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Huntington’s Disease Clinical Trials Corner: April 2020

Abstract

In this edition of the Huntington’s Disease Clinical Trials Corner we expand on the UniQure AMT-130 and on the Neurocrine Biosciences KINECT-HD trials, and list all currently registered and ongoing clinical trials in Huntington’s disease.

INTRODUCTION

The Huntington’s Disease Clinical Trials Corner is a regular section devoted to highlighting ongoing and recently completed clinical trials in Huntington’s disease (HD). Clinical trials previously reviewed by the Huntington’s Disease Clinical Trials Corner are listed in Table 1.

Table 1

Clinical trials previously reviewed by the Huntington’s Disease Clinical Trials Corner. *IONIS-HTTRx, RG6042 and tominersen refer to the same molecule

Trial nameInterventionEdition
NCT02519036IONIS-HTTRxIONIS-HTTRx*September 2017 [3]
NCT02215616LEGATO-HDLaquinimod
NCT02197130AmaryllisPF-02545920
NCT02006472PRIDE-HDPridopidine
NCT03225833PRECISION-HD1WVE-120101February 2018 [13]
NCT03225846PRECISION-HD2WVE-120102
NCT01795859FIRST-HDDeutetrabenazine
NCT02481674SIGNALVX15/2503August 2018 [14]
NCT00712426CREST-ECreatine
NCT03761849GENERATION-HD1RG6042*January 2019 [15]
NCT03344601PACE-HDPhysical activity
NCT02535884HD-DBSDeep brain stimulationJune 2019 [16]
NCT02453061TRIHEP3Triheptanoin
NCT04120493AMT-130AAV5-miHTTApril 2020
NCT04102579KINECT-HDValbenazine

In this edition, we highlight the UniQure AMT-130 (NCT04120493) [1], and the Neurocrine Biosciences KINECT-HD trial (NCT04102579) [2]. We tabulate all currently registered and ongoing clinical trials in Tables 2 to 4. For further details on the methodology used, please refer to the first edition of Huntington’s Disease Clinical Trials Corner [3].

Table 2

Ongoing pharmacological clinical trials registered at the World Health Organization (WHO) International Clinical Trials Research Platform (ICTRP) for people with Huntington’s disease (HD). N/S, not specified; PD, Parkinson’s disease; VMAT2, Vesicular Monoamine Transporter 2. Note: IONIS-HTTRx, ISIS 443139, RG6042 and tominersen refer to the same molecule. New trials since the last Clinical Trials Corner are indicated by *

