Passage Bio Announces Positive Feedback from FDA on Expansion of upliFT-D Trial of PBFT02 to Include FTD-C9orf72 Patients

Rhea-AI Summary

Passage Bio (NASDAQ: PASG) has received positive feedback from the FDA on expanding its upliFT-D trial of PBFT02 to include FTD-C9orf72 patients. The company plans to amend the ongoing Phase 1/2 global study protocol to introduce this new patient population, with dosing expected to begin in 1H 2025. This expansion is supported by compelling preclinical evidence and safety data from the first cohort of FTD-GRN patients treated with PBFT02.

FTD-C9orf72 affects approximately 21,000 individuals in the US and Europe. The FDA has granted PBFT02 Fast Track and Orphan Drug designations, while the European Commission has also given it Orphan designation. This development could bring new hope to an underserved patient community with clinical trial options.

Positive

• FDA alignment on expanding upliFT-D trial to include FTD-C9orf72 patients
• Potential to address an unmet need for 21,000 FTD-C9orf72 patients in US and Europe
• Fast Track and Orphan Drug designations from FDA for PBFT02
• Orphan designation from European Commission for PBFT02
• Encouraging safety and PGRN expression data from first cohort of FTD-GRN patients

Negative

• Dosing of FTD-C9orf72 patients not expected to begin until 1H 2025

Insights

Medical Research Analyst

Passage Bio's recent FDA feedback is a noteworthy development for the company’s efforts to treat frontotemporal dementia (FTD) with mutations in the C9orf72 gene. This particular form of FTD is characterized by the abnormal accumulation of the TDP-43 protein in neurons, which leads to neurodegeneration. By targeting this mutation, Passage Bio aims to address a significant unfulfilled need in the medical community.

One important aspect here is the preclinical evidence that shows increasing levels of progranulin (PGRN) can mitigate TDP-43 pathology. Existing data from the upliFT-D trial with FTD-GRN patients provides a robust foundation for expanding the study to include FTD-C9orf72 patients. The promise shown in these initial results heightens the optimism surrounding PBFT02’s therapeutic potential.

For retail investors, it’s essential to recognize that the fast track and orphan drug designations from the FDA and European Commission confer certain benefits, including expedited review processes and potential market exclusivity. These advantages can accelerate PBFT02’s path to market, effectively reducing the time and cost of development.

However, it’s important to keep in mind that clinical trials carry inherent risks and uncertainties. Positive preclinical results may not always translate to clinical success. Investors should stay informed about the progress of the expanded trial and monitor any forthcoming data to make well-grounded decisions.

Financial Analyst

Expanding the upliFT-D trial to include FTD-C9orf72 patients could have a significant impact on Passage Bio's financial outlook. The FTD-C9orf72 population represents a sizable market opportunity, with approximately 21,000 affected individuals in the U.S. and Europe. Successfully addressing this unmet medical need could drive substantial revenue growth for the company.

The fact that PBFT02 has already received both Fast Track and Orphan Drug designations is financially beneficial. Fast Track designation facilitates more frequent interactions with the FDA, potentially leading to faster approval times. Orphan Drug designation can provide up to seven years of market exclusivity in the U.S. post-approval, which shields the drug from direct competition and can assure higher profitability margins.

While this news bodes well for Passage Bio’s long-term prospects, investors should remain cautious about the near-term financial implications. Clinical trials are costly and the inclusion of a new patient population will likely increase research and development expenses. The company’s ability to manage these costs effectively while progressing through clinical phases will be a critical factor to watch.

It’s also important to scrutinize the company’s cash reserves and funding strategies. Any delays or setbacks could necessitate additional financing rounds, potentially diluting existing shareholders.

Agency feedback from Type C meeting process supports the company's proposed clinical development plans to expand the upliFT-D trial to assess PBFT02 in FTD patients with C9orf72 gene mutations

Plan to initiate dosing of FTD-C9orf72 patients in 1H 2025

PHILADELPHIA, July 16, 2024 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a clinical-stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today announced that the company received positive feedback in its Type C meeting process with the U.S. Food and Drug Administration (FDA) on its proposal to evaluate PBFT02 for treating frontotemporal dementia (FTD) patients with mutations in the C9orf72 gene. Compelling preclinical evidence, coupled with available safety and robust progranulin (PGRN) expression data from the first cohort of FTD-GRN patients treated with PBFT02, supported FDA alignment on the proposed trial expansion. The company intends to amend the protocol for the ongoing upliFT-D Phase 1/2 global study for FTD-GRN to introduce a new population of FTD-C9orf72 patients.

