BIIB074 · program
Vixotrigine for Neuropathic pain
Biogen's neuropathic-pain program of vixotrigine (BIIB074), a use-dependent broad-spectrum Nav channel blocker acquired with Convergence Pharmaceuticals in February 2015 ($200M upfront + up to $475M milestones; $424.6M of IPR&D recognized) — discontinued in December 2022. The program spanned four neuropathic-pain populations. Trigeminal neuralgia: a Phase 2a randomized-withdrawal study (NCT01540630, n=67 enrolled/29 randomized) supported further development, and two Phase 3 trials (802NP301/NCT03070132, 802NP302/NCT03637387) were registered in 2017–2018 — but 'numerous delays in the initiation of Phase 3 studies' (Biogen FY2022 10-K), including an FDA-requested additional clinical trial completed during 2022, meant neither ever enrolled a patient (both WITHDRAWN, actual enrollment 0, 'Sponsor Decision'); Biogen took a $44.3M TN impairment in Q1 2021 for the delay. Lumbosacral radiculopathy (sciatica): the Phase 2b study (NCT02935608, n=502) missed its primary and secondary efficacy endpoints, and its open-label extension (NCT02957617) was terminated 2019-02-07 with development in that indication discontinued. Small fiber neuropathy: the Phase 2 CONVEY study (NCT03339336, n=265 enrolled/123 randomized after early sponsor closure) reported topline 2021-09-16 — the 200 mg BID arm met the primary endpoint (change in average daily pain at week 12, p=0.050) while 350 mg BID missed (p=0.70). Biogen nonetheless discontinued all further development of vixotrigine in December 2022 for trigeminal neuralgia and diabetic painful neuropathy 'based on regulatory, development and commercialization challenges', recognizing a $119.6M impairment that reduced the asset's book value to zero and zeroing the Convergence contingent-consideration obligation (~$209.1M pre-tax gain). The two Phase 3 registrations were withdrawn on ClinicalTrials.gov in May 2023.
Development timeline
- Biogen FY2022 Form 10-K: 'In December 2022 we discontinued further development of vixotrigine (BIIB074) for the potential treatment of trigeminal neuralgia (TGN) and diabetic painful neuropathy (DPN), based on regulatory, development and commercialization challenges.' FY2022 impairment of $119.6M (DPN) reduced the IPR&D book value to zero; the Convergence contingent-consideration obligation was adjusted to zero (~$209.1M pre-tax gain; the year's total contingent-consideration reduction related to vixotrigine was ~$195.4M net). Exact day in December 2022 not disclosed — changed_at is a month-precision anchor at 2022-12-31. The two Phase 3 registrations were withdrawn on ClinicalTrials.gov 2023-05-06. No event code exists for a program discontinuation, so this row is the canonical record of it.↗
- mixedPhase 2 CONVEY topline in painful small fiber neuropathy: vixotrigine 200 mg BID met the primary endpoint (change from baseline in average daily pain at Week 12 of the double-blind period, p=0.050 vs placebo); 350 mg BID did not (p=0.70).↗
- Trial terminatedPhase 2 CONVEY study in small fiber neuropathy closed early by sponsor decision
- Phase 3 trigeminal-neuralgia trial 802NP301 (NCT03070132) first posted on ClinicalTrials.gov 2017-03-03; sister study 802NP302 (NCT03637387) posted 2018-08-20. REGISTERED, NEVER ENROLLED: both ended WITHDRAWN with actual enrollment 0 ('Sponsor Decision'). Per Biogen's FY2022 10-K there were 'numerous delays in the initiation of Phase 3 studies' for TGN and DPN; Biogen engaged the FDA on Phase 3 design and ran an FDA-relevant additional clinical trial (completed during 2022) whose performance further delayed initiation, driving a $44.3M TN impairment in Q1 2021. Biogen's pipeline listed vixotrigine at Phase 3 for TN during this period; the peak phase actually dosed was Phase 2.
- AcquisitionBiogen Idec to acquire Convergence Pharmaceuticals, gaining vixotrigine (then CNV1014802)↗
- First Phase 2 start under Convergence: the crossover study of CNV1014802 in neuropathic pain from lumbosacral radiculopathy (NCT01561027, n=82, started April 2011). The Phase 2a trigeminal-neuralgia randomized-withdrawal study (NCT01540630) followed in March 2012 and completed March 2014 (published Zakrzewska et al., Lancet Neurol 2017). Biogen acquired Convergence in February 2015 on the strength of this data (see acquisition event).
- First-in-human single-dose escalation of GSK1014802 started under GlaxoSmithKline (NCT00488566). The earliest GSK Phase 1s were registered under bipolar-disorder conditions (also NCT00908154, repeat-dose, 2008) — GSK briefly explored the mechanism in mood disorders before the ion-channel portfolio was spun out into Convergence Pharmaceuticals (2010), which repositioned the molecule (as CNV1014802) for neuropathic pain.
