pharma · Advanced Solid Tumor · Acute Myeloid Leukemia or Myelodysplastic Syndromes · APRE
Aprea Therapeutics is a pharma organization headquartered in Doylestown, USA. It trades on NYSE under ticker APRE. Primary therapeutic focus areas include Advanced Solid Tumor, Acute Myeloid Leukemia or Myelodysplastic S
Phase 3 · small molecule · MDS
APR-246 + azacitidine is a Phase 3 combination therapy developed by Aprea Therapeutics for myelodysplastic syndrome (MDS). The program pairs APR-246, a small-molecule investigational agent, with azacitidine, an established antineoplastic and immunomodulating agent administered orally. Azacitidine is approved across maj
Internal code A18-15331
APR-246 + azacitidine is a Phase 3 combination therapy developed by Aprea Therapeutics for myelodysplastic syndrome (MDS). The program pairs APR-246, a small-molecule investigational agent, with azacitidine, an established antineoplastic and immunomodulating agent administered orally. Azacitidine is approved across major markets including the United States, European Union, Australia, and China, with multiple generic and branded formulations available from manufacturers including Bristol-Myers Squibb, Accord Healthcare, and Dr Reddy's Laboratories.
The combination program is registered under internal code A18-15331 and is being evaluated in the pivotal trial NCT03745716. As of March 18, 2025, the program has completed Phase 3 development. The specific mechanism of action for APR-246 and its target are not yet disclosed. Azacitidine itself is classified as an antineoplastic and immunomodulating agent (ATC code L01) and is available as an oral formulation under multiple brand names including AZACITIDINE ACCORD.
The regulatory landscape shows azacitidine is well-established globally with approved status in Australia (PBS-listed since 2017), the European Union (multiple marketing authorizations from 2025-2026), and the United States (multiple ANDA and NDA approvals). In China, azacitidine remains in clinical trials across five active studies. The program's latest milestone occurred on March 18, 2025, though specific milestone details are not yet disclosed. Expected next milestones and projected peak sales figures have not been disclosed.
Myelodysplastic syndrome represents a significant unmet medical need, particularly in elderly and treatment-resistant patient populations. MDS is a group of clonal hematopoietic disorders characterized by dysplasia, cytopenia, and risk of progression to acute myeloid leukemia. Current standard-of-care therapies, including hypomethylating agents like azacitidine, demonstrate variable efficacy with many patients experiencing disease progression or relapse.
The combination of APR-246 with azacitidine addresses the clinical challenge of improving response rates and durability in MDS patients. Aprea's strategy focuses on combination therapy to potentially overcome resistance mechanisms and enhance therapeutic benefit. The market relevance is substantial given the aging population at risk for MDS and the limited options for patients who fail or are intolerant to existing therapies.
Competitive positioning against approved alternatives such as VYXEOS Liposomal (Jazz Pharmaceuticals) and other antineoplastic agents is relevant to MDS treatment algorithms. The patient population for MDS is estimated at tens of thousands annually in developed markets, with significant mortality and morbidity burden. Commercial significance is supported by the chronic nature of MDS treatment, potential for combination therapy adoption, and the established market for azacitidine-based regimens. Successful Phase 3 completion signals potential for regulatory filing and market entry, though specific efficacy and safety data from the pivotal trial remain undisclosed.
Drug Class: Combination antineoplastic therapy pairing APR-246 (investigational small-molecule) with azacitidine (established hypomethylating agent).
Modality: Small-molecule oral combination.
Route of Administration: Oral (azacitidine component confirmed as oral formulation).
Mechanism of Action: APR-246 mechanism not yet disclosed. Azacitidine functions as an antineoplastic and immunomodulating agent (ATC L01), with established hypomethylating activity in MDS.
Target: Not yet disclosed for APR-246 component.
Also known as: MDS, MDS, unclassifiable, MDS-U, Myelodysplastic Syndromes, dysmyelopoietic syndrome, hematopoeitic - myelodysplastic syndrome (MDS)
Prevalence: Point prevalence: 1-9 / 100 000 (Germany) — source: Orphanet, validated.
A clonal hematopoietic disorder characterized by dysplasia and ineffective hematopoiesis in one or more of the hematopoietic cell lines. The dysplasia may be accompanied by an increase in myeloblasts, but the number is less than 20%, which, according to the WHO guidelines, is the requisite threshold for the diagnosis of acute myeloid leukemia. It may occur de novo or as a result of exposure to alkylating agents and/or radiotherapy. (WHO, 2001)
ClinicalTrials.gov lists 102 registered studies for Myelodysplastic Syndrome (MDS) (AACT aggregate).
