Teriflunomide
| Evidence Level: L1 | Predicted Indications: 1 |
Table of Contents
- Teriflunomide
- Teriflunomide: From No Local Marketing Authorization to Relapsing-Remitting Multiple Sclerosis
Teriflunomide: From No Local Marketing Authorization to Relapsing-Remitting Multiple Sclerosis
One-Sentence Summary
Teriflunomide (DrugBank DB08880) is not currently marketed in India, and no original indication data is available in this Evidence Pack. The TxGNN model predicts it may be effective for Relapsing-Remitting Multiple Sclerosis (RRMS), with 28 clinical trials and 19 publications currently supporting this direction — including two completed Phase 3 pivotal trials (TEMSO).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — drug not currently marketed in India, no license data on file |
| Predicted New Indication | Relapsing-Remitting Multiple Sclerosis (RRMS) |
| TxGNN Prediction Score | 99.24% |
| Evidence Level | L1 |
| India Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed original mechanism-of-action data is flagged as a data gap in this Evidence Pack (DG002). However, based on publicly available pharmacology, teriflunomide is a dihydroorotate dehydrogenase (DHODH) inhibitor that blocks de novo pyrimidine synthesis, selectively suppressing the proliferation of activated T- and B-lymphocytes. This immunomodulatory mechanism directly targets the autoimmune inflammatory process underlying relapsing-remitting multiple sclerosis.
Because no original indication is on record for this market (the drug has no local license), there is no “original vs. new indication” comparison to make in the conventional repurposing sense. Instead, the TxGNN prediction (score 0.992) aligns with teriflunomide’s already-established global clinical role: it is marketed internationally (e.g., as Aubagio) specifically for RRMS, and this role is directly substantiated by the pivotal TEMSO Phase 3 program included in the evidence below. In effect, this candidate represents a market-entry opportunity for an internationally validated RRMS therapy rather than a novel mechanistic repurposing hypothesis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00134563 | Phase 3 | Completed | 1,088 | TEMSO pivotal trial — randomized, double-blind, placebo-controlled; confirmed teriflunomide reduces relapse frequency and delays disability accumulation in RRMS |
| NCT00803049 | Phase 3 | Completed | 742 | TEMSO long-term extension — documented long-term safety and efficacy (relapse rate, disability progression, MRI) of teriflunomide 7 mg and 14 mg |
| NCT00883337 | Phase 3 | Completed | 324 | TENERE study — head-to-head comparison of teriflunomide vs. interferon beta-1a on time to treatment failure, relapse frequency, and fatigue |
| NCT03302442 | N/A | Completed | 3,000 | French MS Observatory cohort comparing dimethyl fumarate vs. teriflunomide on clinical and MRI outcomes |
| NCT02776072 | N/A | Completed | 2,978 | Multicenter global retrospective real-world study of RRMS patients treated with DMF, glatiramer acetate, teriflunomide, or fingolimod |
| NCT02490982 | N/A | Completed | 106 | Investigator-initiated observational effectiveness study of teriflunomide in routine RRMS practice over ≥2 years |
| NCT03500328 | N/A | Active, not recruiting | 900 | Pragmatic trial (TREAT-MS) comparing early aggressive vs. escalation therapy strategies; teriflunomide included as a treatment arm |
| NCT00228163 | Phase 2 | Completed | 147 | Long-term extension of a Phase 2 teriflunomide safety and efficacy study in MS with relapses |
| NCT03535298 | Phase 4 | Active, not recruiting | 800 | DELIVER-MS — early intensive vs. escalation treatment approaches, with teriflunomide among first-line options |
| NCT04129736 | Phase 4 | Completed | 12 | Serum and cerebrospinal fluid concentration study of teriflunomide 14 mg daily in RRMS patients |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32757523 | 2020 | RCT | NEJM | ASCLEPIOS trial — ofatumumab vs. teriflunomide in relapsing MS; teriflunomide used as active comparator |
| 36001711 | 2022 | RCT | NEJM | Ublituximab vs. teriflunomide in relapsing MS |
| 40202623 | 2025 | RCT | NEJM | Tolebrutinib vs. teriflunomide in relapsing MS |
| 26758290 | 2016 | RCT | CNS Drugs | Review of EU SmPC for teriflunomide with key clinical and safety outcomes for RRMS |
| 39307151 | 2024 | RCT | Lancet Neurology | evolutionRMS1/2 — evobrutinib vs. teriflunomide, Phase 3 active-comparator trials |
| 35266417 | 2022 | RCT | Mult Scler | ASCLEPIOS I/II — ofatumumab superior to teriflunomide in treatment-naïve RRMS patients |
| 38174776 | 2024 | Network Meta-analysis | Cochrane Database Syst Rev | Comparative effectiveness of immunomodulators/immunosuppressants (including teriflunomide) in RRMS |
| 37691530 | 2023 | Extension/Observational | Mult Scler | ALITHIOS open-label extension — 4-year ofatumumab data vs. teriflunomide comparator |
| 31098896 | 2019 | Review | Drugs | Comprehensive review of teriflunomide’s efficacy and tolerability in RRMS based on RCT and real-world evidence |
| 33620411 | 2021 | Review | JAMA | General review of MS diagnosis and treatment landscape |
India Market Information
Teriflunomide currently has no marketing authorization in India (0 registrations on file). No local product, brand name, or approved indication text is available in this Evidence Pack.
Safety Considerations
Drug Interactions: A total of 561 drug-drug interactions are on record. Selected Major-level interactions include: Acarbose, Hydrocortisone, Pioglitazone, Bupropion, Triamcinolone, Acetylsalicylic acid, Dexamethasone, Betamethasone, Budesonide, Chenodeoxycholic acid, Clarithromycin, Minocycline, Oxandrolone, and Oxymetholone. Moderate-level interactions include Alosetron, Cimetidine, Empagliflozin, and Sitagliptin.
Local key warnings and contraindication data are not currently available; please refer to the international product label (e.g., Aubagio SmPC/USPI) for full prescribing information pending local filing.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The efficacy evidence is strong (L1) — two completed Phase 3 pivotal trials (TEMSO, TEMSO extension) plus a head-to-head Phase 3 comparator trial (TENERE) directly establish teriflunomide’s efficacy and safety in RRMS, and this is reinforced by an extensive body of comparator RCTs (ofatumumab, ublituximab, tolebrutinib, evobrutinib) using teriflunomide as the active control. However, this drug has no current marketing authorization in India, and local label/warning/contraindication data (DG001) is a Blocking gap that prevents a complete safety initial assessment (S1).
To proceed, the following is needed:
- Local regulatory filing status and TFDA/CDSCO-approved label, warnings, and contraindications (resolves DG001, currently Blocking)
- Confirmed DrugBank-sourced mechanism-of-action documentation (resolves DG002)
- A local safety monitoring plan, particularly given the extensive DDI profile (561 interactions) and known teratogenicity/hepatotoxicity concerns associated with DHODH inhibitors
- Assessment of the local regulatory pathway for market entry, given the drug is not yet registered
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.