Acasti Pharma (ACST) is a late-stage specialty biotech developing novel therapies for rare diseases, specifically for those who are underserved or lack treatment options.
GTX-104
ACST’s lead program, GTX-104, is a room-temperature stable, IV formulation of nimodipine that targets aneurysmal subarachnoid hemorrhage (aSAH), a life-threatening condition where bleeding occurs over the surface of the brain due to an aneurysm rupture. GTX-104’s novelty is that it is designed for continuous IV infusion of nimodipine, allowing better absorption and easier administration than existing standard of care, an oral administration of nimodipine.
In a Type C meeting response, the FDA agreed with the use of the 505(b)(2) regulatory pathway for GTX-104. This pathway allows Acasti to leverage existing data from nimodipine (brand: Nimotop) oral capsules (NDA 018869) while supplementing it with their pharmacokinetic (PK) bridging study, which the FDA acknowledged as meeting the criteria for a scientific bridge. With this pathway, GTX-104 aims for expedited approval, pending successful Phase 3 results and submission of the New Drug Application (NDA).
A Section 505(b)(2) application includes comprehensive reports on safety and efficacy studies. However, some of the required approval data is derived from research not performed by or on behalf of the applicant, and the applicant lacks the right of reference for these studies.
ACST’s clinical progression for GTX-104 is largely de-risked. The company has already completed multiple Phase 1 trials head-to-head IV versus the oral dosage form of nimodipine, establishing bioequivalence between GTX-104 and the oral. This points to the potential for extreme asymmetry in risk/reward given the company’s current valuation equivalent to its cash balance.
GTX-104 has received Orphan Drug Designation (ODD) from the FDA for the treatment aSAH. This designation provides several incentives and benefits to encourage the development of treatments for rare diseases, including:
- Market Exclusivity: Seven years of market exclusivity after approval, protecting GTX-104 from direct competition in treating SAH.
- Tax Credits: Tax credits to offset some of the research and development costs.
- Fee Waivers: Waivers or reductions in application fees, such as those associated with NDAs.
- Regulatory Support: Additional regulatory assistance and guidance during the drug development process.
By granting GTX-104 this designation, the FDA recognizes the significant unmet need in treating aSAH and the potential impact this novel therapy could have in improving patient outcomes.
Key aspects of the pivotal Phase 3 study:
- Design: It was an open-label, randomized crossover study involving healthy adult volunteers;
- Objective: The primary goal was to characterize the PK profile of GTX-104, comparing it to existing forms of nimodipine administration;
- Dosing and Bioavailability: Different dosing levels were used to determine the linearity, absorption, and consistency of the drug’s concentration in the blood.
- Results: The study demonstrated that GTX-104 had a more predictable; absorption pattern, with better dose proportionality than oral nimodipine. This formulation was found to have favorable bioavailability for managing aSAH complications
- Simple trial design and primary endpoint: safety measured by comparative AEs.
IP
ACST’s intellectual property portfolio consists of more than 40 granted and pending patents in various jurisdictions worldwide. The company states that its earliest patent expiration will not occur until 2037.
Cash
ACST’s has cash of about $25 million, sufficient to carry the company to Phase 3 readout in Q424. This is roughly equivalent to the company’s current market cap.
aSAH
aSAH is a critical form of stroke that occurs when an aneurysm—a weakened blood vessel—ruptures, causing bleeding in the subarachnoid space between the brain and its surrounding membranes. This sudden bleeding can lead to increased intracranial pressure, brain injury, and potentially fatal complications such as vasospasm (constriction of blood vessels). Symptoms of aSAH often include a sudden and severe headache, nausea, vomiting, and neck stiffness. Immediate medical intervention is essential to reduce mortality and long-term disabilities. Two thirds of patients either do not survive or are left severely debilitated. aSAH patients often cannot take a pill as the GI tract is impaired or shut down.
GTX-104 targets the core issues of aSAH by providing nimodipine, a calcium channel blocker that helps reduce vasospasm and manage hypotension, the primary complications of aSAH. Compared to oral nimodipine, GTX-104 provides the following advantages:
- Enhanced Absorption: Oral nimodipine has limited and inconsistent absorption when administered through the gastrointestinal tract, especially in unconscious patients. GTX-104 provides a more consistent delivery through an IV infusion, bypassing these challenges.
- Improved Control: IV administration allows for precise dosing adjustments, ensuring better control of the drug’s effects on blood pressure and cerebral blood flow. This can help prevent death and reduce long-term disability in aSAH patients.
- Faster Response: Continuous IV infusion enables faster onset and more predictable therapeutic effects compared to oral administration, potentially improving outcomes in critical early management
These advantages offer much improved administration for patients who are typically in an ICU setting and much lower cost stemming from precise dosing adjustments. As such, distribution and sales upon approval will be a far easier task because physicians and hospitals are already familiar with nimodipine.
TAM
The U.S. market has a potential of at least $350-$500 million annually, given 50,000 annual cases of aSAH. Pricing would likely be $500-$750/day for an average hospital stay of 14 days.
The following have been shelved until the outcome of GTX-104:
GTX-102
GTX-102 is an oral spray formulation of betamethasone which aims to improve symptoms of ataxia-telangiectasia (A-T), a neurodegenerative disease primarily affecting children. The spray is designed for ease of administration and has shown promising results in pharmacokinetic studies. Currently, no FDA-approved treatments exist for A-T, creating a market opportunity of around $150 million in the U.S.
GTX-101
GTX-101 was developed as a topical spray of bupivacaine, GTX-101 which aims to treat postherpetic neuralgia (PHN), a persistent neuropathic pain following shingles. The bio-adhesive spray can provide quicker and longer-lasting pain relief than current treatments like lidocaine patches and oral medications. The potential U.S. market for this therapy is estimated at $200 million, addressing 130,000 patients per year.
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