AlphaMedix Phase 2 Data Shows Potential in Gastroenteropancreatic Neuroendocrine Tumors
Breakthrough Clinical Results
AlphaMedix phase 2 study (ALPHAMEDIX-02) evaluating AlphaMedix (212Pb-DOTAMTATE) in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) showed clinically meaningful responses across both RLT-naïve and RLT-exposed patients. The study met all primary efficacy endpoints and was presented at the 2025 ESMO Congress. AlphaMedix is an investigational somatostatin receptor (SSTR) targeted alpha therapy (TAT) using the lead-212 isotope. The results support the potential of AlphaMedix as a first-in-class treatment for this difficult-to-treat cancer. An international phase 3 study is being planned.
Key Highlights
- AlphaMedix showed sustained and clinically meaningful responses in GEP-NET patients.
- Phase 2 study met all primary efficacy endpoints.
- AlphaMedix has potential as a first-in-class targeted alpha therapy.
- FDA granted AlphaMedix breakthrough therapy designation in RLT-naïve patients.
Incidence and Prevalence
Global Incidence and Prevalence of Gastroenteropancreatic Neuroendocrine Tumors
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a group of very heterogeneous neoplasms which are considered 'rare diseases'. Despite their perceived rarity, GEP-NETs are rising in incidence and prevalence globally.
Global Trends
Epidemiological studies on the incidence of GEP-NETs worldwide have reported a remarkable increase in the detection of these tumors. The incidences of GEP-NETs have increased in the Western countries as well as in Asia for years. Recent studies from the United States and Europe demonstrate an increasing GEP-NETs incidence.
Regional Data
Europe
A study based on pathology reports (PALGA) investigating the incidence of pancreatic and duodenal neuroendocrine tumors in the Netherlands from 1991 until 2009 noticed a significant increase in the incidence of these tumors. In particular, the incidence of non-functioning neuroendocrine tumors had significantly increased over this period.
Asia
In a 2017 study from West China, GEP-NETs proportion increased 1.6-fold during a 5-year period from 1.28/10^5 to 2.03/10^5. The most common sites were rectum (30.6%), pancreas (23.4%), gastric (13.3%), and esophagus (11.3%).
Middle East
A 2021 Turkish study of 128 patients with GEP-NETs found that the most common site was stomach (36.7%), with 40.9% diagnosed at stage 4. The 3- and 5-year overall survival rates were 78% and 69%, respectively.
A Saudi Arabian study noted that 54.2% of patients were metastatic at diagnosis, which was described as "a higher incidence of metastatic disease at presentation than in the rest of the world."
India
Limited data is available on epidemiology in India. A 2010 analysis of 74 patients showed the most common tumor site was stomach (30.2%), followed by pancreas (23.3%) and duodenum (18.9%).
Global Patient Characteristics
A 2022 study of 662 patients from Europe, Asia, and South America found a mean age of 62 years with 53.9% being male. The most common stage was stage IV (85%) with liver metastases (89.0%) representing the most common site of extra-pancreatic tumor manifestation. At time of diagnosis, 93.1% of patients were classified as inoperable.
Specific Tumor Types
Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms accounting for less than 5% of all pancreatic malignancies. Approximately half of the patients with pancreatic neuroendocrine tumors harbored liver metastasis when initially diagnosed, whose prognosis is dismal.
Neuroendocrine tumors of the ampulla of Vater are extremely uncommon, accounting for only about 0.3%-1% of all gastrointestinal neuroendocrine tumors, with approximately 139 cases reported to date.
The vast majority of GEP-NETs are well differentiated and slowly growing with only a minority showing aggressive behavior. In general, NETs are slow-growing neoplasms and the data on the natural history is still evolving.
A 2018 study noted that "the pattern of gastrointestinal neuroendocrine tumors has definitely changed over last few years," highlighting the dynamic nature of this disease's epidemiology.
Key Unmet Needs for Gastroenteropancreatic Neuroendocrine Tumors
Diagnostic Challenges
- Accurate staging remains crucial for implementing correct treatment and improving prognosis
- Novel imaging modalities are being evaluated to increase sensitivity for detecting micro-metastases
- Ga-DOTATATE PET/CT is highly sensitive but its clinical impact for post-treatment surveillance remains unclear
- The NETest shows promise as a biomarker with >90% accuracy but has low specificity due to interference with other gastrointestinal malignancies
Treatment Optimization
- Limited therapeutic options in both quantity and durability of benefit for advanced/metastatic GEP-NETs
- Comparison between therapeutic modalities is difficult, warranting further studies to individualize treatment
- Targeted alpha therapy (TAT) with Ac-DOTATATE shows promise for patients with SSTR-expressing advanced-stage metastatic GEP-NETs
- Peptide receptor radionuclide therapy (PRRT) clinical trials are scarce, with approximately 30% of patients experiencing disease progression
- Treatment recommendations for well-differentiated G3 tumors lack strong scientific evidence, with most studies being retrospective
Specific Patient Populations with Unmet Needs
- Patients with Lu-PRRT-refractory disease show poorer outcomes even with newer therapies
- Patients with bone metastases have been identified as having poorer overall survival
- High tumor growth rate (TGR) tumors (primarily G3 pancreatic NETs) exhibit decreased time to first therapy and shorter survival
- Patients with previously undiagnosed grade progression could benefit from TGR as a noninvasive identification method
- Advanced grade 2-3 well-differentiated NETs and grade 3 neuroendocrine carcinomas after progression on prior therapies
Future Research Directions
- Identification of effective therapeutic strategies for advanced and metastatic patients is a high priority
- Defining optimal schedules for integrating targeted agents with conventional cytotoxics and other treatment options
- Identifying appropriate biomarkers for patients with potential to derive greater benefit from treatments
- Advances in tumor biology, genetics, immunology, nanotechnology, and radiation pharmacology should expand targeted therapies
- Clinical trials may benefit from stratification for TGR, particularly in G1-2 tumors
- Evaluation of HRAS expression in tumor tissue might improve patient selection for lenvatinib treatment
- Further development of lenvatinib in advanced NETs is warranted based on demonstrated efficacy
- Research on lifestyle influences on disease progression and treatment response
- Mechanisms of resistance to primary systemic therapeutic options including somatostatin analogues, PRRT, everolimus, sunitinib, and temozolomide-based chemotherapy
Company drugs in pipeline
Orano Med's Drug Pipeline Indications
Based on a thorough review of available information, there is insufficient data to provide details about Orano Med's drug pipeline. The current information does not specify which indications Orano Med has drugs in development for, nor does it outline any specific therapeutic areas or cancer indications that might be targeted by their pharmaceutical development efforts.
Without confirmed information, it would be inappropriate to speculate about Orano Med's clinical programs, development stages, or targeted diseases. The pharmaceutical pipeline of any company represents its future potential and strategic direction, but no verifiable details about Orano Med's specific drug candidates or their clinical trial phases are currently available in the reviewed materials.
For accurate and up-to-date information about Orano Med's drug development programs, interested parties should consult the company's official website, recent press releases, investor presentations, or regulatory filings which would contain the most current details about their therapeutic focus and pipeline assets.
