DOCSLIB.ORG

How Does Risdiplam Compare in Infantile-Onset Spinal Muscular Atrophy (SMA)? Preliminary Indirect Treatment Comparisons Based on FIREFISH Part 1 Data

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

How does risdiplam compare in infantile-onset spinal muscular atrophy (SMA)? Preliminary indirect treatment comparisons based on FIREFISH Part 1 data Daigl M,1 Kotzeva A,1 Gorni K,1 Evans R,2 Hawkins N,2 Scott DA,2 Mahajan A,3 Baranello G,4,5 Servais L6,7 1F. Hoffmann-La Roche Ltd, Basel, Switzerland; 2Visible Analytics, Oxford, UK; 3Bridge Medical Consulting Ltd., London, UK; 4The Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, London, UK (current affiliation);5 Carlo Besta Neurological Research Institute Foundation, Developmental Neurology Unit, Milan, Italy; 6Division of Child Neurology, Neuromuscular Reference Center, Department of Pediatrics, University Hospital Liège, Belgium; 7MDUK Oxford Neuromuscular Centre, Oxford, UK. Background Motor milestones analysis • In the last few years, innovative drugs have emerged for SMA and are being evaluated by • MAIC analysis of HINE-2 motor milestone response with risdiplam versus nusinersen gave an regulators, payers, and HTA bodies across the globe. OR of 5.79 (95% CI 0.98–46.19), while risdiplam versus BSC gave an OR of 379.71 (95% CI 75.19–1070.54) (Figure 2). — None of these drugs have been compared in head-to-head trials. • In this analysis, indirect treatment comparison (ITC) evaluated the relative efficacy of risdiplam Figure 2. HINE-2 motor milestone response* against nusinersen (SPINRAZA®) or onasemnogene abeparvovec-xioi (ZOLGENSMA®) in patients with infantile-onset (Type 1) SMA. 100 • FIREFISH (NCT02913482) is an open-label, multicenter clinical study assessing the safety, 80 tolerability, pharmacokinetics, pharmacodynamics and efficacy of risdiplam in infants with infantile-onset SMA.1 60 — Part 1: Dose-finding period followed by open-label extension. 40 — Part 2: Efficacy and safety at the dose selected in Part 1. Responders, % • Individual patient data (IPD) from the 21 patients in the dose-finding Part 1 of the FIREFISH 20 study of risdiplam1 were included in this analysis. 0 Risdiplam Risdiplam Nusinersen BSC (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) unadjusted) matching-adjusted Methods to ENDEAR) • Comparator studies were identified through a systematic literature review of published articles Comparator Unadjusted comparison MAIC and congress abstracts up to February 2018. (STUDY) Weighted number Responders/ OR for risdiplam OR for risdiplam — Eight studies were identified across four compounds in infantile-onset SMA of responders/sum sample size against comparator† against comparator† (see additional material). of weights (% [95% CI]) (95% CI) (95% CI) 1 (% [95% CI]) — Analyses were performed on the FIREFISH Part 1 study of risdiplam (NCT02913482), 2 the ENDEAR study of nusinersen (NCT02193074) and the CL-101 study of onasemnogene Risdiplam 14/21 13.59/15.87 - - abeparvovec (NCT02122952).3 (FIREFISH Part 1) (67 [43–86]) (86 [70–100]) • Matching-adjusted indirect comparison (MAIC) is a population-adjusted method where IPD Nusinersen 37/73 1.95 37/73 5.79 from studies of one treatment are ‘weighted’ so that summary baseline characteristics match (ENDEAR) (51 [39–63]) (0.73–5.84) (51 [39–63]) (0.98–46.19) other studies.4 BSC 0/37 145.00 0/37 379.71 — MAIC aims to adjust for imbalances between trials that may influence outcome. (ENDEAR sham control arm) (0 [0–9]) (57.00–396.43)‡ (0 [0–9]) (75.19–1070.54)‡ 5,6 • Data was extracted from published comparator manuscripts and digitized, before being *Infants were considered to have a motor milestone response if they met the following two criteria: (1) improvement in at least one category (i.e. an increase in the score for head control, rolling, sitting, crawling, standing, or walking of ≥1 point, an increase in the score for kicking of compared to FIREFISH Part 1 IPD. ≥2 points, or achievement of the maximal score for kicking) and (2) more categories with improvement than worsening (i.e. a decrease in the score for head control, rolling, sitting, crawling, standing, or walking of ≥1 point or a decrease in the score for kicking of ≥2 points). HINE-2 motor milestone achievement in infants is assessed at the latest of Days 183, 302 or 394 for patients in ENDEAR (stopped at interim)5 and at 12 months for FIREFISH Part 1. Infants who died or were withdrawn from the trial were considered to have no response regardless of length of follow-up. †OR >1 favors risdiplam over comparator. ‡OR calculated using the half-cell correction. Bootstrap CIs are calculated from N=1000 bootstrap Results samples for FIREFISH. Clopper Pearson CIs are used for ENDEAR. Baseline characteristics • MAIC analysis of sitting without support with risdiplam versus nusinersen gave an OR of 9.22 (95% CI 2.62–29.06), while risdiplam versus BSC gave an OR of 62.66 • SMN2 copy number, duration of symptoms, age at time of first dose, functional score at (95% CI 21.39–154.41) (Figure 3). baseline and ventilatory/nutritional support have been reported to influence outcomes.7–12 • Duration of symptoms, age at first dose and functional score at baseline were selected for the Figure 3. HINE-2 sitting without support (stable sits and pivots) matching based on expert clinicians’ opinion. 