The FDA has granted Orphan Drug Designation to two investigational therapies, ABD-147 and PT217, for the treatment of neuroendocrine carcinoma (NEC), a rare cancer affecting hormone-producing cells. These designations aim to incentivize the development of treatments for diseases affecting fewer than 200,000 people in the United States.
ABD-147: Targeted Radiopharmaceutical Therapy
ABD-147, developed by Abdera Therapeutics, is a next-generation precision radiopharmaceutical biologic therapy designed to deliver the radioisotope Actinium-225 to tumors expressing DLL3 (Delta-Like Ligand 3). DLL3 is upregulated in some high-grade neuroendocrine carcinomas, including small cell lung cancer (SCLC), while typically absent on nonmalignant cells, making it an attractive target for radiotherapy. The FDA previously granted Fast Track designation to ABD-147 for extensive-stage SCLC in July 2024.
Philippe Bishop, MD, chief medical officer of Abdera Therapeutics, stated that neuroendocrine carcinomas, including SCLC and large cell neuroendocrine carcinoma (LCNEC), are aggressive and challenging to treat effectively with current systemic therapies. He believes ABD-147 has the potential to become a best-in-class DLL3-targeting treatment for aggressive neuroendocrine tumors by delivering a potent radioisotope to neuroendocrine tumors expressing DLL3 with custom-engineered pharmacokinetic properties.
Abdera Therapeutics plans to initiate a phase 1, first-in-human study to evaluate ABD-147 in patients with SCLC or LCNEC who have previously received platinum-based therapy.
The Orphan Drug Designation provides Abdera Therapeutics with incentives such as tax credits for clinical trials, exemption from user fees, and a potential seven years of market exclusivity if ABD-147 is approved.
PT217: Bispecific Antibody Targeting DLL3 and CD47
PT217, developed by Phanes Therapeutics, is a first-in-class bispecific antibody targeting delta-like ligand 3 (DLL3) and cluster of differentiation 47 (CD47). It had previously received Orphan Drug Designation for SCLC in 2022 and Fast Track designation in 2024 for extensive-stage SCLC with disease progression following platinum chemotherapy with or without checkpoint inhibitors. PT217 will also be investigated in combination with atezolizumab.
Phanes Therapeutics is planning to study PT217 in the SKYBRIDGE trial (NCT05652686), a phase 1/2, open-label, dose-escalation and expansion study. The trial will assess the safety, tolerability, pharmacodynamics, and preliminary efficacy of PT217 in patients with NEC, including SCLC, LCNEC of the lung, and extrapulmonary neuroendocrine carcinoma (EP-NEC). Eligible patients must have progressed after standard therapy or found standard therapy to be ineffective, intolerable, or inappropriate.
The SKYBRIDGE trial employs a 3+3 dose escalation design, starting with PT217 at 0.2 mg/kg weekly and escalating to provisional dose levels of 0.6 mg/kg, 2 mg/kg, 6 mg/kg, and 12 mg/kg weekly. The primary endpoints include determining the dose-limiting toxicity, maximum tolerated dose, recommended phase 2 dose, and safety of PT217. Secondary outcomes include objective response rate, disease control rate, progression-free survival, 6-month overall survival, and pharmacokinetic parameters.
With an estimated 12,000 individuals in the US diagnosed with neuroendocrine tumors each year, the development of new therapies like ABD-147 and PT217 offers hope for improved treatment options for this challenging disease.
