For adults with spasticity or cervical dystonia How long does your patients symptom * relief last?

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1 For adults with spasticity or cervical dystonia How long does your patients symptom * relief last? Consider Dysport because a long duration of response should matter 1 In clinical trials, retreatment was between 12 and 16 weeks or longer Repeat Dysport treatment should be administered when the effect of a previous injection has diminished, but no sooner than 12 weeks after the previous injection The degree and pattern of muscle spasticity at the time of reinjection may necessitate alterations in the dose of Dysport and muscles to be injected * Symptoms of spasticity can include abnormal increase in muscle tone and muscle spasm. INDICATIONS Dysport (abobotulinumtoxina) for injection is indicated for the treatment of: Spasticity in adult patients Adults with cervical dystonia Lower limb spasticity in pediatric patients 2 years of age or older The safety and effectiveness of Dysport injected into upper limb muscles or proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established. Safety and effectiveness in pediatric patients with lower limb spasticity below 2 years of age have not been evaluated. Safety and effectiveness in pediatric patients with cervical dystonia or upper limb spasticity have not been established. IMPORTANT SAFETY INFORMATION Warning: Distant Spread of Toxin Effect Postmarketing reports indicate that the effects of Dysport and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including upper limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to lower than the maximum recommended total dose. Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information. It s Time

2 Dysport is a proven first-line treatment option1 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

3 Approved for three therapeutic indications: About Dysport ADULT SPASTICITY 1 Upper limb (ULS) 2015 Lower limb (LLS) added in 2017 ADULT CERVICAL DYSTONIA 1 (CD) 9 PEDIATRIC LOWER LIMB SPASTICITY (PLLS) (2 YEARS OF AGE AND OLDER) Dysport (abobotulinumtoxina) is the only botulinum toxin FDA approved for the treatment of lower limb spasticity in children aged two and older 1 According to the American Academy of Neurology 2016 Summary of Practice Guideline Update for Clinicians, Dysport is considered effective and should be offered (evidence Level A*) in all 3 of the following conditions 2 : Adult upper extremity spasticity Adult lower extremity spasticity Adult cervical dystonia *Evidence Level A: Established for the given condition in the specified population. Level A rating requires at least two consistent Class I studies (randomized, controlled clinical trials of the intervention of interest with masked or objective outcome assessment, in a representative population. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences). 3 IMPORTANT SAFETY INFORMATION (continued) Contraindications Dysport is contraindicated in patients with known hypersensitivity to any botulinum toxin preparation or to any of the components; or in the presence of infection at the proposed injection site(s); or in patients known to be allergic to cow s milk protein. Hypersensitivity reactions including anaphylaxis have been reported. Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information. It s Time 3

4 Dysport : Proven efficacy in adult spasticity UPPER LIMB SPASTICITY Dysport 500 Units and Dysport 1,000 Units significantly reduced muscle tone in primary target muscle group (PTMG) 1,4 REDUCTION FROM BASELINE IN MUSCLE TONE AS MEASURED BY MODIFIED ASHWORTH SCALE (MAS) AT WEEK Dysport 1,000 Units (n=79) Dysport 500 Units (n=80) Least squares (LS) mean change in MAS from baseline in the intent-to-treat (ITT) population * -1.2* Improvement Placebo (n=79) *P 0.05 vs placebo Study design: The efficacy and safety of Dysport (abobotulinumtoxina) were evaluated in a randomized, multi-center, double-blind, placebo-controlled study in 238 adults with upper limb spasticity. The co-primary efficacy endpoints were mean change in MAS score in the PTMG (elbow, wrist, and finger flexors) and PGA of response to treatment between baseline and Week 4. MAS score at baseline (mean [SD]): placebo, 3.9 (0.4); Dysport 500 Units, 3.9 (0.5); Dysport 1,000 Units, 3.9 (0.4). Follow-up assessments occurred at Weeks 1, 4, and 12; visits were also permitted at Weeks 16, 20, and 24 as needed for retreatment. After 3 months of on-study treatment, patients were given the opportunity to continue open-label treatment with Dysport for up to 5 additional treatment cycles Clinical improvement may be expected 1 week after administration of Dysport LS mean change from baseline at Week 1: Dysport 1,000 Units, -0.9 (P 0.05 vs placebo); Dysport 500 Units, -0.8 (P 0.05 vs placebo); placebo, -0.2 Physicians reported a significant (P 0.05) improvement in response to treatment in patients receiving either dose of Dysport at Week 4, as assessed by the Physician s Global Assessment (PGA) of response to treatment (co-primary efficacy endpoint) Dysport 1,000 Units: 1.8 Dysport 500 Units: 1.4 Placebo: 0.7 ~45 of all patients were naive ~55 had prior botulinum toxin to botulinum toxin 4 experience 4 Calculations were based on the number of patients responding at each week divided by the total number of patients at Week 4. Defined as a subject who had never received any botulinum toxin in the affected upper limb. 4 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

