Ipsen announces late-breaking data from first head-to-head study comparing Dysport® and Botox® in adults with upper limb spasticity

• Phase IV head-to-head, double-blind trial comparing safety and efficacy met its primary and secondary endpoints
• The DIRECTION trial results show the safety profile for Dysport^® (abobotulinumtoxinA) was non-inferior to Botox^® (onabotulinumtoxinA) in adult patients with upper limb spasticity
• Patients treated with Dysport in the DIRECTION trial achieved a longer duration of response than patients treated with Botox
• Data will be presented at a late-breaking session at the ISPRM congress¹

PARIS, FRANCE – 19 MAY 2026 – Ipsen (Euronext: IPN; ADR: IPSEY) announced today results from the only prospective, head-to-head Phase IV DIRECTION trial comparing Dysport^® (abobotulinumtoxinA) to Botox^® (onabotulinumtoxinA) in adults living with upper limb spasticity (ULS)¹ will be presented as a late-breaking presentation at the International Society of Physical and Rehabilitation Medicine (ISPRM) world congress in Vancouver on May 19, 2026. The trial showed that patients treated with Dysport had a non-inferior safety profile to Botox and achieved longer-lasting symptom control (based on a pre-specified 80% confidence interval)¹.

The DIRECTION trial addresses decades-long evidence gaps by delivering the first head-to-head, double-blind, comparative data between Dysport and Botox in adult spasticity. More broadly, these findings reinforce published real-world experience demonstrating that Dysport delivers durable results for patients with ULS in routine practice².

“Ipsen is committed to generating robust clinical evidence that supports scientific understanding and real-world practice. In spasticity, the durability of treatment response plays a critical role in patients’ function, mobility and quality of life,” said Sandra Silvestri, PhD, MD, Chief Medical Officer, Ipsen. “The DIRECTION data provides further support that Dysport can delay breakthrough symptoms with a well-established safety profile.”

For the primary endpoint of the trial, Dysport demonstrated non-inferiority compared with Botox with a treatment-emergent adverse event rate of 20.3% vs 23.0%, respectively (adjusted difference (aboBoNT-A – onaBoNT-A) was −2.7% (80%CI: −6.2%, 0.9%)¹. The results support the well-established safety profiles of these treatments.

In addition, the secondary efficacy endpoint was met: patients treated with Dysport experienced a longer duration of effect compared with those treated with Botox (14.2 vs 13.8 weeks, respectively; adjusted difference favoring Dysport (80%CI: 0.2, 5.9) with a pre-specified significance threshold for statistical significance (p=0.17; significance threshold, p=0.20).

Evidence of longer duration was consistent across most demographic and clinical subgroups¹ which is important as published research shows that over 80% of patients experience breakthrough symptoms between injection cycles and more than 70% of patients express a need for longer lasting treatment³.

“Today, for the first time, we have comparative evidence that distinguishes the performance of two widely used botulinum toxin treatments in patients with spasticity,” said Dr. Alberto Esquenazi, DIRECTION Principal Investigator. “These findings are based on a rigorously controlled study design and contribute meaningful data for clinicians, strengthening the evidence available for the use of botulinum toxin therapies in people with spasticity.”

About DIRECTION (NCT04936542)
DIRECTION is the first ever spasticity trial to compare Dysport^® (abobotulinumtoxinA) and Botox^® (onabotulinumtoxinA) directly in adults with upper limb spasticity. It is a Phase IV, randomized, double-blind, crossover trial involving 464 people living with upper limb spasticity at 72 sites across the USA, France, and Canada. Patients in the trial had an average age of 57 years, two-thirds were male, and most patients had spasticity because of a stroke.

Each participant received one treatment cycle with each toxin, administered using standardized, instrument-guided techniques to ensure fairness and comparability. The trial used a rigorous design, controlling for factors that could affect treatment outcomes including volume, dilution, dose, muscles treated, and the use of guidance. The trial was powered to detect differences in safety (primary endpoint), duration of response (a key secondary endpoint) and functional outcomes.

About Adult Upper Limb Spasticity
Upper limb spasticity (ULS) can significantly impair function, mobility, and quality of life. Botulinum toxin type A injections are a recommended first-line treatment. Many patients express frustration with waning treatment effect before their next scheduled injection, impacting daily function and increasing caregiver burden².

About Dysport
Dysport^® (abobotulinumtoxinA) is an injectable form of a botulinum neurotoxin type A (BoNT-A) product, which is a substance derived from Clostridium bacteria producing BoNT-A that inhibits the effective transmission of nerve impulses and thereby reduces muscular contractions. It is supplied as a lyophilized powder. AbobotulinumtoxinA has marketing authorization in approximately 90 countries, more than 30 years of clinical experience and >18 million treatment years of patient experience.

The detailed recommendations for the use of Dysport^® are described in the Summary of Product Characteristics (SmPC) for Dysport (300 units) Powder and Dysport (500 units) Powder, and the U.S. Prescribing Information (PI).

NOTE: Dysport^® labels, approved indications and dilutions may vary from country to country and from the DIRECTION methodology.

About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by internal and external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries.

Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.

Ipsen Contacts
Investors
Henry Wheeler	henry.wheeler@ipsen.com	+33 7 66 47 11 49
Khalid Deojee	khalid.deojee@ipsen.com	+33 6 66 01 95 26
Media
Sally Bain	sally.bain@ipsen.com	+1 857 320 0517
Anne Liontas	anne.liontas.ext@ipsen.com	+33 7 67 34 72 96

References

1. Esquenazi A. A randomized, double-blind, head-to-head, crossover study comparing the clinical safety and efficacy of abobotulinumtoxina with onabotulinumtoxina when treating adults with upper limb spasticity. Presented at: International Society of Physical and Rehabilitation Medicine (ISPRM) World Congress; 2026 May 20; Vancouver, Canada.
2. Turner-Stokes L et al. J Rehabil Med. 2021;53:jrm00157 
3. Jacinto J et al. Front Neurol. 2020;11:388.
   
   

Disclaimers and/or forward-looking statements
The forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation and risks arising from unexpected regulatory or political changes such as changes in tax regulation and regulations on trade and tariffs, such as protectionist measures, especially in the United States; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com.

Attachment

• Ipsen_PR_Direction Study at ISPRM_190526