Efficacy in Desmoid Tumors:
  1. A 100% disease control rate (DCR) was observed in the 10 response-evaluable patients who had at least one post-baseline scan.
  2. An 80% overall response rate (ORR) was achieved in the subset of 5 patients who underwent more than one post-baseline scan.
  3. Positive responses were noted in patients regardless of prior exposure to gamma-secretase inhibitors.
• Safety and Tolerability:
  1. 83.3% of patients experienced at least one any-grade treatment-related adverse effect (TRAE).
  2. The rate of Grade 3 or higher TRAEs was 16.7%.
  3. Common TRAEs included fatigue, alopecia, and elevated liver enzymes.
  4. Importantly, no treatment discontinuations occurred due to TRAEs.

Phase 1/2 Trial Protocol

The multicenter, open-label Phase 1/2 study is evaluating FOG-001 in patients with locally advanced or metastatic solid tumors characterized by Wnt pathway activating mutations. The trial’s design and objectives are foundational to achieving SDG 3 by supporting the research and development of new medicines.

• Patient Population: The study includes cohorts for adult patients (≥18 years) with desmoid tumors, requiring an ECOG performance status of 0 or 1 and adequate organ function.
• Exclusion Criteria: Key exclusions include patients with certain bone metastases, osteoporosis, uncontrolled inflammatory bowel disease, and unstable brain metastases.
• Administration: FOG-001 is administered intravenously in continuous 28-day cycles for the desmoid tumor cohorts.
• Endpoints:
  • Primary Endpoints: Safety, incidence of dose-limiting toxicities, ORR, and DCR.
  • Secondary Endpoints: Pharmacokinetics, duration of response, and progression-free survival.

Alignment with Sustainable Development Goals (SDGs)

The development of FOG-001 is directly aligned with key targets of the UN Sustainable Development Goals, particularly SDG 3: Good Health and Well-being.

• SDG Target 3.4: By 2030, reduce by one-third premature mortality from non-communicable diseases through prevention and treatment. FOG-001 offers a novel therapeutic approach for desmoid tumors, a rare non-communicable disease with limited effective treatment options, thereby contributing to improved health outcomes and quality of life for patients.
• SDG Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries. The innovation behind FOG-001, which targets a previously “undruggable” pathway, exemplifies the critical research needed to create transformative medicines. This progress supports the global effort to develop new therapies for complex diseases.

By advancing a novel treatment that addresses the underlying biology of desmoid tumors, Parabilis Medicines’ work on FOG-001 reinforces the global commitment to fostering scientific innovation for public health, a central tenet of the Sustainable Development Goals.

Analysis of the Article in Relation to Sustainable Development Goals

1. Which SDGs are addressed or connected to the issues highlighted in the article?

• SDG 3: Good Health and Well-being: The article’s entire focus is on the development and clinical trial of a new drug, FOG-001, designed to treat desmoid tumors, a type of cancer. This directly relates to ensuring healthy lives and promoting well-being by advancing medical treatment for a non-communicable disease.

2. What specific targets under those SDGs can be identified based on the article’s content?

SDG 3: Good Health and Well-being

• Target 3.4: “By 2030, reduce by one-third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.” The development of FOG-001 is a direct effort to improve the “treatment” of a non-communicable disease (desmoid tumors). The article highlights its potential to “offer meaningful clinical benefit to patients” and intervene “at the source of disease,” contributing to better management and outcomes for this condition.
• Target 3.b: “Support the research and development of vaccines and medicines for the communicable and non-communicable diseases…” The article is a clear example of this target in action. It details the research and development of a novel drug (“the first direct inhibitor of the β-catenin:TCF interaction”), its progression through a phase 1/2 clinical trial (NCT05919264), and the support it has received, such as the FDA’s “fast track designation,” which accelerates the development process.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Indicators for Target 3.4 (Treatment of NCDs)

• Disease Control Rate (DCR): The article explicitly states that FOG-001 generated a “DCR of 100%” in the evaluated patient group. This is a direct measure of the treatment’s effectiveness in managing the disease.
• Overall Response Rate (ORR): The trial reported an “ORR of 80%” in patients who had more than one post-baseline scan. This indicator measures the percentage of patients whose tumors shrink by a specified amount, quantifying the positive impact of the treatment.
• Progression-Free Survival (PFS): Mentioned as a secondary endpoint of the clinical trial, PFS measures the length of time during and after treatment that a patient lives with the disease but it does not get worse. This is a key metric for evaluating the success of a cancer treatment.
• Duration of Response (DoR): Also listed as a secondary endpoint, this indicator measures how long the treatment continues to be effective in patients who have responded to it.

Indicators for Target 3.b (Research and Development)

• Regulatory Approval and Designation: The article states that the “FDA has granted fast track designation to FOG-001.” This is a specific, measurable milestone that indicates regulatory support for and acceleration of the R&D process for a promising new medicine.
• Progression of Clinical Trials: The article details the design and preliminary results of a “phase 1/2 trial (NCT05919264).” The existence and advancement of clinical trials for new therapies serve as a direct indicator of ongoing R&D activities.
• Development of First-in-Class Therapies: FOG-001 is described as the “first and only direct inhibitor of the β-catenin:TCF interaction.” The creation of such novel therapeutic approaches is a qualitative indicator of successful and innovative R&D.

4. Table of SDGs, Targets, and Indicators

Source: onclive.com