100 • All patients had two SMN2 gene copies (Table 1). 80 • Duration of symptoms was not reported in the CL-101 study.3,6 Age at symptom onset was used in the matching adjustment. 60 Table 1. Baseline characteristics before matching 40 Nusinersen and Onasemnogene Risdiplam Responders, % BSC abeparvovec Baseline characteristic (FIREFISH Part 1)1 20 (ENDEAR)2, 5 (CL-101)3,6 N=21 N=121 N=12 0 Risdiplam Risdiplam Nusinersen BSC Mean age at first dose, days 178 169 ~103* (FIREFISH (FIREFISH (ENDEAR) (ENDEAR) (SD [range]) (42 [102–213]) (NR [30–262]) (NR [27–240]) unadjusted) matching-adjusted to ENDEAR) Female gender, % 71 55 58 Comparator Unadjusted comparison MAIC White race, % 81 NR 92 (STUDY) Weighted number Responders/ OR for risdiplam † of responders/sum OR for risdiplam Mean age at symptom onset, weeks 8.1 8.5 ~6.1 sample size against comparator† † of weights against comparator (SD [range]) (3.2 [4–13.1]) (NR [1–20]) (NR [0–13]) (%; 95% CI) (95% CI) (95% CI) (%; 95% CI) Mean disease duration at screening, 104 ~94‡ NR Risdiplam 6/21 7.18/15.87 days (SD [range]) (38 [37–163]) (NR [0–181]) - - (FIREFISH) (29 [10–48]) (45; [18–72]) 14.1 14.3 ~8.6§ Mean age at diagnosis, weeks (SD [range]) Nusinersen 6/73 4.47 6/73 9.22 (5.8 [4–23.3]) (NR [0–30]) (NR [0–19]) (ENDEAR) (8 [3–17]) (1.18-10.15) (8; [3–17]) (2.62–29.06) CHOP-INTEND, mean score 24 27 28 BSC 0/37 31.45 0/37 62.66 (SD [range]) (6 [10–34]) (7.94 [NR]) (NR [12–50]) (ENDEAR sham control arm) (0 [0–9]) (9.62–68.48)‡ (0 [0–9]) (21.39–154.41)‡ Patients with nutritional support: Unable to 5 10 NR HINE-2 motor milestone achievement in infants is assessed at the latest of Days 183, 302 or 394 for patients in ENDEAR (stopped at interim)5 swallow/gastrointestinal tube feeding, % and at Day 365 for FIREFISH Part 1. Infants who died, or were withdrawn from the trial were considered to have no response regardless of length of follow-up. †OR>1 favors risdiplam over comparator; ‡OR calculated using the half-cell correction. Bootstrap CIs are calculated from N=1000 Patients with ventilatory support, % 24 22 17 bootstrap samples for FIREFISH. Clopper Pearson CIs are used for ENDEAR. 1.0 1.4 • ITC of adverse events (AEs) was not performed, however; HINE-2 score, mean (SD [range]) NR (0.7 [0–3]) (1.2 [NR]) — as of February 2019, there have been no drug-related safety findings in FIREFISH Part 1 13 Proportion of patients with two copies leading to withdrawal of any patients 100 100 100 13 of SMN2, % — AEs were reflective of the underlying disease. In ENDEAR, the incidence and severity 5 *3.4 months, †1.4 months, ‡13.2 weeks, §60 days. of AEs were similar in treatment and control groups. Matching factors are in bold. Treatment with risdiplam, nusinersen and onasemnogene abeparvovec are always undertaken in conjunction with BSC. The BSC population in this analysis is taken from the sham control arm of the ENDEAR study.5 MAIC analysis to compare with CL-101 (onasemnogene abeparvovec) • Matching the average characteristics of ENDEAR with FIREFISH Part 1 was successful. • MAIC of FIREFISH Part 1 versus CL-101 aggregate data was not feasible due to lack of overlap The ESS of FIREFISH Part 1 was reduced to 12.8 after matching (see supplementary material). of mean values and ranges. — Matching FIREFISH Part 1 to CL-101 gave an ESS of 1.8 (see supplementary material). MAIC analyses to compare with ENDEAR (nusinersen) • An unadjusted (naïve) comparison would be expected to be biased in favor of onasemnogene Event-free survival* abeparvovec due to: — younger age of patients at time of treatment initiation • MAIC of event-free survival comparing risdiplam (FIREFISH Part 1) with nusinersen (ENDEAR) or BSC (ENDEAR sham control arm) gave HRs of 0.23 (95% CI 0.00–0.66) and 0.11 — differences in disease duration prior to treatment (95% CI 0.00–0.30), respectively (Figure 1; Table 2). — greater CHOP-INTEND total scores at baseline. Figure 1. Kaplan–Meier curves for event-free survival* Risdiplam Risdiplam (FIREFISH (FIREFISH Nusinersen BSC Conclusions unadjusted) matching-adjusted (ENDEAR) (ENDEAR) 1.00 to ENDEAR) • Preliminary results suggest that treatment of infantile-onset SMA with risdiplam may lead to longer event-free survival versus nusinersen, or BSC. • Risdiplam may also yield a better achievement of HINE-2 motor milestones versus nusinersen 0.75 or BSC alone.
Recommended publications
  • Spinraza™ (Nusinersen)