5 Efficacy: Adult Spasticity LOWER LIMB SPASTICITY Dysport 1,500 Units significantly reduced muscle tone at affected ankle joint 1,4 REDUCTION FROM BASELINE IN MUSCLE TONE AS MEASURED BY MODIFIED ASHWORTH SCALE (MAS) AT WEEK 4 0 Dysport 1,500 Units (n=128) Least squares (LS) mean change in MAS from baseline in the intent-to-treat (ITT) population Improvement Dysport 1,000 Units (n=125) Placebo (n=128) P<0.05 vs placebo Study design: The efficacy of Dysport (abobotulinumtoxina) was evaluated in a randomized, multi-center, double-blind, placebo-controlled study in 381 adults with lower limb spasticity. The primary efficacy endpoint was muscle tone assessed by LS mean change from baseline in MAS score at the affected ankle joint at Week 4. MAS score at baseline (mean [SD]): placebo, 3.9 (0.5); Dysport 1,000 Units, 3.8 (0.5); Dysport 1,500 Units, 3.7 (0.5). Follow-up assessments occurred at Weeks 1, 4, and 12; visits were also permitted at Weeks 16, 20, and 24 as needed for retreatment. After 3 months of on-study treatment, patients were given the opportunity to continue open-label treatment with Dysport. ~64 of all patients were naive ~36 had prior botulinum toxin to botulinum toxin 4 experience 4 Defined as a subject who had never received any botulinum toxin in the affected lower limb. IMPORTANT SAFETY INFORMATION (continued) Warnings and Precautions Lack of Interchangeability Between Botulinum Toxin Products The potency Units of Dysport are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products, and, therefore, units of biological activity of Dysport cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method. It s Time 5

6 Safety results in 391 adult Dysport treated patients with upper limb spasticity UPPER LIMB SPASTICITY In adults with doses of up to Dysport 1,000 Units 1 Most common adverse reactions observed in 2 of adults with upper limb spasticity and reported more frequently than with placebo* Adverse Reactions Infections and infestations Dysport 500 Units (n=197) Dysport 1,000 Units (n=194) Nasopharyngitis Urinary tract infection Influenza Infection Musculoskeletal and connective tissue disorders Muscular weakness Pain in extremity Musculoskeletal pain Back pain Nervous system disorders Headache Dizziness Convulsion Syncope Placebo (n=279) Hypoaesthesia 0 2 <1 Partial seizures General disorders and administration site conditions Fatigue Asthenia 2 1 <1 Injury, poisoning, and procedural complications Fall Injury Contusion 1 2 <1 Gastrointestinal disorders Diarrhea 1 2 <1 Nausea Constipation Investigation Blood triglycerides increased Respiratory, thoracic, and mediastinal disorders Cough Vascular disorders Hypertension 1 2 <1 Psychiatric disorders Depression *Data from pooled, double-blind trials of adults with ULS. 6 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

7 Safety results in 255 adult Dysport treated patients with lower limb spasticity LOWER LIMB SPASTICITY In adults with doses of up to Dysport 1,500 Units 1 Adverse reactions observed in 2 of adults with lower limb spasticity and reported more frequently than with placebo Safety: Adult Spasticity Adverse Reactions Musculoskeletal and connective tissue disorders Dysport 1,000 Units (n=127) Dysport 1,500 Units (n=128) Muscular weakness Pain in extremity Arthralgia Back pain Injury, poisoning, and procedural complications Fall Contusion Wrist fracture Nervous system disorders Headache Epilepsy/Convulsion/Partial seizure/status epilepticus Infections and infestations Upper respiratory tract infection General disorders and administration site conditions Fatigue Asthenia Influenza-like illness Edema peripheral Investigations Alanine aminotransferase increased Gastrointestinal disorders Constipation Dysphagia Psychiatric disorders Depression Insomnia Vascular disorders Hypertension Placebo (n=130) In the efficacy and safety studies of Dysport for the treatment of lower limb spasticity in adults, muscular weakness was reported more frequently in women (10) treated with Dysport 1,500 Units compared to men (5). Falls were reported more frequently in patients 65 years of age and over. Data from double-blind trial of adults with LLS. It s Time 7

