votoplam (PTC518) / PTC Therap, Novartis - LARVOL DELTA

PTCT Stock Dips 18% Despite Positive Huntington's Disease Study Results (Gurufocus) - "PTC Therapeutics (PTCT, Financial) Phase 2 trial shows potential, but stocks fall by nearly 19%. Analysts set a one-year average price target of $63.21, suggesting significant upside potential."

Stock price • Huntington's Disease

PTC518 PIVOT-HD Study Achieves Primary Endpoint (PTC Therapeutics Press Release) - P2 | N=252 | PIVOT-HD (NCT05358717) | Sponsor: PTC Therapeutics | "Results from the full 12-month cohort demonstrate dose-dependent lowering in blood HTT levels, with 23% at the 5mg dose level for both Stage 2 and 3 patients and 39% and 36% at the 10mg dose level for Stage 2 and 3 patients, respectively. For Stage 2 patients, there were dose-dependent trends of benefit on clinical scales including the Composite Unified Huntington's Disease Rating Scale (cUHDRS) and Total Motor Score (TMS) subscale. For Stage 3 patients, there were trends favoring the 5mg dose group relative to placebo, but not the 10mg dose group, suggesting that treatment effect may differ in Stage 3 patients relative to Stage 2 patients...In addition, 24-month treatment data from the patients on whom data were shared last year (N=21) demonstrate signals of dose-dependent trends on the cUHDRS....PTC will hold a conference call at 8:00 am ET today to discuss this news."

P2 data • Huntington's Disease

PTC shares jump on FDA fast-track hopes after Huntington's drug hits mark (Firstwordpharma Press Release) - "PTC Therapeutics said its experimental Huntington's disease treatment PTC518 (votoplam) achieved the primary endpoint in a mid-stage study, sending shares up nearly 22% Monday."

Commercial • Huntington's Disease

PTC Therapeutics Provides Corporate Update and Reports Fourth Quarter and Full Year 2024 Financial Results (PRNewswire) - "PTC submitted four regulatory approval applications to FDA in 2024....Sepiapterin for children and adults with PKU, with a target regulatory action date of July 29, 2025....PTC submitted several additional marketing authorization applications outside the U.S. for sepiapterin in 2024, with CHMP opinion on sepiapterin MAA expected in Q2 2025 and a regulatory decision in Japan expected in Q4 2025....12-month results from the PIVOT-HD Phase 2 study of PTC518 expected in Q2 2025."

CHMP • Japan approval • P2 data • PDUFA • Huntington's Disease • Phenylketonuria

Huntington's Disease Clinical Trials Update: September 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing extension study of PTC518 from PTC Therapeutics, including 12-month interim results from the parent study. We also discuss 24-month interim results from uniQure's AMT-130 program and 28-week follow-up results from Wave Life Sciences' SELECT-HD clinical trial of WVE-003. Additionally, we provide a comprehensive listing of all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Review • Huntington's Disease • Movement Disorders

PTC Therapeutics Provides Update on Commercial Performance and R&D Pipeline at 43rd Annual J.P. Morgan Healthcare Conference (PRNewswire) - "PTC signed a global license and collaboration agreement with Novartis for the research, development and commercialization of PTC518 for HD, which has now closed. Key aspects of the transaction include the following: PTC to receive $1.0 billion in upfront proceeds following closing. PTC is eligible to receive up to $1.9 billion in development, regulatory and sales milestones. PTC to receive 40% profit share on U.S. sales, and double-digit tiered royalties on ex-U.S. sales. Novartis will assume global development, manufacturing and commercial responsibilities following the completion of the placebo-controlled portion of PIVOT-HD, which is expected in 1H 2025."

Licensing / partnership • Trial completion date • CNS Disorders • Huntington's Disease

PTC Therapeutics Enters into a Global License and Collaboration Agreement with Novartis for PTC518 Huntington's Disease Program (PRNewswire) - "PTC Therapeutics, Inc...announced today the signing of an exclusive global license and collaboration agreement with Novartis Pharmaceuticals Corporation...for its PTC518 Huntington's disease program, which includes related molecules. Under the agreement, PTC will receive an upfront payment of $1.0 billion, up to $1.9 billion in development, regulatory and sales milestones, a profit share in the U.S., and double-digit tiered royalties on ex-U.S. sales...Novartis will assume responsibility for PTC518's development, manufacturing and commercialization, following the completion of the on-going placebo-controlled portion of PIVOT-HD, which is expected to occur in H1 2025...The parties anticipate that the agreement will close in the first quarter of 2025."