    Spinraza™ (Nusinersen)

    Spinraza™ (nusinersen) (Intrathecal) Document Number: IC-0291 Last Review Date: 08/03/2021 Date of Origin: 01/31/2017 Dates Reviewed: 01/2017, 02/2017, 01/2018, 08/2018, 06/2019, 08/2020, 08/2021 I. Length of Authorization Coverage will be provided annually and may be renewed. II. Dosing Limits A. Quantity Limit (max daily dose) [NDC Unit]: • Loading: 1 vial on D1, D15, D29, and D59 • Maintenance: 1 vial every 112 days B. Max Units (per dose and over time) [HCPCS Unit]: • Loading: 120 billable units on D1, D15, D29, and D59 • Maintenance: 120 billable units every 112 days III. Initial Approval Criteria1-12 • Submission of medical records related to the medical necessity criteria is REQUIRED on all requests for authorizations. Records will be reviewed at the time of submission. Please provide documentation via direct upload through the PA web portal or by fax. Coverage is provided in the following conditions: Spinal Muscular Atrophy (SMA) † Ф • Patient must not have previously received treatment with SMA gene therapy (i.e., onasemnogene abeparvovec-xioi); AND • Patient will not use in combination with other agents for SMA (e.g., onasemnogene abeparvovec, risdiplam, etc.); AND • Patient must not have advanced disease (complete limb paralysis, permanent ventilation support, etc.); AND Moda Health Plan, Inc. Medical Necessity Criteria Page 1/5 Proprietary & Confidential © 2021 Magellan Health, Inc. • Patient must have the following laboratory tests at baseline and prior to each administration*: platelet count, prothrombin time; activated
  • 2017 ANNUAL REPORT | Translating SCIENCE • Transforming LIVES OUR COMMITMENT Make Every Day Count at PTC, Patients Are at the Center of Everything We Do

    2017 ANNUAL REPORT | Translating SCIENCE • Transforming LIVES OUR COMMITMENT Make Every Day Count at PTC, Patients Are at the Center of Everything We Do