8 Dysport : Proven efficacy in adult cervical dystonia CERVICAL DYSTONIA Dysport significantly reduced abnormal head position at Week 4 1,4-6 IMPROVEMENT FROM BASELINE AT WEEK 4 IN ABNORMAL HEAD POSITION AS MEASURED BY REDUCTION IN TORONTO WESTERN SPASMODIC TORTICOLLIS RATING SCALE (TWSTRS) TOTAL SCORE Adjusted mean TWSTRS total score in the ITT population STUDY 1 Week 4 (Primary endpoint) -15.6* * Week Improvement STUDY 2 Week 4 (Primary endpoint) (n=51) (n=58) (n=46) (n=46) (n=37) (n=42) -9.6* -3.7 (n=22) -7.5* Week 8 Dysport 500 Units Placebo -1.7 (n=15) *P<0.05 vs placebo Design for Studies 1 and 2: The efficacy of Dysport (abobotulinumtoxina) was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter, parallel-group, single-dose studies with a 12-week follow-up in patients with cervical dystonia (Dysport, n=121; placebo, n=131). Patients could switch to open-label extension studies after Week 4. Dysport 500 Units was given by intramuscular injection, divided among 2 to 4 affected muscles. The primary efficacy endpoint was based on the total TWSTRS change from baseline at Week 4 for both studies. TWSTRS total score (maximum: 85 points) is composed of 3 subscales (Severity, Disability, and Pain). For Study 1, the mean TWSTRS total score at baseline was 46 for placebo and 44 for Dysport 500 Units. For Study 2, the mean TWSTRS total score at baseline was 46 for placebo and 45 for Dysport 500 Units. 17 of all patients in Study 1 and of all patients in Study 2 in Study 1 and 74 in Study 2 had prior botulinum toxin experience 4 Defined as not previously treated with a botulinum toxin for the treatment of cervical dystonia. 8 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

9 Dysport significantly reduced neck pain at Week 4 4,6 REDUCTION FROM BASELINE IN PAIN SEVERITY FOLLOWING 1 TREATMENT DOSE Change from baseline in mean patient Visual Analogue Pain Scale (VAS-Pain) (mm) Baseline n=43 n=37 Week 4 Week 8 n=43 Significant reduction n=37 P=0.024 n=15 n=22 P=0.025 Pain relief Dysport 500 Units Placebo Efficacy: Adult Cervical Dystonia -15 See prior page for study design. On a 100-point scale (0 [no symptoms] to 100 mm [worst possible symptoms]), baseline VAS score (patient self-rated) was 48.6 in the Dysport (abobotulinumtoxina) group and 52.9 in the placebo-controlled group. Secondary efficacy endpoint was change in patient Visual Analogue Pain Scale (VAS-Pain) at Week 4 compared with baseline. IMPORTANT SAFETY INFORMATION (continued) Warnings and Precautions (continued) Dysphagia and Breathing Difficulties Treatment with Dysport and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant side effects occur, additional respiratory muscles may be involved (see Boxed Warning). Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several weeks, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin. It s Time 9

10 Safety results in 173 adult Dysport treated patients with cervical dystonia CERVICAL DYSTONIA In adults with doses of up to Dysport 500 Units 1 Most common adverse reactions ( 5) and greater than placebo in the pooled, double-blind phase of clinical trials* Adverse Reactions Dysport 500 Units (n=173) Placebo (n=182) Any Adverse Reaction General disorders and administration site conditions Injection site discomfort 13 8 Fatigue Injection site pain 5 4 Musculoskeletal and connective tissue disorders Muscular weakness 16 4 Musculoskeletal pain 7 3 Gastrointestinal disorders Dysphagia 15 4 Dry mouth 13 7 Nervous system disorders Headache 11 9 Infections and infestations 13 9 Respiratory, thoracic, and mediastinal disorders 12 8 Dysphonia 6 2 Eye disorders 7 2 *Data from a single treatment cycle of Dysport 500 Units for adults with cervical dystonia. The following preferred terms were reported: vision blurred, diplopia, visual acuity reduced, eye pain, eyelid disorder, accommodation disorder, dry eye, eye pruritus. 10 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