Registration IDTrial nameInterventionMechanism of ActionPopulationComparisonMain outcomeStudy designEstimated EnrolmentSponsorLocation
NCT04201834*RisperidoneDopamine antagonistEarly and moderate HD with choreaNoneChange in motor scales at 12 weeksNon-randomized, open label (assessor-blind), uncontrolled trial12University of RochesterUSA (single centre)
NCT04071639*Haloperidol, risperidone, sertraline and coenzyme Q10Multiple (dopamine antagonists, selective serotonin reuptake inhibitor, dietary supplement)Early and moderate HDCoenzyme Q10Efficacy at 5 yearsRandomized, open label, controlled, parallel trial100Second Affiliated Hospital, School of Medicine, Zhejiang UniversityChina (single centre)
NCT04120493*AMT-130rAAV5-miHTTNonselective miRNAEarly HDSham interventionSafety at 18 monthsRandomized, double-blind, sham-controlled, parallel trial26UniQure Biopharma B.V.USA (multi-centre)
NCT04102579*KINECT-HDValbenazineVMAT2 inhibitorHD with choreaPlaceboEfficacy at 12 weeksRandomized, double-blind, placebo-controlled, parallel trial120Neurocrine Biosciences, Huntington Study GroupUSA (multi-centre)
EUCTR2019-002178-30-DK*WVE-120102Allele-selective antisense oligonucleotideHDNoneSafety and tolerability at 97 weeksOpen-label extension70Wave Life Sciences Ltd.Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT04000594*GEN-PEAKRG6042Allele- nonselective antisense oligonucleotideHDNonePharmacodynamics and pharmacokinetics at multiple timepoints until 6 monthsNon-randomized. open-label, multiple-dose, parallel trial20Hoffmann-La RocheThe Netherlands and UK (multi-centre)
NCT03980938*Neflamapimodp38α MAPK inhibitorEarly HDPlaceboChange in cognitive scales at 10 weeksRandomized, double-blind, placebo-controlled, cross-over trial16EIP Pharma Inc, Voisin Consulting, Inc.UK (single centre)
NCT03842969GEN-EXTENDRG6042Allele- nonselective antisense oligonucleotideHDNoneSafety and tolerability at up to 5 yearsOpen-label extension1050Hoffmann-La RocheUSA, Canada, Europe (multi-centre)
NCT03761849GENERATION-HD1RG6042Allele- nonselective antisense oligonucleotideHDPlaceboClinical efficacy at 101 weeksRandomized, double-blind, placebo-controlled, parallel trial909Hoffmann-La RocheUSA, Canada, Europe (multi-centre)
NCT03515213FenofibratePPARα agonistHDPlaceboPharmacodynamics at 6 monthsRandomized, double-blind, placebo-controlled, parallel trial20University of California, IrvineUSA (single centre)
NCT03764215Tasigna HDNilotinibSelective Bcr-Abl tyrosine kinase inihbitorHDNoneSafety, tolerability and pharmacodynamics at 3 monthsOpen label, multiple ascending dose20Georgetown UniversityUSA (single centre)
NCT03225833PRECISION-HD1WVE-120101Allele-selective antisense oligonucleotideHDPlaceboSafety and tolerability at 1 and 120 daysRandomized, double-blind, placebo-controlled, combined single ascending dose/multiple ascending dose trial48Wave Life Sciences Ltd.Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT03225846PRECISION-HD2WVE-120102Allele-selective antisense oligonucleotideHDPlaceboSafety and tolerability at 1 and 120 daysRandomized, double-blind, placebo-controlled, combined single ascending dose/multiple ascending dose trial60Wave Life Sciences Ltd.Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT02453061TRIHEP 3TriheptanoinAnaplerotic therapyHDSafflower oilPharmacodynamic efficacy at 6 monthsRandomized, double-blind, controlled, parallel trial100Institut National de la Santé Et de la Recherche Médicale, Ultragenyx Pharmaceutical IncFrance, Netherlands (multi-centre)
NCT02509793TetrabenazineVMAT2 inhibitorHD with impulsivityNoneCognitive and behavioural effects at 8 weeksSingle group, open-label trial20University of Texas Health Science Center, and H. Lundbeck A/SUSA (single centre)
NCT02481674SIGNALVX15/2503Anti-semaphorin 4D monoclonal antibodyLate premanifest or early HDPlaceboSafety and tolerability at 15 and 21 monthsRandomized, double-blind, placebo-controlled, parallel trial240Vaccinex Inc., Huntington Study GroupUSA (multi-centre)
EUCTR2013-002545-10-SEOSU6162Open1309(-)-OSU616Monoaminergic stabilizerHD, PD, brain trauma, stroke, myalgic encephalomyelitis and narcolepsyNoneSafety at 3, 6 and 12 monthsSingle group, open-label trial240A. Carlsson Research ABSweden (multi-centre)
NCT00514774UDCA-HDUrsodiolBile acidHDPlaceboSafety, tolerability and pharmacokinetics at 35 daysRandomized, double-blind, placebo-controlled, parallel trial21Oregon Health and Science University, Huntington Study Group, Huntington Society of CanadaN/S
Table 3

Ongoing invasive non-pharmacological clinical trials registered at the World Health Organization (WHO) International Clinical Trials Research Platform (ICTRP) for people with Huntington’s disease (HD). AD, Alzheimer’s disease, CBD; Corticobasal Degeneration; DBS, deep brain stimulation; ET, Essential Tremor; GP, Globus pallidus; HT, Holmes Tremor; MNC, mononuclear cells; MS, Multiple Sclerosis; PD, Parkinson’s disease; TD, Tardive dyskinesia; WD, Wilson’s disease. New trials since the last Clinical Trials Corner are indicated by *