Licensing / partnership • Trial completion • CNS Disorders • Huntington's Disease

Twelve-Month Interim Data from PIVOT-HD: a Phase 2, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of PTC518 in Participants with Huntington's Disease (HSG 2024) - P2 | "These interim results continue to demonstrate that PTC518 is a potential therapeutic benefit in patients with HD."

Clinical • P2 data • Huntington's Disease • Movement Disorders • NEFL • Plasma NfL

PIVOT-LTE: a Phase 2, Double-Blind, Randomized Extension Study to Evaluate the Long-Term Safety and Efficacy of PTC518 in Participants with Huntington's Disease (HSG 2024) - P2 | "Early data from PIVOT-HD indicate PTC518 treatment saw a dose-dependent reduction of mHTT in blood and CSF and was well tolerated. Enrollment of participants for PIVOT-LTE is ongoing and data will be presented at a later timepoint."

Clinical • P2 data • Huntington's Disease • Movement Disorders

PIVOT-HD: A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=252 | Active, not recruiting | Sponsor: PTC Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Aug 2025 | Trial primary completion date: Mar 2024 ➔ Feb 2025

Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

FDA Grants Fast Track Designation to PTC518 Huntington’s Disease Program (PRNewswire) - "PTC Therapeutics...announced today that the FDA has granted Fast Track designation to the PTC518 program for the treatment of Huntington's disease...'The granting of Fast Track designation to the PTC518 program further supports the potential of PTC518 to provide a disease modifying therapy to Huntington's disease patients'...'We look forward to working collaboratively with FDA to continue to advance the program as efficiently as possible.'"

Fast track • CNS Disorders • Huntington's Disease

Pharmacokinetics and pharmacodynamics of PTC518, an oral huntingtin lowering splicing modifier: A first-in-human study. (PubMed, Br J Clin Pharmacol) - "PTC518 was well tolerated, and proof of mechanism of this novel splicing modifier was demonstrated by the dose-dependent decrease in systemic HTT mRNA and HTT protein levels. Results from this first-in-human study support further studies in patients with HD and demonstrate the potential for PTC518 as a breakthrough treatment for HD."

Journal • P1 data • PK/PD data • Genetic Disorders • Huntington's Disease • Movement Disorders

An Extension Study to Evaluate the Long-Term Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=250 | Enrolling by invitation | Sponsor: PTC Therapeutics | Recruiting ➔ Enrolling by invitation

Enrollment status • Genetic Disorders • Huntington's Disease • Movement Disorders

Interim PIVOT-HD Results Demonstrate Evidence of Favorable CNS Biomarker and Clinical Effects at Month 12 in Huntington's Disease Patients (PRNewswire) - P2a | N=252 | PIVOT-HD (NCT05358717) | Sponsor: PTC Therapeutics | "PTC Therapeutics, Inc...today shared interim results from the Phase 2 PIVOT-HD study of PTC518 in Huntington's disease (HD) patients...Furthermore, following 12 months of treatment, PTC518 continues to be safe and well tolerated...At Month 12, durability of dose-dependent mHTT lowering in the blood was demonstrated with lowering of 22% and 43% for 5mg and 10mg dose levels, respectively. In the CSF, dose dependent mHTT lowering was also demonstrated with lowering of 21% and 43%, for 5mg and 10mg dose levels, respectively...In addition, PTC announced that the FDA has lifted the partial clinical hold on the program based on review of the PIVOT-HD data."

FDA event • P2a data • CNS Disorders • Huntington's Disease

Understanding Pharmacy Costs and the Changing Treatment Landscape in Huntington's Disease (HD) in the US: A Systematic Literature Review (SLR) and Database Review for Disease-Modifying Therapies (DMT) in Development (ISPOR 2024) - "Motor symptoms incur the greatest annual drug cost, with high median costs per patient (2019) for tetrabenazine ($24,996), deutetrabenazine ($69,972), and valbenazine ($76,908). Ten clinical trials are investigating potential future DMTs: two-antisense oligonucleotides (n=5; Tominersen [RO7234292, ISIS 443139], WVE-003), two-RNA-targeting small molecules (n=2; PTC518, Branaplam), monoclonal antibodies (n=2; ANX005, VX15/2503), and gene therapy (n=1; rAAV5-miHTT). Pharmacy costs for symptomatic treatment are substantial in HD, with these costs increasing as HD progresses and symptom severity increases. This significant burden illustrates the importance of developing new DMTs that can prevent or slow disease progression for patients with HD."