    20 YEARS OF COMMITMENT 2017 ANNUAL REPORT | Translating SCIENCE • Transforming LIVES OUR COMMITMENT Make every day count At PTC, patients are at the center of everything we do. We have the opportunity to support patients and families living with rare disorders through their journey. We know that every day matters and we are committed to making a difference. OUR SCIENCE Our scientists are finding new ways to regulate biology to control disease We have several scientific research platforms focused on modulating protein expression within the cell that we believe have the potential to address many rare genetic disorders. OUR PEOPLE Care for each other, our community, and for the needs of our patients At PTC, we are looking at drug discovery and development in a whole new light, bringing new technologies and approaches to developing medicines for patients living with rare disorders and cancer. We strive every day to be better than we were the day before. At PTC Therapeutics, it is our mission to provide access to best-in-class treatments for patients who have an unmet need. We are a science-led, global biopharmaceutical company focused on the discovery, development and commercialization of clinically-differentiated medicines that provide benefits to patients with rare disorders. Founded 20 years ago, PTC Therapeutics has successfully launched two rare disorder products and has a global commercial footprint. This success is the foundation that drives investment in a robust pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. As we celebrate our 20th year of bringing innovative therapies to patients affected by rare disorders, we reflect on our unwavering commitment to our patients, our science and our employees.
  • Spinraza® (Nusinersen)

    Spinraza® (Nusinersen)

    UnitedHealthcare® Commercial Medical Benefit Drug Policy Spinraza® (Nusinersen) Policy Number: 2021D0059I Effective Date: July 1, 2021 Instructions for Use Table of Contents Page Community Plan Policy Coverage Rationale ....................................................................... 1 • Spinraza® (Nusinersen) Documentation Requirements ...................................................... 3 Applicable Codes .......................................................................... 3 Background.................................................................................... 4 Benefit Considerations .................................................................. 5 Clinical Evidence ........................................................................... 5 U.S. Food and Drug Administration ............................................. 8 References ..................................................................................... 9 Policy History/Revision Information ........................................... 10 Instructions for Use ..................................................................... 11 Coverage Rationale See Benefit Considerations Spinraza® (nusinersen) is proven and medically necessary for the treatment of spinal muscular atrophy (SMA) in patients who meet all of the following criteria: 1-4,22,23 Initial Therapy Diagnosis of spinal muscular atrophy by, or in consultation with, a neurologist with expertise in the diagnosis of SMA; and Submission of medical records (e.g., chart notes, laboratory values)
  • DRUGS REQUIRING PRIOR AUTHORIZATION in the MEDICAL BENEFIT Page 1

    DRUGS REQUIRING PRIOR AUTHORIZATION in the MEDICAL BENEFIT Page 1

    Effective Date: 08/01/2021 DRUGS REQUIRING PRIOR AUTHORIZATION IN THE MEDICAL BENEFIT Page 1 Therapeutic Category Drug Class Trade Name Generic Name HCPCS Procedure Code HCPCS Procedure Code Description Anti-infectives Antiretrovirals, HIV CABENUVA cabotegravir-rilpivirine C9077 Injection, cabotegravir and rilpivirine, 2mg/3mg Antithrombotic Agents von Willebrand Factor-Directed Antibody CABLIVI caplacizumab-yhdp C9047 Injection, caplacizumab-yhdp, 1 mg Cardiology Antilipemic EVKEEZA evinacumab-dgnb C9079 Injection, evinacumab-dgnb, 5 mg Cardiology Hemostatic Agent BERINERT c1 esterase J0597 Injection, C1 esterase inhibitor (human), Berinert, 10 units Cardiology Hemostatic Agent CINRYZE c1 esterase J0598 Injection, C1 esterase inhibitor (human), Cinryze, 10 units Cardiology Hemostatic Agent FIRAZYR icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent HAEGARDA c1 esterase J0599 Injection, C1 esterase inhibitor (human), (Haegarda), 10 units Cardiology Hemostatic Agent ICATIBANT (generic) icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent KALBITOR ecallantide J1290 Injection, ecallantide, 1 mg Cardiology Hemostatic Agent RUCONEST c1 esterase J0596 Injection, C1 esterase inhibitor (recombinant), Ruconest, 10 units Injection, lanadelumab-flyo, 1 mg (code may be used for Medicare when drug administered under Cardiology Hemostatic Agent TAKHZYRO lanadelumab-flyo J0593 direct supervision of a physician, not for use when drug is self-administered) Cardiology Pulmonary Arterial Hypertension EPOPROSTENOL (generic)
  • New Brunswick Drug Plans Formulary