Registration IDTrial nameInterventionMechanism of ActionPopulationComparisonMain outcomeStudy designEsimated EnrolmentSponsorLocation
NCT04244513*GPi DBSDeep brain stimulationHD with choreaSham interventionEfficacy at 3 and 6 monthsRandomized, double-blind, sham-controlled, cross-over trial40Beijing Municipal Administration of Hospitals, MedtronicChina (multi-centre)
NCT04219241*ADORE-EXTCellavitaStem cell therapyHDNoneEfficacy and safety at 2 yearsOpen label extension35Azidus Brasil, Cellavita Pesquisa Científica LtdaBrazil (single centre)
ISRCTN52651778TRIDENTFoetal stem cell transplantStem cell therapyEarly stage HDUsual careSafety at 4 weeksRandomized, open label, controlled, parallel trial30Cardiff UniversityUK (single centre)
NCT02728115SAVE-DHCellavitaStem cell therapyHDNoneSafety at 5 yearsNon-randomized, open label, uncontrolled, parallel trial6Azidus BrasilBrazil (single centre)
NCT03252535ADORE-HDCellavitaStem cell therapyHDPlaceboEfficacy at 120 daysRandomized, double-blind, placebo-controlled, parallel trial35Azidus BrasilBrazil (single centre)
NCT03297177Autologous stem/stromal cellsAutologous stem/stromal cell injectionHD, AD, PD, CBD, MSNoneSafety at 5 yearsSingle group, open-label trial300Healeon Medical Inc, Global Alliance for Regenerative Medicine, Regeneris MedicalUSA and Honduras (multi-centre)
NCT02535884HD-DBSGP DBSDeep brain stimulationModerate HD with choreaSham interventionEfficacy at 12 monthsRandomized, double-blind, sham-controlled, parallel trial50Heinrich-Heine University, KKS Netzwerk, Medtronic, The George Institute, EHDN, CHDI Foundation, Inc.Austria, France Germany, Switzerland (multi-centre)
NCT01834053BMACHCBone Marrow Derived MNC transplantBone marrow transplantHD with choreaNoneCognitive and behavioural effects at 6 monthsSingle group, open-label trial50Chaitanya Hospital, PuneIndia (single centre)
NCT02252380Magnetic Resonance Guided Focused UltrasoundExtracranial stereotactic radioablationHD, ET, HT, PD, WD, dystonia, TD, or orofacial dyskinesiasNoneAdverse events after the procedureSingle group, open-label trial10InSightecCanada (single centre)
Table 4

Ongoing non-invasive non-pharmacological clinical trials registered at the World Health Organization (WHO) International Clinical Trials Research Platform (ICTRP) for people with Huntington’s disease (HD). AD, Alzheimer’s disease; ALS, Amyotrophic Lateral Sclerosis; ET, Essential Tremor; HT, Holmes Tremor; MS, Multiple Sclerosis; PD, Parkinson’s disease; TD, Tardive dyskinesia. New trials since the last Clinical Trials Corner are indicated by *

Registration IDTrial nameInterventionMechanism of ActionPopulationComparisonMain outcomeStudy designEsimated EnrolmentSponsorLocation
ACTRN12620000281998*Ketogenic dietHDNoneChange in cognition and motor scores at 12 weeksNon-randomized, open label, single group trial10Waikato HospitalNew Zealand (-)
ACTRN12619000870156*Transcranial alternating current stimulationTranscranial magnetic stimulationPremanifest and early HDSham interventionBiomarkersRandomized, open-label, cross-over trials60Monash University, Epworth Centre for Innovation in Mental HealthAustralia (single centre)
ACTRN12618001717246Multidisciplinary therapy programExercise, cognitive training, lifestyle guidance and social activitiesPremanifest HDStandard of careFeasibility and safetyClustered, non-randomized, open label, parallel trial40Edith Cowan University, Deakin University and LotterywestAustralia (two centres)
NCT03417583Neuropsychiatric treatment protocolMultidisciplinary interventionHD with neuropsychiatric symptomsStandard of careChange in quality of life at 18 monthsNon-randomized, assessor-blinded, parallel trial100Vanderbilt University Medical Center and Teva Pharmaceuticals USAUSA (single centre)
CTRI/2018/01/011359Repetitive transcranial magnetic stimulationTranscranial magnetic stimulationEarly to moderate HD and PDSham stimulationEfficacy at 5 daysRandomized, single-blind, placebo-controlled, parallel trial40Vinay GoyalIndia (single centre)
NCT03344601PACE-HDSupported structured aerobic exercise training programPhysiotherapyHDActivity as usualData completeness, recruitment, retention, safety, adherence, fidelity and acceptability at 12 monthsNested open-label, randomized controlled parallel trial120Cardiff University and CHDI Foundation, IncGermany, Spain and USA (multi-centre)
ACTRN12617001269325Swallowing skill trainingSpeech and language therapyHD and ALSNoneSwallowing function and quality of life at 2 weeksSingle group, open-label trial54University of CanterburyNew Zealand (single centre)