Review • CNS Disorders • Depression • Gene Therapies • Huntington's Disease • Mood Disorders • Movement Disorders • Psychiatry

Huntington's Disease Clinical Trials Update: February 2024. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the ongoing program from VICO Therapeutics and on the recently terminated VIBRANT-HD clinical trials. We also discuss updates from uniQure's AMT-130 program and PTC therapeutics' trial of PTC518 and list all currently registered and ongoing clinical trials in Huntington's disease."

Journal • Genetic Disorders • Huntington's Disease • Movement Disorders

An Extension Study to Evaluate the Long-Term Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: PTC Therapeutics

New P2 trial • Genetic Disorders • Huntington's Disease • Movement Disorders

PTC Therapeutics Provides an Update on Commercial Progress and R&D Pipeline at 42nd Annual J.P. Morgan Healthcare Conference (BioSpace) - "Results from 12-month interim data from the PIVOT-HD trial of PTC518 in HD patients are expected in the second quarter."

P2 data • CNS Disorders • Huntington's Disease

A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2 | N=252 | Recruiting | Sponsor: PTC Therapeutics | Phase classification: P2a ➔ P2

Phase classification • Genetic Disorders • Huntington's Disease • Movement Disorders

Evaluation of a small molecule splicing modulator in a humanized HTT intron 49 mouse (Neuroscience 2023) - "Evaluation of a small molecule splicing modulator in a humanized HTT intron 49 mouse Magnani, Dario1*; Kritikou, Eva1; Mota, Daniel1; Macabuag, Natsuko1, Herva Moyano, Maria1; Mitchell, Phil1; Fischer, David F. 1; Liu,Longbin2 , Kheterpal, Vinod2; McAllister, George2; Chen, Richard21 Charles River, 2 CHDI Management Inc./CHDI Foundation, *presenting authorLowering the expression of the pathogenic mutant huntingtin (mHTT) mRNA and protein is a leading therapeutic approach for the treatment of Huntington's Disease (HD).Branaplam (LMI070) and PTC-518 are small molecule drugs that target splicing of the exon junction 49-50 of HTT pre-mRNA, promoting the retention of a pseudo-exon within intron 49, causing the degradation of HTT mRNA by nonsense-mediated decay, and consequential decrease in protein levels.Both drugs recently proceeded to Phase 2 clinical evaluation. Q175 knock-in mice, which carry a human HTT Exon 1 with approximately 190 CAGs knocked into the murine Htt..."

Preclinical • CNS Disorders • Pain

A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2a | N=252 | Recruiting | Sponsor: PTC Therapeutics | N=162 ➔ 252 | Trial primary completion date: Jun 2023 ➔ Mar 2024

Enrollment change • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

PTC Therapeutics Shares Positive Interim Data from PIVOT-HD Clinical Trial in Huntington’s Disease Patients (PRNewswire) - P2a | N=162 | PIVOT-HD (NCT05358717) | Sponsor: PTC Therapeutics | "PTC Therapeutics...today shared interim data from the 12-week portion of the PIVOT-HD Phase 2 study of PTC518 in Huntington's disease (HD) patients. The study demonstrated dose-dependent lowering of Huntingtin (HTT) protein levels in peripheral blood cells, reaching a mean 30% reduction in mutant HTT levels at the 10mg dose level. In addition, PTC518 exposure in the cerebrospinal fluid (CSF) was consistent with or higher than plasma unbound drug levels."

P2a data • CNS Disorders • Huntington's Disease

A Study to Evaluate the Safety and Efficacy of PTC518 in Participants With Huntington's Disease (HD) (clinicaltrials.gov) - P2a | N=162 | Recruiting | Sponsor: PTC Therapeutics | Trial completion date: Mar 2024 ➔ Jul 2024 | Trial primary completion date: Mar 2023 ➔ Jun 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Huntington's Disease • Movement Disorders

PTC Previews Key Spring Readouts in Full-Year 2022 Report (BioSpace) - “The company also expects to complete enrollment in the Phase II PIVOT-HD trial of PCT518 in Huntington’s disease. Data from the first 12 weeks of PIVOT-HD are also expected to roll in during the second quarter of 2023, Peltz said.”

P2 data • CNS Disorders • Huntington's Disease

Huntington's Disease Clinical Trials Corner: November 2022. (PubMed, J Huntingtons Dis) - " In this edition of the Huntington's Disease Clinical Trials Corner, we expand on the PIVOT HD (PTC518), and SIGNAL (pepinemab) trials, and list all currently registered and ongoing clinical trials in Huntington's disease.We also introduce a 'breaking news' section highlighting recent updates about the SELECT HD, uniQure AMT-130, and VIBRANT HD clinical trials."

Journal • Genetic Disorders • Huntington's Disease • Movement Disorders