11 IMPORTANT SAFETY INFORMATION (continued) Warnings and Precautions (continued) Pre-existing Neuromuscular Disorders Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of Dysport. Human Albumin and Transmission of Viral Diseases This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vcjd). There is a theoretical risk for transmission of Creutzfeldt- Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vcjd have ever been identified for licensed albumin or albumin contained in other licensed products. Intradermal Immune Reaction The possibility of an immune reaction when injected intradermally is unknown. The safety of Dysport for the treatment of hyperhidrosis has not been established. Dysport is approved only for intramuscular injection. Adverse reactions Most common adverse reactions ( 2 and greater than placebo in either Dysport group) in adults with upper limb spasticity for Dysport 500 Units, Dysport 1000 Units, and Placebo, respectively, were: nasopharyngitis (4, 1, 1), urinary tract infection (3, 1, 2), muscular weakness (2, 4, 1), musculoskeletal pain (3, 2, 2), dizziness (3, 1, 1), fall (2, 3, 2), and depression (2, 3, 1). Most common adverse reactions ( 5 and greater than placebo in either Dysport group) in adults with lower limb spasticity for Dysport 1000 Units, Dysport 1500 Units, and Placebo, respectively, were: falls (9, 6, 3), muscular weakness (2, 7, 3), and pain in extremity (6, 6, 2). Muscular weakness was reported more frequently in women (10) treated with 1500 units of Dysport compared to men (5). Safety: Adult Cervical Dystonia It s Time 11

12 For adults with spasticity Consider Dysport because a long duration of response should matter In clinical trials, retreatment was between weeks for the majority of patients; however, some patients had a longer duration of response 1,4 UPPER LIMB SPASTICITY* LOWER LIMB SPASTICITY* Weeks Weeks Patients needing retreatment per assessment () / / /147 Patients needing retreatment per assessment () / / /229 Week 12 Week 16 Week 20 Week 12 Week 16 Week 20 Time to retreatment was not the primary endpoint In the pivotal trials for adult spasticity, need for retreatment was determined by No longer demonstrating a decrease from baseline of 1 grade in MAS score in the primary targeted muscle group and No improvement in PGA (score 0) and No signs of unacceptable safety risk for next treatment cycle Investigator discretion (based on efficacy and safety criteria) determined need for retreatment for patients demonstrating a decrease from baseline of 1 grade in MAS score and/or improvement in PGA (i.e., a score +1) Some patients in clinical studies of spasticity had a longer duration of response, i.e. 20 weeks Repeat Dysport (abobotulinumtoxina) treatment should be administered no sooner than 12 weeks after the previous injection * Patients who remained in the study after Week 12 were permitted additional discretionary follow-up visits at Week 16, Week 20, and Week 24 to assess eligibility for retreatment. 12 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

13 For adults with cervical dystonia Consider Dysport because a long duration of response should matter ADULT CERVICAL DYSTONIA 1 Duration of response 12 WEEKS 14 WEEKS 18 WEEKS Median duration of response was 14 weeks 25 of patients receiving Dysport had a duration of response of at least 18 weeks Duration of Response In the pivotal trials for adult CD, need for retreatment was determined by change in TWSTRS total score returning to within 10 of baseline Repeat Dysport (abobotulinumtoxina) treatment should be administered no sooner than 12 weeks after the previous injection Follow-up assessments occurred at Weeks 2, 4, 8, and 12. After Week 4 of on-study treatment, patients were given the opportunity to continue open-label treatment with Dysport. IMPORTANT SAFETY INFORMATION (continued) Adverse reactions (continued) Most common adverse reactions ( 5 and greater than placebo) in adults with cervical dystonia for Dysport 500 Units and Placebo, respectively, were: muscular weakness (16, 4), dysphagia (15, 4), dry mouth (13, 7), injection site discomfort (13, 8), fatigue (12, 10), headache (11, 9), musculoskeletal pain (7, 3), dysphonia (6, 2), injection site pain (5, 4), and eye disorders (7, 2). It s Time 13