    New Brunswick Drug Plans Formulary

    New Brunswick Drug Plans Formulary August 2019 Administered by Medavie Blue Cross on Behalf of the Government of New Brunswick TABLE OF CONTENTS Page Introduction.............................................................................................................................................I New Brunswick Drug Plans....................................................................................................................II Exclusions............................................................................................................................................IV Legend..................................................................................................................................................V Anatomical Therapeutic Chemical (ATC) Classification of Drugs A Alimentary Tract and Metabolism 1 B Blood and Blood Forming Organs 23 C Cardiovascular System 31 D Dermatologicals 81 G Genito Urinary System and Sex Hormones 89 H Systemic Hormonal Preparations excluding Sex Hormones 100 J Antiinfectives for Systemic Use 107 L Antineoplastic and Immunomodulating Agents 129 M Musculo-Skeletal System 147 N Nervous System 156 P Antiparasitic Products, Insecticides and Repellants 223 R Respiratory System 225 S Sensory Organs 234 V Various 240 Appendices I-A Abbreviations of Dosage forms.....................................................................A - 1 I-B Abbreviations of Routes................................................................................A - 4 I-C Abbreviations of Units...................................................................................A
  • Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New

    Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New

    biomolecules Review Circulating Biomarkers in Neuromuscular Disorders: What Is Known, What Is New Andrea Barp 1,* , Amanda Ferrero 1, Silvia Casagrande 1,2 , Roberta Morini 1 and Riccardo Zuccarino 1 1 NeuroMuscular Omnicentre (NeMO) Trento, Villa Rosa Hospital, Via Spolverine 84, 38057 Pergine Valsugana, Italy; [email protected] (A.F.); [email protected] (S.C.); [email protected] (R.M.); [email protected] (R.Z.) 2 Department of Neurosciences, Drug and Child Health, University of Florence, Largo Brambilla 3, 50134 Florence, Italy * Correspondence: [email protected] Abstract: The urgent need for new therapies for some devastating neuromuscular diseases (NMDs), such as Duchenne muscular dystrophy or amyotrophic lateral sclerosis, has led to an intense search for new potential biomarkers. Biomarkers can be classified based on their clinical value into different categories: diagnostic biomarkers confirm the presence of a specific disease, prognostic biomarkers provide information about disease course, and therapeutic biomarkers are designed to predict or measure treatment response. Circulating biomarkers, as opposed to instrumental/invasive ones (e.g., muscle MRI or nerve ultrasound, muscle or nerve biopsy), are generally easier to access and less “time-consuming”. In addition to well-known creatine kinase, other promising molecules seem to be candidate biomarkers to improve the diagnosis, prognosis and prediction of therapeutic response, such as antibodies, neurofilaments, and microRNAs. However, there are some criticalities that can complicate their application: variability during the day, stability, and reliable performance metrics Citation: Barp, A.; Ferrero, A.; (e.g., accuracy, precision and reproducibility) across laboratories. In the present review, we discuss Casagrande, S.; Morini, R.; Zuccarino, the application of biochemical biomarkers (both validated and emerging) in the most common NMDs R.
  • Refreshing the Biologic Pipeline 2020

    Refreshing the Biologic Pipeline 2020

    news feature Credit: Science Lab / Alamy Stock Photo Refreshing the biologic pipeline 2020 In the absence of face-to-face meetings, FDA and industry implemented regulatory workarounds to maintain drug and biologics approvals. These could be here to stay. John Hodgson OVID-19 might have been expected since 1996) — a small miracle in itself “COVID-19 confronted us with the need to severely impair drug approvals (Fig. 1 and Table 1). to better triage sponsors’ questions,” says Cin 2020. In the event, however, To the usual crop of rare disease and Peter Marks, the director of the Center for industry and regulators delivered a small genetic-niche cancer treatments, 2020 Biologics Evaluation and Research (CBER) miracle. They found workarounds and also added a chimeric antigen receptor at the FDA. “That was perhaps the single surrogate methods of engagement. Starting (CAR)-T cell therapy with a cleaner biggest takeaway from the pandemic related in January 2020, when the outbreak veered manufacturing process and the first to product applications.” Marks says that it westward, the number of face-to face approved blockbuster indication for a became very apparent with some COVID- meetings declined rapidly; by March, small-interfering RNA (siRNA) — the 19-related files that resolving a single they were replaced by Webex and Teams. European Medicines Agency’s (EMA) issue can help a sponsor enormously and (Secure Zoom meeting are to be added registration of the RNA interference accelerate the development cycle. Before this year.) And remarkably, by 31 December, (RNAi) therapy Leqvio (inclisiran) for COVID-19, it was conceivable that a small the US Food and Drug Administration cardiovascular disease.
  • Volume 37 Number 10