Phase breakdown: PHASE2 (41), PHASE1 (25), PHASE1/PHASE2 (18), NA (11), PHASE3 (5), EARLY_PHASE1 (1), PHASE4 (1)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0018881), Orphanet — myelodysplastic syndrome, NCT00145613, NCT00186823, NCT00225992, NCT00270452, NCT00280631, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
Phase 3 ongoing
APR-246 + azacitidine combination evaluated in pivotal trial NCT03745716 for MDS.
Phase 3 completed
Program completion milestone reached; specific results and regulatory implications not yet disclosed.
The MDS treatment landscape includes several approved antineoplastic agents identified in the competitive set. VYXEOS Liposomal (Jazz Pharmaceuticals Ireland Limited) represents a liposomal combination therapy approved for acute myeloid leukemia and MDS-related conditions. IMBRUVICA (Janssen-Cilag) is a Bruton tyrosine kinase inhibitor approved for hematologic malignancies. AFINITOR (Novartis Pharmaceuticals) is an mTOR inhibitor with oncology indications. INLYTA (Pfizer Australia) is a tyrosine kinase inhibitor. KYPROLIS (Amgen) is a proteasome inhibitor for multiple myeloma. OFEV (Boehringer Ingelheim) addresses idiopathic pulmonary fibrosis.
The APR-246 + azacitidine combination differentiates through dual-agent mechanism targeting MDS specifically. Azacitidine itself is widely available as generic and branded formulations from multiple manufacturers (Bristol-Myers Squibb, Accord Healthcare, Dr Reddy's, and others), establishing a competitive baseline. The addition of APR-246 aims to enhance efficacy beyond azacitidine monotherapy. Competitive positioning depends on Phase 3 efficacy, safety, and tolerability data relative to existing hypomethylating agent regimens and combination approaches. The competitive set listed does not include direct MDS-focused comparators, suggesting the program may address a differentiated niche within the broader antineoplastic market.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| PFIZER AUSTRALIA PTY LTD | Pfizer Australia Pty Ltd | — | approved |
| IMBRUVICA | Janssen-Cilag Pty Ltd | — | approved |
| AFINITOR | Novartis Pharmaceuticals | — | approved |
| LYSODREN | S.A. | — | approved |
| INLYTA | Pfizer Australia Pty Ltd | — | approved |
| LYNOZYFIC | Regeneron UK Limited | — | approved |
| VYXEOS LIPOSOMAL (PREVIOUSLY VYXEOS) | Jazz Pharmaceuticals Ireland Limited | — | approved |
| KYPROLIS | Amgen | — | approved |
| UNITUXIN | United Therapeutics Europe Ltd | — | approved |
| PACLITAXEL ACCORD | Accord Healthcare Pty. | — | approved |
| OFEV | Boehringer Ingelheim Pty Ltd | — | approved |
| ARX-IMATINIB | Alphapharm Pty Ltd | — | approved |
| LUSPATERCEPT | — | Transforming growth factor beta inhibitor | Approved |
| LENALIDOMIDE | — | CRL4(CRBN) E3 ubiquitin ligase inhibitor | Approved |
| DECITABINE | — | DNA (cytosine-5)-methyltransferase 1 inhibitor | Approved |
| CEDAZURIDINE | — | Cytidine deaminase inhibitor | Approved |
| AZACITIDINE | — | DNA (cytosine-5)-methyltransferase 3A inhibitor | Approved |
| ZOSUQUIDAR | — | P-glycoprotein 1 inhibitor | Phase 3 |
| VENETOCLAX | — | Apoptosis regulator Bcl-2 inhibitor | Phase 3 |
| VALSPODAR | — | P-glycoprotein 1 inhibitor | Phase 3 |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
United States (FDA): Azacitidine approved via multiple pathways: NDA050794 (original), NDA208216, NDA214120; ANDA applications (201537, 204949, 207234, 207475, 207518, 209337, 209540, 210748, 211549, 212128, 212580, 215066, 215765, 215905, 217453, 218751) from 19 generic sponsors including Accord, Actavis, Amneal, Bristol-Myers, Cipla, Dr Reddy's, Teva, and others. APR-246 regulatory status not yet disclosed.
European Union (EMA): Azacitidine approved with 7 marketing authorizations (EMEA/H/C/000978, 004761, 004984, 005075, 005147, 005300, 006154) from MAHs including Accord Healthcare S.L.U., Bristol-Myers Squibb Pharma EEIG, Celgene Europe BV, Fresenius Kabi Deutschland GmbH, Mylan Pharmaceuticals Limited, and betapharm Arzneimittel GmbH. Authorization dates range from December 2025 to August 2026. APR-246 regulatory status not yet disclosed.