14 For pediatric patients aged 2 and older Dysport : Proven efficacy in lower limb spasticity PEDIATRIC LOWER LIMB SPASTICITY Significant results in both Dysport treatment groups vs placebo across co-primary efficacy endpoints at Week 4 1,4 Significant improvement in ankle plantar flexor muscle tone as determined by mean change in Modified Ashworth Scale (MAS) score at Week 4 Placebo: -0.5 Dysport 10 Units/kg/leg: -0.9* Dysport 15 Units/kg/leg: -1.0* Significant improvement in response to treatment as determined by mean Physician s Global Assessment (PGA) of response to treatment at Week 4 Placebo: 0.7 Dysport 10 Units/kg/leg: 1.5* Dysport 15 Units/kg/leg: 1.5* Study design: Efficacy evaluated in a double-blind, placebo-controlled study in 235 patients, 2 to 17 years of age, with lower limb spasticity due to cerebral palsy causing dynamic equinus foot deformity. Co-primary efficacy endpoints: mean change in MAS score in the ankle plantar flexor and mean PGA of response to treatment between baseline and Week 4. MAS score at baseline (mean [SD]): placebo, 3.2 (0.4); Dysport 10 Units/kg/leg, 3.1 (0.3); Dysport 15 Units/kg/leg, 3.1 (0.3). Investigator graded muscle tone on a 6-point scale: 0 (no increase in tone) to 4 (affected parts rigid in flexion or extension). Follow-up assessments at Weeks 4 and The majority of patients were retreated between weeks 35 Patients needing retreatment () (17/158) Week (53/158) Week (36/158) Week 22 However, some patients had a longer duration of response Patients who remained in the study after Week 12 were permitted additional discretionary follow-up visits at Week 16, Week 22, and Week 28 to assess eligibility for retreatment. The degree and pattern of muscle spasticity and the overall clinical benefit at the time of reinjection may necessitate alterations in the dose of Dysport (abobotulinumtoxina) and muscles to be injected Repeat Dysport treatment should be administered when the effect of a previous injection has diminished but no sooner than 12 weeks after the previous injection Eligibility for retreatment was assessed by the investigator at every visit from Week 12 onwards *P<0.05 vs placebo. IMPORTANT SAFETY INFORMATION (continued) Adverse reactions (continued) Most common adverse reactions ( 10 in any group and greater than placebo) in pediatric patients with lower limb spasticity for Dysport 10 Units/kg, 15 Units/kg, 20 Units/kg, or 30 Units/kg; and Placebo, respectively, were: upper respiratory tract infection (9, 20, 5, 10, 13), nasopharyngitis (9, 12, 16, 10, 5), influenza (0, 10, 14, 3, 8), pharyngitis (5, 0, 11, 3, 8), cough (7, 6, 14, 10, 6), and pyrexia (7, 12, 8, 7, 5). 14 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

15 Safety results in 160 Dysport treated pediatric patients with lower limb spasticity Adverse reactions observed in 4 of patients treated in the double-blind trial of pediatric patients with lower limb spasticity reported more frequently than with placebo 1 Unilateral Injections Bilateral Injections Adverse Reactions Infections and infestations Placebo (n=79) Dysport 10 Units/kg (n=43) Dysport 15 Units/kg (n=50) Dysport 20 Units/kg (n=37) Dysport 30 Units/kg (n=30) Nasopharyngitis Upper respiratory tract infection Influenza Pharyngitis Bronchitis Rhinitis Varicella Ear infection Respiratory tract infection viral Gastroenteritis viral Gastrointestinal disorders Vomiting Nausea Respiratory, thoracic, and mediastinal disorders Cough Oropharyngeal pain General disorders and administration site conditions Pyrexia Musculoskeletal and connective tissue disorders Pain in extremity Muscular weakness Nervous system disorders Convulsion/Epilepsy Pediatric Lower Limb Spasticity It s Time 15