If you would like to draw attention to specific trials, please feel free to email us at: [email protected] and [email protected]

ONGOING CLINICAL TRIALS

A list of all ongoing clinical trials is given in Tables 2, 3 and 4.

In addition to the trials covered below, it is worth mentioning that Wave Life Sciences made a preliminary announcement of results from their ongoing PRECISION-HD2 trial (NCT03225846) [4]. This is a phase 1b/2a trial investigating WVE-120102, an intrathecal allele-selective antisense oligonucleotide (ASO). When compared with placebo, this drug was shown to reduce CSF mutant huntingtin by 12.4% (95% CI 0.40 to 24.58), while CSF total huntingtin and neurofilament light (NfL) remained unchanged. Whist statistically significant, this reduction was derived from a comparison of all ASO doses pooled together (mean change from baseline –6.0% [95% CI –9.57 to 4.85]) against a placebo arm showing a somewhat larger change than might be expected due to disease progression from natural history studies (mean change from baseline 9.5% [95% CI 1.77 to 20.38]). The ASO was also considered to be “generally safe and well tolerated among patients receiving doses up to 16 mg”. No results were disclosed about the PRECISION-HD1 trial (NCT03225833) [5], testing WVE-120101, another intrathecal allele-selective ASO targeting a different single-nucleotide polymorphism. As a result, a new 32 mg dosage cohort will added to both trials and further updates are awaited from the broader program [6].

AMT-130 (NCT04120493)

Study title: A Phase I/II, Randomized, Double-blind, Sham Control Study to Explore Safety, Tolerability, and Efficacy Signals of Multiple Ascending Doses of Striatally-Administered rAAV5-miHTT Total Huntingtin Gene (HTT) Lowering Therapy (AMT-130) in Early Manifest Huntington Disease [1].

Intervention: Single-time intrastriatal injection of AAV5-miHTT [7].

Description: The AMT-130 trial, sponsored by UniQure, aims to evaluate the safety, tolerability and proof-of-concept of a single-time bilateral intrastriatal injection of AAV5-miHTT in adults (25 to 65 years of age) with manifest HD (i.e. clinically symptomatic and genetically confirmed [CAG≥44]) and early disease stage, comparing with sham injection, for disease progression.

Individuals who have received any experimental agent or participation in the following are not eligible for this study: any investigational trial within 60 days or five half-lives prior to screening; with a deep brain stimulator in situ; with history of gene therapy, RNA or DNA targeted HD specific investigational agent, cell transplantation or other experimental cerebral surgery; contraindications for lumbar punctures or 3 Tesla MRI; putaminal and caudate volumes per side inferior to 2.5 and 2.0 cm3, respectively; brain or spinal cord pathology that may interfere with CSF homeostasis and circulation, increased intracranial pressure, malformations or tumours; hospitalization for major medical reason or major surgical procedure involving general anaesthesia within 12 weeks of screening; current use of medications to treat or that can aggravate chorea, or unstable concomitant medication within 3 months of screening.

This trial is an US-based, multi-centre, randomized, sham-controlled, double-blind, parallel study. It will have 3 study arms: the low dose group, where participants will receive a single total dose of 6×1012 genome copies of AAV5-miHTT via a MRI-guided convection-enhanced delivery; the high dose group, where participants will receive a single total dose of 6×1013 genome copies of AAV5-miHTT via a MRI-guided convection-enhanced delivery; and the imitation surgery arm, where participants will receive bilateral partial thickness burr holes with no intrastriatal injections. The study will last 5 years, where participants will be blind to treatment allocation for 18 months, followed by an unblinded period of 3.5 years.