    Volume 37 Number 10

    VOLUME 37 NUMBER 10 NOVEMBER 2019 Gates Foundation Plots A Fresh Metric From US To EU: Young Biotechs Early Dialogue: Getting The Most For Market Access: Lives Saved Going It Alone Out Of Advice From HTA Agencies PAGE LEFT BLANK INTENTIONALLY invivo.pharmaintelligence.informa.com STRATEGIC INSIGHTS FOR LIFE SCIENCES DECISION-MAKERS CONTENTS ❚ November 2019 MARKET ACCESS Balancing benefit and value against health care sustainability 10 16 22 In US Drug Pricing Debate, Market Access 2020: Gates Foundation Plots A ICER’s Voice Gets Louder Understanding US Payer Fresh Metric For Market Access: MELANIE SENIOR Expectations Lives Saved The Institute for Clinical and Economic WILLIAM LOONEY WILLIAM LOONEY Review's influence on drug pricing, and Big pharma is facing a difficult US In Vivo visits Gates Medical Research policy, is growing. Spotlighting the worst competitive landscape as its traditional Institute CEO Dr. Penny Heaton to review its drug price rises is one recent example. customers realign to build their own first pipeline of drugs and vaccines to Ten years ago, it would have seemed redoubts of size, scale and reach. attack four of the world’s biggest killers: unthinkable that an independent, Consolidation on the payer side is TB, malaria, enteric diseases and other non-profit organization with no statutory changing the dynamics of success in conditions affecting maternal, newborn power could influence the pricing health care. and child health, as well as highlight the behavior of the US pharmaceutical sector. unique business model of this latest Yet that is what ICER has achieved. 36 addition to the Bill & Melinda Gates Foundation and reveal more about the From US To EU: focus and aims of the Boston, US group.
  • The SMA Market: Assessing the Unknowns ❚ MARKET ACCESS: When Disease Dynamics Change the SMA Market: Assessing the Unknowns

    The SMA Market: Assessing the Unknowns ❚ MARKET ACCESS: When Disease Dynamics Change the SMA Market: Assessing the Unknowns

    The SMA Market: Assessing The Unknowns ❚ MARKET ACCESS: When Disease Dynamics Change The SMA Market: Assessing The Unknowns The introductions of Spinraza and Zolgensma in SMA offer new insights into how to address neurodegenerative diseases. But more real-world evidence is needed. BY ALESSIA DEGLINCERTI, FRANK he landmark FDA approval of Novartis AG’s Zolgensma (onasemno- BOROWSKY AND MARK RATNER gene abeparvovec-xioi) in May 2019 shook the biopharma world in several ways including its price ($2.1m per dose) and as important, the very small With the approval of two disease data set on which the FDA primarily based its decision – an ongoing open- modifying agents, some patients label single arm trial of 21 infantile-onset patients with spinal muscular with SMA are becoming healthier Tatrophy (SMA) under two years old. Biogen Inc.’s Spinraza (nusinersen) had already and their medical needs are shifting. been approved in SMA in December 2016. As disease-modifying therapies, these compounds are a rarity in the field of neuro- A new natural course of the disease is muscular diseases of genetic origin. They are also at the core of a fascinating, ongo- emerging, with a larger population of ing real-world case study in how the natural course of a disease can change rapidly. individuals having stabilized disease. How companies’ SMA drug development and market access strategies evolve, both in But the extent of residual issues is not yet known – a picture that will only terms of new disease-modifying agents and supportive therapies that address residual come into focus over time. symptoms, could become a blueprint for other neuromuscular diseases like Duchenne’s Muscular Dystrophy (DMD) or Huntington’s Disease.
  • NHS England Risdiplam EAMS Framework