16 For adults with spasticity Choose the appropriate dose in Dysport Units Dysport is not interchangeable with other botulinum toxins, and the potency units are not the same 1 Units of biological activity of Dysport (abobotulinumtoxina) cannot be compared to or converted into units of any other botulinum toxin products UPPER LIMB SPASTICITY Dosing for upper limb spasticity between Dysport 500 Units and Dysport 1,000 Units was divided among selected muscles at a given treatment session 1 Select dose based on muscles affected, severity of muscle spasticity, prior response, and adverse reaction history following treatment with Dysport 1 In ULS Common postures and muscles typically affected include 1,7 *: Flexed elbow Brachialis... Brachioradialis... Biceps brachii... Pronator teres... Recommended Dose Range in Dysport Units Clenched fist Flexor digitorum profundus... Flexor digitorum superficialis Flexed wrist Flexor carpi radialis... Flexor carpi ulnaris IMPORTANT SAFETY INFORMATION (continued) Drug Interactions Co-administration of Dysport and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of botulinum toxin may be potentiated. Use of anticholinergic drugs after administration of Dysport may potentiate systemic anticholinergic effects such as blurred vision. The effect of administering different botulinum neurotoxins at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by another administration of botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of Dysport. 16 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

17 Approved for use in 8 different muscles in adult ULS and 5 different muscles in adult LLS 1 LOWER LIMB SPASTICITY Dosing for lower limb spasticity between Dysport (abobotulinumtoxina) 1,000 Units and Dysport 1,500 Units was divided among selected muscles at a given treatment session 1 No more than 1 ml should generally be administered at any single injection site 1 The maximum recommended total dose (upper and lower limb combined) of Dysport for the treatment of spasticity in adults is Dysport 1,500 Units 1 In LLS Common postures and muscles typically affected include 1,8 *: Equinovarous foot Gastrocnemius: Medial head... Lateral head... Soleus... Tibialis posterior... Flexor digitorum longus... Flexor hallucis longus... Recommended Dose Range in Dysport Units Plantar flexed foot/ankle Gastrocnemius: Medial head... Lateral head... Soleus... Tibialis posterior... Flexor digitorum longus... Flexor hallucis longus Dosing: Adult Spasticity Flexed toes Flexor digitorum longus... Flexor hallucis longus *Not actual patients. It s Time 17

18 For adults with cervical dystonia Choose the appropriate dose in Dysport Units Dysport is not interchangeable with other botulinum toxins, and the potency units are not the same 1 Units of biological activity of Dysport (abobotulinumtoxina) cannot be compared to or converted into units of any other botulinum toxin products CERVICAL DYSTONIA In adult cervical dystonia, doses up to Dysport 1,000 Units (divided among affected muscles) injected intramuscularly, were systematically evaluated 1 The recommended initial dose is Dysport 500 Units given intramuscularly as a divided dose among affected muscles Titrate in 250-Unit steps according to patient s response In CD Common postures and muscles typically affected include 1,9 *: Dose Range in Dysport Units Anterocollis Sternocleidomastoid... Scalenus (medius/anterior) Retrocollis Levator scapulae Trapezius Longissimus Splenius capitis Semispinalis capitis *Not actual patients. Median dose: Dysport 125 Units. Dosing considerations for the sternocleidomastoid (SCM): Limiting the dose injected unilaterally into the SCM to Dysport 150 Units or less may reduce the occurrence of dysphagia. 18 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

19 Approved for use in 7 different muscles in adult CD 1 Select dose based on muscles affected, severity of muscle spasticity, prior response, and adverse reaction history following treatment with Dysport (abobotulinumtoxina) 1 No more than 1 ml should generally be administered at any single injection site 1 Dose Range in Dysport Units 1,9 Torticollis Sternocleidomastoid... Trapezius... Scalenus (anterior) Laterocollis Levator scapulae... Trapezius... Scalenus (medius/anterior) IMPORTANT SAFETY INFORMATION (continued) Use in Pregnancy Based on animal data Dysport may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Dysport should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Dosing: Adult Cervical Dystonia It s Time 19

20 For adults with spasticity or cervical dystonia A simplified dilution approach 1 Diluent* per Dysport 500-Unit Vial Resulting Units per 0.1 ml 1.0 ml 2.0 ml 2.5 ml Dysport 50 Units Dysport 25 Units Dysport 20 Units For other dilution options, refer to Table 1: Dilution Instructions for Dysport Vials (500 Units and 300 Units) in package insert Section 2.1: Instructions for Safe Use 3 points to keep in mind with Dysport 1 1. Vacuum. When reconstituting Dysport, insert the needle into the vial and allow the diluent to be pulled into the vial by partial vacuum. Do not use the vial if no vacuum is observed. 2. Swirl. Swirl Dysport gently in the vial to dissolve, rather than shaking or rolling. 3. Vent. When using more than 2 ml of diluent, vent the vial to release the pressure if entering the vial again to withdraw the diluted Dysport. *Diluent is sterile, Preservative-free 0.9 Sodium Chloride Injection USP. Dysport (abobotulinumtoxina) is given by intramuscular injection. IMPORTANT SAFETY INFORMATION (continued) Pediatric Use Based on animal data Dysport may cause atrophy of injected and adjacent muscles; decreased bone growth, length, and mineral content; delayed sexual maturation; and decreased fertility. Geriatric Use In general, elderly patients should be observed to evaluate their tolerability of Dysport, due to the greater frequency of concomitant disease and other drug therapy. Subjects aged 65 years and over who were treated with Dysport for lower limb spasticity reported a greater percentage of fall and asthenia as compared to those younger (10 versus 6, and 4 versus 2, respectively). 20 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, on the following pages, and the accompanying Full Prescribing Information.