The trial has already started recruitment [8], and has a recruitment target of 26 participants, across 4 sites. It will follow a multiple ascending dose design, with a first cohort of 10 participants (stage 2 HD; 6 randomized to low dose and 4 to sham surgery) and a second cohort of 16 participants (stage 1-2 HD; 10 randomized to high dose and 6 to sham surgery).

The primary outcome will be safety, measured at 18 months, and the secondary outcome will be CSF biomarkers, namely levels of the vector DNA and miRNA expression at 60 months. Other outcomes include: biofluid and imaging biomarkers; clinical scales such as the UHDRS motor, cognitive, behaviour and functional subscales, the Huntington’s Disease Cognitive Assessment Battery (HD-CAB), the Neuro-QoL, HDQLIFE and Hospital Anxiety and Depression Scale (HADS); and quantitate motor assessments (i.e. Q-Motor).

Sponsors/funders: UniQure Biopharma B.V..

Comments: The AAV5-miHTT is an engineered microRNA (miRNA) targeting both human wild-type and mutant huntingtin for degradation. It is delivered via an adeno-associated viral vector serotype 5 (AAV5). This is the first human trial of an AAV-mediated gene therapy in Huntington’s disease.

If it functions as intended, upon injection into the brain parenchyma using MRI-guided convection-enhanced delivery, the AAV5-miHTT will bind to cell receptors and will be internalised by neurons and transported to the nucleus. There, the miRNA will be uncoated from the viral vector and remains episomal. After expression and processing of the miHTT transgene by the endogenous RNA interference machinery into a hairpin structure, the miRNA is transported into the cytoplasm. There the mature miRNA will load in the RNA-induced silencing complex and bind huntingtin mRNA, targeting it for cleavage and degradation. In theory, this mechanism of action makes this method irreversible, and animal models have demonstrated long-lasting miRNA expression over time after a single injection.

The efficacy and safety of this miRNA and vector has been assessed in cultured human neurons, and in vivo in multiple animal models such as mice, non-human primates and transgenic minipigs. Transgene expression accompanied by huntingtin lowering has been seen in the injected and distant structures such as the cortex.

The selected vector – AAV5 – has been tested in 4 clinical studies across haematological and metabolic disorders. When given intravenously it appears safe and tolerable, showing low activity to pre-existing neutralizing antibodies. However this is the first time it has been used for intraparenchymal delivery into the brain.

The AAV5-miHTT will be injected to the caudate and putamen bilaterally via MRI-guided convection-enhanced delivery. This approach involves surgical exposure of the brain tissue, and insertion of small diameter catheters into the injected structures. Injection usually takes long time periods (several hours) and a pressure gradient in order to saturate the targeted tissues. Even with these techniques, there is limited tissue distribution after injection. In non-human models both the vector and huntingtin lowering have been demonstrated to be present in distant structures, such as the cortex. It is unclear whether this occurs via axonal transport or by some other mechanism such as secretion and absorption of miRNA-containing exosomes.

This is a challenging trial using a novel therapeutic approach. The community will be looking forward to learning more about the feasibility of the approach, its safety, and efficacy.

KINECT-HD (NCT04102579)

Study title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease [2].

Intervention: Once daily valbenazine, [9] a VMAT2 inhibitor.

Description: The KINECT-HD trial, sponsored by Neurocrine Biosciences and the Huntington Study Group, aims to evaluate the efficacy, safety and tolerability of valbenazine in adults (18 to 75 years of age) with a clinical diagnosis of HD with chorea, compared with placebo. The purpose is to assess whether valbenazine is more effective than placebo in reducing chorea associated with HD.

Individuals with the following are not eligible: a history of prior VMAT2 inhibitor therapy; swallowing difficulties; who are pregnant or breastfeeding; or with a history of long QT syndrome, cardiac tachyarrhythmia, left bundle-branch block, atrioventricular block, bradycardia or hear failure; unstable or serious medical or psychiatric illness; significant suicidal risk; substance dependence or abuse; unstable antidepressant regimen; previous history of gene therapy; receiving an investigational drug within 30 days of baseline visit; and blood donation or significant blood loss (≥550 mL) within 30 days of baseline visit.

