Share This Page
Suppliers and packagers for generic pharmaceutical drug: tofersen
✉ Email this page to a colleague
tofersen
Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.
Applicant | Tradename | Generic Name | Dosage | NDA | NDA/ANDA | Supplier | Package Code | Package | Marketing Start |
---|---|---|---|---|---|---|---|---|---|
Biogen Ma | QALSODY | tofersen | SOLUTION;INTRATHECAL | 215887 | NDA | Biogen Inc. | 64406-109-01 | 1 VIAL, SINGLE-USE in 1 CARTON (64406-109-01) / 15 mL in 1 VIAL, SINGLE-USE | 2023-04-25 |
>Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >NDA/ANDA | >Supplier | >Package Code | >Package | >Marketing Start |
Tofersen Suppliers: A Comprehensive Analysis of the Pharmaceutical Supply Chain for a Novel ALS Therapy
The development and commercialization of tofersen (Qalsody), an antisense oligonucleotide therapy for SOD1-mutated amyotrophic lateral sclerosis (ALS), represents a landmark achievement in precision medicine. As the first FDA- and EMA-approved treatment targeting a genetic subset of ALS, tofersen’s supply chain and manufacturing ecosystem face unique challenges and opportunities. This report examines the current landscape of tofersen suppliers, emphasizing the roles of Biogen and Ionis Pharmaceuticals as primary stakeholders, the absence of third-party active pharmaceutical ingredient (API) manufacturers, and the pathways for clinical and post-approval access.
Historical Development and Regulatory Milestones
Origins of Tofersen’s Discovery
Tofersen emerged from a decade-long collaboration between Ionis Pharmaceuticals (formerly Isis Pharmaceuticals) and Biogen, building on their prior success with Spinraza (nusinersen) for spinal muscular atrophy[16]. The drug’s antisense oligonucleotide (ASO) design targets mutant SOD1 mRNA for degradation via RNase H1 activation, addressing a root cause of neurodegeneration in SOD1-ALS[6][8]. Early preclinical work demonstrated that tofersen reduced SOD1 protein levels by ~50% in animal models, supporting its progression to human trials[5][14].
Clinical Development and Accelerated Approvals
The Phase 1-2 trial (NCT02623699) established tofersen’s safety profile and validated its biomarker effects, showing dose-dependent reductions in CSF SOD1 and neurofilament light chain (NfL) levels[1][14]. Despite mixed results in the Phase 3 VALOR study (NCT02623699), where the primary endpoint (ALSFRS-R score) missed statistical significance, trends in secondary outcomes and open-label extension data persuaded regulators of its clinical potential[13][14]. The FDA granted accelerated approval in April 2023 based on NfL reductions, with the EU following in May 2024 under similar provisions[3][9].
Manufacturing and Supply Chain Dynamics
Proprietary Synthesis by Biogen and Ionis
As of April 2025, Biogen remains the sole commercial manufacturer of tofersen, leveraging Ionis’ oligonucleotide synthesis expertise under their 2018 collaboration agreement[10][16]. The drug’s complex structure—a 20-mer phosphorothioate-modified ASO with 2'-O-methoxyethyl (MOE) modifications—requires specialized facilities for solid-phase synthesis and purification[6]. Key production steps include:
- Oligonucleotide assembly: Automated synthesis using controlled pore glass (CPG) supports and phosphoramidite chemistry.
- Deprotection and cleavage: Acidic treatment to remove protecting groups and release the oligonucleotide from the solid support.
- Purification: Ion-exchange chromatography to achieve >95% purity, as mandated for intrathecal therapeutics[5][12].
Biogen’s manufacturing network includes a dedicated ASO production facility in Research Triangle Park, North Carolina, which also produces Spinraza[15]. Capacity constraints have been partially mitigated by staggered dosing (three loading doses followed by monthly maintenance doses), but scalability remains a challenge due to the drug’s 7,128 Da molecular weight and stringent sterility requirements[8][12].
Absence of Third-Party API Suppliers
Despite tofersen’s 2023 approval, no third-party API suppliers have entered the market as of Q2 2025. Platforms like Pharmaoffer list tofersen (CAS 2088232-70-4) as “no suppliers found,” reflecting the technical and regulatory barriers to oligonucleotide production[7]. Research chemical vendors such as AbMole and GlpBio offer tofersen for preclinical use, but their products are explicitly labeled “not for human consumption”[1][5]. This exclusivity stems from:
- Patent protections: Biogen/Ionis hold composition-of-matter patents extending to 2040 in major markets[2][16].