21 A single point of contact for your practice Information and guidance on product support C.L.I.M.B. Hands-on Injection Training Reimbursement Assistance Copay Program for Eligible Patients Dysport Neuroscience Account Specialist Product Acquisition IPSEN CARES Support Programs Continuum of Learning to Improve Management with Botulinum Toxin. See Patient Eligibility & Terms and Conditions on page 23 of this brochure. Dilution/Support It s Time 21

22 For adults with spasticity or cervical dystonia National Dysport coverage overview Broad regional & national coverage for Dysport patients For adult patients with upper limb spasticity or lower limb spasticity, Dysport (abobotulinumtoxina) has national coverage without restrictions* for: 86 Commercial 100 Medicare (Part B) 95 Medicare (Part D) 87 Medicaid For adult patients with cervical dystonia, Dysport has national coverage without restrictions* for: 99 Commercial 100 Medicare (Part B) 99 Medicare (Part D) 96 Medicaid This document represents no promise or guarantee concerning coverage or levels of reimbursement. It is recommended that you contact your local payers with regard to local reimbursement policies and practices. Please consult your counsel or reimbursement specialist on reimbursement or billing questions specific to your practice. Coverage data provided by Zitter Health Insights and current as of July *Limitations/conditions placed by payers that are aligned or broader than Dysport s FDA-approved indications. Medicaid covers both state and managed Medicaid plans. References: 1. Dysport (abobotulinumtoxina) [Prescribing Information]. Basking Ridge, NJ: Ipsen Biopharmaceuticals, Inc; June Simpson DM, Hallett M, Ashman EJ, et al. Neurol Accessed August 30, Editor s Note. Neurol Accessed August 30, Data on file. Ipsen Biopharmaceuticals, Inc. Basking Ridge, NJ. 5. Truong D, Brodsky M, Lew M, et al; Global Dysport Cervical Dystonia Study Group. Parkinsonism Relat Disord. 2010;16: Truong D, Duane DD, Jankovic J, et al. Mov Disord. 5;20: Esquenazi A, Alfaro A, Ayyoub Z, et al. PM R pii: S (16) doi: /j.pmrj [Epub ahead of print]. Accessed August 30, NeuroRehabResource.org Web site. Accessed August 30, Blitzer E, Benson BE, Guss J. Botulinum Neurotoxin for Head and Neck Disorders. New York, NY. Thieme Medical Publishers, Inc IMPORTANT SAFETY INFORMATION (continued) To report SUSPECTED ADVERSE REACTIONS or product complaints, contact Ipsen at You may also report SUSPECTED ADVERSE REACTIONS to the FDA at FDA-1088 or 22 Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information.