Readouts
- 2021-09-16ReportedTopline datamixedNCT03339336
Phase 2 CONVEY topline in painful small fiber neuropathy: vixotrigine 200 mg BID met the primary endpoint (change from baseline in average daily pain at Week 12 of the double-blind period, p=0.050 vs placebo); 350 mg BID did not (p=0.70). ↗
Clinical trials in Neuropathic pain
NCT03339336Phase 2Discontinuedn=265
CONVEY: Efficacy and Safety Study of BIIB074 in Participants With Small Fiber Neuropathy
NCT02957617Phase 2Discontinuedn=302
Extension Study to Evaluate the Long-Term Safety, Tolerability, and Maintenance of Effect of BIIB074 (Neuropathic Pain From Lumbosacral Radiculopathy)
NCT02935608Phase 2Completedn=502
Study to Evaluate the Efficacy and Safety of BIIB074 in Neuropathic Pain From Lumbosacral Radiculopathy
NCT02917187Phase 2Completedn=8
A Phase 2a Study of BIIB074 in the Treatment of Erythromelalgia
NCT01540630Phase 2Completedn=67
A Phase IIa Withdrawal Study of CNV1014802 in Patients With Trigeminal Neuralgia
NCT01561027Phase 2Completedn=82
Crossover Study of CNV1014802 in Subjects With Neuropathic Pain From Lumbosacral Radiculopathy
NCT03070132802NP301Phase 3Discontinued
802NP301 Efficacy and Safety Study of BIIB074 in Participants With Trigeminal Neuralgia
NCT03637387802NP302Phase 3Discontinued
802NP302 Efficacy and Safety Study of BIIB074 in Participants With Trigeminal Neuralgia
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Vixotrigine oral tablet (150–350 mg, BID/TID) Phase 2 CONVEY (small fiber neuropathy): 200 mg or 350 mg PO twice daily. Phase 2a trigeminal neuralgia: 150 mg three times daily. Phase 2b lumbosacral radiculopathy: up to 350 mg twice daily. A reformulation/food-effect study (NCT02951221) tested a new oral formulation in 2016–2017. | Oral | Twice daily | — |
Mechanism of action
Use- and state-dependent blocker of voltage-gated sodium (Nav) channels. Vixotrigine preferentially binds the inactivated channel state, so inhibition is enhanced at depolarized potentials and during high-frequency firing — conferring selectivity for the hyperexcitable, pain-associated signalling of ectopically firing sensory neurons over normal low-frequency transmission. Developed on a Nav1.7 (SCN9A) rationale (human gain-of-function Nav1.7 mutations cause pain disorders including some trigeminal neuralgia and inherited erythromelalgia), but Biogen's systematic characterization showed broad-spectrum activity: use-dependent IC50 values of 1.76–5.12 μM across peripheral and CNS Nav subtypes, with more profound state-dependent inhibition than carbamazepine and a spectrum distinct from Nav1.7- and Nav1.8-selective blockers. It rapidly inhibits Navs, prolongs recovery from fast inactivation, and shifts steady-state inactivation curves in rodent dorsal root ganglion neurons.
| Target | Action | Affinity |
|---|---|---|
| Nav1.7primarySCN9A | Inhibitor | —ⓘ |
← Full BIIB074 compound page (identity, identifiers, all indications)
Sources
- Biogen Announces Positive Topline Results from Phase 2 CONVEY Study in Small Fiber Neuropathy (2021-09-16) — Biogen (via GlobeNewswire)
- Biogen Idec to Expand Neuropathic Pain Portfolio with the Acquisition of Convergence Pharmaceuticals (2015-01-12) — Biogen
- Biogen Inc. Form 10-K for fiscal year 2022 (filed 2023-02-15) — December 2022 discontinuation of vixotrigine (BIIB074) for TGN and DPN; $119.6M impairment; Convergence contingent consideration zeroed; Phase 3 delay history and Q1 2021 $44.3M TN impairment — U.S. Securities and Exchange Commission (EDGAR)
- Hinckley CA, Kuryshev Y, et al. Characterization of Vixotrigine, a Broad-Spectrum Voltage-Gated Sodium Channel Blocker. Mol Pharmacol 2021;99(1):49-59 — Molecular Pharmacology (ASPET) / PubMed
- Kenney et al. Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): a phase 2 placebo-controlled enriched-enrolment randomised withdrawal study. eClinicalMedicine 2023 — eClinicalMedicine (The Lancet Discovery Science) via PubMed Central
- NCT00488566 — GSK first-in-human single-dose escalation of GSK1014802 (2007; registered under bipolar-disorder conditions) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT01540630 — A Phase IIa Withdrawal Study of CNV1014802 in Patients With Trigeminal Neuralgia — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT01561027 — Crossover Study of CNV1014802 in Subjects With Neuropathic Pain From Lumbosacral Radiculopathy — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT02917187 — A Phase 2a Study of BIIB074 in the Treatment of Erythromelalgia — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT02935608 — Phase 2b Study to Evaluate the Efficacy and Safety of BIIB074 in Neuropathic Pain From Lumbosacral Radiculopathy — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT02957617 — Open-label extension in lumbosacral radiculopathy (terminated: parent study missed primary and secondary efficacy endpoints; development in the indication discontinued) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT03070132 — 802NP301 Phase 3 in Trigeminal Neuralgia (WITHDRAWN, enrollment 0, Sponsor Decision) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT03339336 — CONVEY: Efficacy and Safety Study of BIIB074 in Participants With Small Fiber Neuropathy (terminated: sponsor decision, not safety) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT03637387 — 802NP302 Phase 3 in Trigeminal Neuralgia (WITHDRAWN, enrollment 0, Sponsor Decision) — ClinicalTrials.gov (U.S. National Library of Medicine)