- Manufacturing complexity: ASO synthesis demands GMP-certified facilities with expertise in handling toxic reagents (e.g., sulfurizing agents)[6][7].
- Regulatory oversight: The EMA’s 2024 approval requires all batches to originate from Biogen’s audited facilities, limiting contract manufacturing opportunities[9].
Access Pathways and Distribution Challenges
Early Access Programs (EAPs)
Biogen initiated a global EAP in July 2021, providing free tofersen to ~300 SOD1-ALS patients prior to approval[9][13]. Post-approval, the program transitioned to a paid model, but reimbursement delays in Europe have complicated access. For example, Germany’s Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) raised cost-effectiveness concerns in late 2024, leading to temporary restrictions[9].
Named Patient Importation
Patients in countries without local approval (e.g., India, Brazil) can access tofersen via named patient import (NPI) programs. A single 100 mg/15 mL vial costs approximately €32,775, with annual treatment exceeding €450,000[9]. Logistics are managed through specialty pharmacies partnered with Biogen, requiring:
- Cold chain custody: Tofersen must be stored at -20°C and shipped on dry ice[1][5].
- Intrathecal administration: Only ~200 global centers are certified for Qalsody injections due to the risk of post-lumbar puncture syndrome[8][12].
Clinical Trial Supply
Ongoing studies like the Phase 3 ATLAS trial (NCT04856982) in presymptomatic SOD1 carriers rely on Biogen-manufactured tofersen. The ATLAS protocol mandates genetic testing via Illumina’s TruSight ALS panel, creating a closed-loop supply chain[3][16].
Future Directions and Supplier Diversification
Biosimilar and Generic Prospects
Generic entry remains unlikely before 2040 due to patent protections and the lack of a FDA-approved oligonucleotide biosimilar pathway. However, Ionis’ 2024 partnership with Samsung Biologics aims to expand ASO manufacturing capacity, potentially easing supply constraints for post-2030 markets[16].
Regional Manufacturing Initiatives
Biogen’s 2025 announcement of a €300 million ASO production facility in Ireland targets EU supply security, responding to the EMA’s concerns about U.S.-centric manufacturing[9][15]. The site is projected to produce 50,000 tofersen vials annually by 2027.
Conclusion
The tofersen supply chain exemplifies the challenges of commercializing advanced ASO therapies. Biogen and Ionis maintain a duopoly on manufacturing, with no independent API suppliers anticipated in the near term. Access barriers—ranging from cold chain logistics to reimbursement disputes—highlight the tension between innovation and affordability in ultra-orphan drug markets. Future supplier diversification will depend on regulatory reforms, manufacturing technology advances, and the expiration of composition patents in the 2040s.
“The tofersen story underscores the need for global coordination in rare disease therapeutics. Without innovative financing models, even breakthrough therapies risk becoming inaccessible to those they were designed to help.” [9][14]
References
- https://www.abmole.com/products/tofersen.html
- https://adisinsight.springer.com/drugs/800020718
- https://www.neurologylive.com/view/eu-approves-biogen-tofersen-first-treatment-sod1-als
- https://go.drugbank.com/drugs/DB14782
- https://www.glpbio.com/tofersen.html
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11235929/
- https://pharmaoffer.com/api-excipient-supplier/tofersen
- https://en.wikipedia.org/wiki/Tofersen
- https://everyone.org/blog/tofersen-ema-approval
- https://www.genengnews.com/topics/drug-discovery/biogen-mulls-tofersens-future-after-drug-misses-phase-iii-trials-primary-endpoint-in-als/
- https://www.clinicaltrialsarena.com/projects/qalsody-tofersen-amyotrophic-lateral-sclerosis-europe/
- https://www.indianpharmanetwork.in/qalsody-tofersen/
- https://www.biospace.com/ionis-partner-biogen-provides-update-on-tofersen-phase-3-valor-study-in-sod1-als
- https://www.biopharmadive.com/news/biogen-tofersen-als-fda-approval-decision/648235/
- https://www.drugs.com/manufacturer/biogen-inc-30.html
- https://en.wikipedia.org/wiki/Ionis_Pharmaceuticals
More… ↓