    NHS England Risdiplam EAMS Framework

    FRAMEWORK OF ADVICE ON THE RISDIPLAM EARLY ACCESS TO MEDICINES SCHEME Background On 17 September 2020, Risdiplam was made available via the Early Access to Medicines Scheme (EAMS), details of which can be found at: https://www.gov.uk/government/publications/risdiplam-in-the-treatment-of-type-1- and-type-2-spinal-muscular-atrophy-sma-in-patients-2-months-of-age-and-older The EAMS scientific opinion issued to Roche Products Limited is for Risdiplam 0.75 mg/ml powder for oral solution in the treatment of type 1 and type 2 Spinal Muscular Atrophy (SMA) in patients 2 months and older who are not suitable for authorised treatments. The questions in the NHS England Blueteq form are attached for reference at Appendix A. The NHS England Nusinersen Clinical Panel, which is also established to offer advice more generally on the treatment and care of patients with spinal muscular atrophy, was asked to develop a framework of advice for clinicians to assist in interpreting the EAMS scientific opinion. The information below is a framework of advice for clinicians to assist in interpreting the EAMS scientific opinion and is not a directive from NHS England. The Clinical Panel understands that each patient case has unique factors and the treating physician must acknowledge that the patient fits the EAMS indication of not suitable for authorised treatments. This is in the context of nusinersen being available to eligible patients through a managed access agreement and onasemnogene abeparvovec being evaluated by NICE. The Clinical Panel is also able to offer advice on individual cases.
  • Rxoutlook® 1St Quarter 2019

    Rxoutlook® 1St Quarter 2019

    ® RxOutlook 1st Quarter 2020 optum.com/optumrx a RxOutlook 1st Quarter 2020 Orphan drugs continue to feature prominently in the drug development pipeline In 1983 the Orphan Drug Act was signed into law. Thirty seven years later, what was initially envisioned as a minor category of drugs has become a major part of the drug development pipeline. The Orphan Drug Act was passed by the United States Congress in 1983 in order to spur drug development for rare conditions with high unmet need. The legislation provided financial incentives to manufacturers if they could demonstrate that the target population for their drug consisted of fewer than 200,000 persons in the United States, or that there was no reasonable expectation that commercial sales would be sufficient to recoup the developmental costs associated with the drug. These “Orphan Drug” approvals have become increasingly common over the last two decades. In 2000, two of the 27 (7%) new drugs approved by the FDA had Orphan Designation, whereas in 2019, 20 of the 48 new drugs (42%) approved by the FDA had Orphan Designation. Since the passage of the Orphan Drug Act, 37 years ago, additional regulations and FDA designations have been implemented in an attempt to further expedite drug development for certain serious and life threatening conditions. Drugs with a Fast Track designation can use Phase 2 clinical trials to support FDA approval. Drugs with Breakthrough Therapy designation can use alternative clinical trial designs instead of the traditional randomized, double-blind, placebo-controlled trial. Additionally, drugs may be approved via the Accelerated Approval pathway using surrogate endpoints in clinical trials rather than clinical outcomes.
  • CP.PHAR.477 Risdiplam (Evrysdi)

    CP.PHAR.477 Risdiplam (Evrysdi)

    Clinical Policy: Risdiplam (Evrysdi) Reference Number: CP.PHAR.477 Effective Date: 08.07.20 Last Review Date: 08.20 Line of Business: Commercial, HIM, Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Risdiplam (Evrysdi™) is a survival motor neuron 2 (SMN2) gene pre-mRNA splicing modifier. FDA Approved Indication(s) Evrysdi is indicated for the treatment of spinal muscular atrophy (SMA) in patients 2 months of age and older. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Evrysdi is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Spinal Muscular Atrophy (must meet all): 1. Diagnosis of SMA with documentation of both of the following (a and b): a. Genetic testing quantifying number of copies of SMN2 gene ≥ 1 but ≤ 4; b. Member is symptomatic; 2. Genetic testing confirms the presence of one of the following (a, b, or c): a. Homozygous deletions of SMN1 gene (e.g., absence of the SMN1 gene); b. Homozygous mutation in the SMN1 gene (e.g., biallelic mutations of exon 7); c. Compound heterozygous mutation in the SMN1 gene [e.g., deletion of SMN1 exon 7 (allele 1) and mutation of SMN1 (allele 2)]; 3. Prescribed by or in consultation with a neurologist; 4. Age ≥ 2 months; 5. Documentation of one of the following baseline scores (see Appendix D) (a or b): a.