23 The Dysport Copay Assistance Program Patient savings on private insurance copay, deductible, and coinsurance costs Savings may be applied for up to four injections per calendar year Savings up to $5,000 per year for treatment costs for eligible patients with the Dysport (abobotulinumtoxina) Copay Assistance Program Eligible patients may receive up to $5,000 throughout the calendar year on their Dysport injections. Program exhausts at the end of the calendar year, 4 injections, or a maximum benefit of $5,000, whichever comes first. Patients must enroll annually to receive a continued benefit. Patient Eligibility & Terms and Conditions In any calendar year commencing January 1, the maximum copay benefit paid by Ipsen Biopharmaceuticals, Inc. will be $5,000, covering no more than four (4) Dysport treatments. For cash-pay patients, the maximum copay benefit amount per eligible Dysport treatment is $1,250, subject to the annual maximum of $5,000 in total. There could be additional financial responsibility depending on the patient s insurance plan. Patients who are eligible to participate (i.e. prescriptions or coverage could be paid in part or in full) in any state or federally funded programs, including, but not limited to, Medicare or Medicaid, VA, DOD, or TRICARE (collectively, Government Programs ) are not eligible for copay assistance through IPSEN CARES. Patients residing in Massachusetts, Minnesota, Michigan, or Rhode Island can only receive assistance with the cost of Ipsen products but not the cost of related medical services (injection). Patients receiving free starter therapy through the IPSEN CARES program are not eligible for the copay assistance program while they are waiting for insurance prescription coverage to begin. Patients receiving assistance through another assistance program or foundation, free trial, or other similar offer or program, also are not eligible for the copay assistance program during current enrollment year. Patient or guardian is responsible for reporting receipt of copay savings benefit to any insurer, health plan, or other third party who pays for or reimburses any part of the prescription filled through the program, as may be required. Additionally, patients may not submit any benefit provided by this program for reimbursement through Flexible Spending Account, Health Savings Account, or Health Reimbursement Account. Ipsen reserves the right to rescind, revoke, or amend these offers without notice at any time. Ipsen and/or TrialCard, Incorporated are not responsible for any transactions processed under this program where Medicaid, Medicare, or Medigap payment in part or full has been applied. Cash-paying patients are eligible to participate. Cash-pay patients are defined for purposes of this program as patients without insurance coverage or who have commercial insurance that does not cover Dysport. Medicare Part D enrollees who are in the prescription drug coverage gap (the donut hole ) are not considered cash-pay patients, and are not eligible for the copay benefit. Data related to your participation may be collected, analyzed, and shared with Ipsen for market research and other purposes related to assessing the program. Data shared with Ipsen will be de-identified, meaning it will not identify you. Void outside of the United States and its territories or where prohibited by law, taxed, or restricted. This program is not health insurance. No other purchase is necessary. Offer expires December 31, It s Time 23 About Dysport Access/ Copay Assistance

24 For adults with spasticity or cervical dystonia How long does your patients symptom * relief last? Consider Dysport because a long duration of response should matter Proven efficacy with Dysport (abobotulinumtoxina) In adult ULS 1 Significantly reduced muscle tone in primary target muscle group vs placebo at Week 4 based on Modified Ashworth Scale (MAS) score (P 0.05) Significantly greater response to treatment vs placebo at Week 4 based on Physician s Global Assessment (PGA) (P 0.05) The most common adverse reactions ( 2 and greater than placebo in either Dysport group) for Dysport 500 Units, Dysport 1,000 Units, and placebo were: nasopharyngitis, urinary tract infection, muscular weakness, musculoskeletal pain, dizziness, fall, and depression In adult LLS 1 Significantly reduced muscle tone at affected ankle joint vs placebo at Week 4 based on MAS score (P<0.05) The most common adverse reactions ( 5) in any Dysport dose group were falls, muscular weakness, and pain in extremity In adult CD 1,4-6 Significantly reduced abnormal head position vs placebo based on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score at Week 4 (P 0.05) Significantly relieved neck pain vs placebo based on Visual Analogue Pain Scale (VAS-Pain) at Week 4 (P 0.05) Most common adverse reactions ( 5 and greater than placebo) for Dysport 500 Units and placebo were: muscular weakness, dysphagia, dry mouth, injection site discomfort, fatigue, headache, musculoskeletal pain, dysphonia, injection site pain, and eye disorders In clinical trials, retreatment was between 12 and 16 weeks or longer 1 * Symptoms of spasticity can include abnormal increase in muscle tone and muscle spasm. IMPORTANT SAFETY INFORMATION (continued) Select Important Safety Information Dysport and all botulinum toxin products have a Boxed Warning which states that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Those symptoms include swallowing and breathing difficulties that can be life-threatening. Please see additional Important Safety Information, including Boxed Warning regarding distant spread of toxin effect, throughout this brochure, and the accompanying Full Prescribing Information. Dysport (abobotulinumtoxina) for injection, for intramuscular use 300- and 500-Unit vials. DYSPORT and C.L.I.M.B. are registered trademarks of Ipsen Biopharm Limited. IPSEN CARES is a registered trademark of Ipsen S.A Ipsen Biopharmaceuticals, Inc. September 2017 Printed in USA DYS-US It s Time