Australia (TGA): Azacitidine approved and PBS-listed since August 1, 2017 (PBS codes 12771E, 12784W, 13028Q, 13033Y, 13036D, 13038F, 13039G, 13040H, 13042K, 13044M) from Accord Healthcare Pty. Ltd., Bristol-Myers Squibb Australia Pty Ltd, Dr Reddy's Laboratories (Australia) Pty Ltd, EUGIA PHARMA (AUSTRALIA) PTY LTD, and Juno Pharmaceuticals Pty Ltd.
China (NMPA): Azacitidine in clinical trials; 5 active NCT studies registered (NCT05140811, NCT05144243, NCT05675813, NCT06386302, NCT06449482). Approved status not yet disclosed.
APR-246 + Combination Program: Regulatory pathway and filing status not yet disclosed. Phase 3 completion as of March 18, 2025 suggests potential regulatory submission in development.
APR-246 + azacitidine is an investigational combination therapy being developed for myelodysplastic syndrome (MDS), a group of clonal hematopoietic disorders characterized by dysplasia, cytopenia, and risk of progression to acute myeloid leukemia.
The program has completed Phase 3 development as of March 18, 2025. Specific results and regulatory filing status have not yet been disclosed.
Aprea Therapeutics is the sponsor and developer of the APR-246 + azacitidine combination program (internal code A18-15331).
The combination is administered orally. Azacitidine is confirmed as an oral formulation; APR-246 administration route details are not yet disclosed.
The specific mechanism of action for APR-246 has not yet been disclosed by Aprea Therapeutics.
Azacitidine is a hypomethylating agent classified as an antineoplastic and immunomodulating agent (ATC code L01) that functions through DNA methylation inhibition to restore normal gene expression in dysplastic cells.
Yes, azacitidine is FDA-approved with multiple ANDA and NDA approvals from 19+ manufacturers including Bristol-Myers Squibb, Accord Healthcare, Dr Reddy's Laboratories, and others.
Yes, azacitidine is approved by the European Medicines Agency (EMA) with 7 marketing authorizations from multiple manufacturers including Bristol-Myers Squibb, Accord Healthcare, Celgene Europe, and Fresenius Kabi, with authorization dates from December 2025 to August 2026.
Yes, azacitidine is approved in Australia and PBS-listed since August 1, 2017, with 10 PBS codes from manufacturers including Accord Healthcare, Bristol-Myers Squibb Australia, and Dr Reddy's Laboratories.
The pivotal Phase 3 trial is NCT03745716, which evaluates the combination therapy in MDS patients. Results have not yet been reported.
Competing approved therapies include VYXEOS Liposomal (Jazz Pharmaceuticals), IMBRUVICA (Janssen-Cilag), AFINITOR (Novartis), INLYTA (Pfizer), KYPROLIS (Amgen), and various hypomethylating agents. Azacitidine monotherapy is also widely available as a generic from multiple manufacturers.
The specific molecular target of APR-246 has not yet been disclosed.
The combination is a small-molecule oral therapy pairing an investigational agent (APR-246) with an established hypomethylating agent (azacitidine).
No partner or licensing arrangement has been disclosed for the APR-246 + azacitidine program; Aprea Therapeutics is the sole sponsor.
Projected peak sales figures have not been disclosed.
The first disclosure date has not been disclosed; the program is registered under internal code A18-15331 and is publicly tracked via NCT03745716.
The expected next milestone and its timing have not been disclosed. Potential catalysts include regulatory submission announcements and approval decisions.
APR-246 + azacitidine → Drug → Target → Indication → Company → Trials → Competitors
Strategic Implications: Aprea Therapeutics' Phase 3 completion of APR-246 + azacitidine represents a significant inflection point for the program. The combination strategy leverages the established efficacy and safety profile of azacitidine while introducing APR-246 as a potential synergistic agent. Completion of Phase 3 development positions the program for potential regulatory submission, though timing and jurisdiction priorities remain undisclosed.
Competitive Implications: The program enters a competitive MDS market dominated by hypomethylating agents and emerging targeted therapies. Success depends on demonstrating superiority or non-inferiority to azacitidine monotherapy with acceptable safety. The availability of generic azacitidine from 19+ manufacturers creates pricing pressure and establishes a low-cost baseline comparator. Differentiation requires compelling efficacy data and potential for improved outcomes in resistant or relapsed populations.
Future Catalysts: Key near-term catalysts include disclosure of Phase 3 results (efficacy, safety, tolerability endpoints), regulatory filing announcements, and potential breakthrough or accelerated designation pathways. Post-marketing surveillance data for azacitidine across multiple geographies provides real-world context for combination benefit assessment.
Expected Milestones: Regulatory submission timing, potential FDA or EMA interactions, and approval decisions represent critical milestones. Commercial launch strategy, manufacturing scale-up, and reimbursement negotiations will follow regulatory clearance. The program's success hinges on Phase 3 data quality, regulatory acceptance, and market differentiation versus established MDS therapies.
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Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.