KINECT-HD is an international, multi-centre, randomized, double-blind, controlled, parallel phase 3 trial. It has 2 study arms: the active group, where participants will receive valbenazine once daily up to 80 mg based on tolerability for 12 weeks; and the comparator group, where participants will receive a placebo capsule once daily for 12 weeks.

The study will last around 15 weeks, with an 8-week dose adjustment (i.e. 40 mg > 60 mg > 80 mg) based on tolerability followed by 4 weeks of dose maintenance, and will enrol 120 participants equally distributed across groups. Recruitment is currently ongoing, and approximately 55 centres across the US and Canada will be involved.

The primary outcome measure is change in chorea at 12 weeks measured as a sum of the chorea items of the UHDRS Total Motor Score. Secondary outcomes include subjective impression of change; quality of life and digital biomarkers.

Sponsors/funders: Neurocrine Biosciences and the Huntington Study Group.

Comments: Valbenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor previously approved by FDA for tardive dyskinesia. It is a prodrug of dihydrotetrabenazine that reduces dopamine release into the synaptic cleft by selectively inhibiting pre-synaptic VMAT2.

There are two other VMAT2 inhibitors on the market: tetrabenazine (3-times daily) and deutatrabenazine (twice-daily), both of them approved by FDA for chorea associated with HD. Apart from dosage regimen, it is unclear if there are differences between these two modestly effective drugs, which have comparable safety profiles with risks of suicidality, parkinsonism and QT prolongation [10–12].

Currently, valbenazine is FDA-approved for tardive dyskinesia (40 mg daily for one week followed by 80 mg daily thereafter) and has had an unsuccessful trial in paediatric Tourette’s syndrome.

Conflicts of interest

FBR and EJW were sub-investigators on LEGATO-HD (NCT02215616), IONIS HTTRx (NCT02519036) and IONIS HTTRx OLE (NCT03342053), are sub-investigators on the Roche GENERATION-HD (NCT03761849), Roche Natural History Study (NCT03664804) and Roche GEN-EXTEND (NCT03842969) trials, and EJW was a sub-investigator on the Amaryllis (NCT02197130). EJW is the chief investigator of the Roche GEN-PEAK trial (NCT04000594) and FBR is a sub-investigator. The authors did not make use of confidential or privileged information: all materials included in this manuscript were collected from publicly available sources. FBR has provided consultancy services to GLG. EJW has participated in scientific advisory boards with Hoffmann-La Roche Ltd, Ionis, Shire, GSK, Wave Life Sciences, PTC Therapeutics, Takeda and Mitoconix. All honoraria were paid through UCL Consultants Ltd, a wholly owned subsidiary of UCL. Their Host Institution, University College London Hospitals NHS Foundation Trust, has received funds as compensation for conducting clinical trials for Ionis Pharmaceuticals, Pfizer and Teva Pharmaceuticals. Hoffman La Roche Ltd has supported UCL with research funding for EJW.

ACKNOWLEDGMENTS

The authors are supported by CHDI Foundation, Inc. (salary support to FBR and EJW for conduct of the HDClarity study).

REFERENCES

[1] 

UniQure Biopharma B.V. Safety and Proof-of-Concept (POC) Study With AMT-130 in Adults With Early Manifest Huntington Disease. https://ClinicalTrials.gov/show/NCT04120493; 2019.

[2] 

Neurocrine Biosciences, Huntington Study Group. Efficacy, Safety, and Tolerability of Valbenazine for the Treatment of Chorea Associated With Huntington Disease. https://ClinicalTrials.gov/show/NCT04102579; 2019.

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Wave Life Sciences Ltd. Safety and Tolerability of WVE-120102 in Patients With Huntington’s Disease. https://ClinicalTrials.gov/show/NCT03225846; 2017.

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Wave Life Sciences Ltd. Safety and Tolerability of WVE-120101 in Patients With Huntington’s Disease. https://ClinicalTrials.gov/show/NCT03225833; 2017.

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Wave Life Sciences Announces Topline Data and Addition of Higher Dose Cohort in Ongoing Phase 1b/2a PRECISION-HD2 Trial in Huntington’s Disease [press release]. 2019.

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Claassen DO , Carroll B , De Boer LM , Wu E , Ayyagari R , Gandhi S , et al. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. J Clin Mov Disord, 2017;4:3.

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