"Securing FDA alignment on amending our upliFT-D protocol to include FTD-C9orf72 patients is a critical milestone in expanding access to those who could benefit from PBFT02,” said Will Chou, M.D., president and chief executive officer of Passage Bio. “Given the limited clinical trials for FTD-C9orf72 patients, we believe PBFT02 could fill a significant unmet need and bring new hope to this underserved patient community. We look forward to further advancing the clinical development of PBFT02 and building upon the encouraging data we’ve seen from the upliFT-D trial so far.”

FTD-C9orf72 is estimated to affect approximately 21,000 individuals in the United States and Europe. Similar to FTD-GRN, FTD-C9orf72 is marked by TDP-43 pathology, where the transactive response DNA binding protein 43 (TDP-43) abnormally accumulates in the cytoplasm of neurons, leading to neuronal dysfunction and degeneration. Third-party preclinical studies have demonstrated that increasing PGRN levels can reduce TDP-43 pathology and slow neurodegeneration.

The company plans to submit the revised trial protocol to health authorities and ethics committees promptly and expects to initiate dosing of FTD-C9orf72 patients in 1H 2025.

The FDA has granted PBFT02 Fast Track and Orphan Drug designations. PBFT02 has also received an Orphan designation from the European Commission.

About PBFT02

PBFT02 utilizes an AAV1 viral vector to deliver, through ICM administration, a functional GRN gene that encodes for progranulin (PGRN). This vector and delivery approach aims to elevate PGRN levels in the central nervous system (CNS) to alter the course of neurodegenerative diseases.

PBFT02 is supported by extensive preclinical studies indicating broad transduction across the brain, including high transduction of ependymal cells, and demonstrated robust increases in cerebrospinal fluid (CSF) PGRN concentrations. Robust CSF PGRN levels have also been observed clinically based on interim data.

About Passage Bio

Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines company on a mission to improve the lives of patients with neurodegenerative diseases. Our primary focus is the development and advancement of cutting-edge, one-time therapies designed to target the underlying pathology of these conditions. Passage Bio’s lead product candidate, PBFT02, seeks to treat neurodegenerative conditions, including frontotemporal dementia, by elevating progranulin levels to restore lysosomal function and slow disease progression.

To learn more about Passage Bio and our steadfast commitment to protecting patients and families against loss in neurodegenerative conditions, please visit: www.passagebio.com.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including the initiation of dosing of FTD-C9orf72 patients; the progress of clinical studies and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; and the ability of our product candidates to treat their respective target CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:
Stuart Henderson
Passage Bio
267.866.0114
shenderson@passagebio.com

Passage Bio Media:
Mike Beyer
Sam Brown Inc. Healthcare Communications
312.961.2502
mikebeyer@sambrown.com

FAQ

What is the latest development for Passage Bio's PBFT02 trial?

Passage Bio has received positive FDA feedback to expand its upliFT-D trial of PBFT02 to include FTD-C9orf72 patients, with plans to begin dosing this new patient group in the first half of 2025.

How many patients could potentially benefit from PBFT02 for FTD-C9orf72?

Approximately 21,000 individuals in the United States and Europe are estimated to be affected by FTD-C9orf72, representing a significant patient population that could potentially benefit from PBFT02.

What designations has PBFT02 received from regulatory authorities?

PBFT02 has received Fast Track and Orphan Drug designations from the FDA, as well as an Orphan designation from the European Commission.

When does Passage Bio (PASG) expect to start dosing FTD-C9orf72 patients with PBFT02?

Passage Bio plans to initiate dosing of FTD-C9orf72 patients with PBFT02 in the first half of 2025.

What evidence supports the expansion of the PBFT02 trial to FTD-C9orf72 patients?

The expansion is supported by compelling preclinical evidence and available safety and robust progranulin (PGRN) expression data from the first cohort of FTD-GRN patients treated with PBFT02.