DOCSLIB.ORG

06/01/2021– Unitedhealthcare Community Plan

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
06/01/2021– Unitedhealthcare Community Plan UnitedHealthcare Community Plan of Kentucky Medical Policy Update Bulletin: June 2021 In This Issue Medical Policy Updates Page Updated • Pharmacogenetic Testing – Effective Jun. 1, 2021 ................................................................................................................................................................................................ 3 Revised • Articular Cartilage Defect Repairs – Effective Jul. 1, 2021 .................................................................................................................................................................................... 3 • Cell-Free Fetal DNA Testing – Effective Jul. 1, 2021 .............................................................................................................................................................................................. 6 • Implanted Electrical Stimulator for Spinal Cord – Effective Jul. 1, 2021 .............................................................................................................................................................. 8 • Lower Extremity Invasive Diagnostic and Endovascular Procedures – Effective Jul. 1, 2021 ............................................................................................................................ 9 Replaced/Retired • Femoroacetabular Impingement Syndrome – Effective Jun. 1, 2021 ................................................................................................................................................................. 11 • Otoacoustic Emissions Testing – Effective Jun. 1, 2021 ..................................................................................................................................................................................... 11 Medical Benefit Drug Policy Updates New • Long-Acting Injectable Antiretroviral Agents for HIV – Effective Jul. 1, 2021 ..................................................................................................................................................... 12 • Oxlumo™ (Lumasiran) – Effective Jul. 1, 2021 ...................................................................................................................................................................................................... 13 Revised • Antiemetics for Oncology – Effective Jul. 1, 2021 ................................................................................................................................................................................................ 14 • Benlysta® (Belimumab) – Effective Jul. 1, 2021 .................................................................................................................................................................................................... 21 • Complement Inhibitors (Soliris® & Ultomiris®) – Effective Jul. 1, 2021 ................................................................................................................................................................ 24 • Gonadotropin Releasing Hormone Analogs – Effective Jul. 1, 2021 .................................................................................................................................................................. 30 • Infliximab (Remicade®) – Effective Jul. 1, 2021 .................................................................................................................................................................................................... 32 • Intravenous Bisphosphonates/ Bone Resorption Inhibitors (Zoledronic Acid & Pamidronate Disodium) – Effective Jul. 1, 2021 ............................................................... 33 • Rituximab (Riabni™, Rituxan®, Ruxience®, & Truxima®) – Effective Jul. 1, 2021 .................................................................................................................................................. 35 Page 1 of 65 UnitedHealthcare Community Plan of Kentucky Medical Policy Update Bulletin: June 2021 In This Issue • Spinraza® (Nusinersen) – Effective Jul. 1, 2021 .................................................................................................................................................................................................... 41 • White Blood Cell Colony Stimulating Factors – Effective Jul. 1, 2021 ................................................................................................................................................................ 45 • Xiaflex® (Collagenase, Clostridium, Histolyticum) – Effective Jul. 1, 2021 .......................................................................................................................................................... 48 • Xolair® (Omalizumab) – Effective Jul. 1, 2021 ....................................................................................................................................................................................................... 50 • Zolgensma® (Onasemnogene Abeparvovec-Xioi) – Effective Jul. 1, 2021 .......................................................................................................................................................... 56 Coverage Determination Guideline Updates Updated • Breast Reconstruction Post Mastectomy and Poland Syndrome – Effective Jun. 1, 2021 ............................................................................................................................... 60 • Rhinoplasty and Other Nasal Surgeries – Effective Jun. 1, 2021 ........................................................................................................................................................................ 60 Revised • Ambulance Services – Effective Jul. 1, 2021 ........................................................................................................................................................................................................ 60 • Chiropractic Services – Effective Jul. 1, 2021 ...................................................................................................................................................................................................... 64 Page 2 of 65 UnitedHealthcare Community Plan of Kentucky Medical Policy Update Bulletin: June 2021 Medical Policy Updates Updated Policy Title Effective Date Summary of Changes Pharmacogenetic Jun. 1, 2021 Coverage Rationale Testing Updated list of examples of unproven and not medically necessary pharmacogenetic Multi-Gene Panels for genetic polymorphisms; removed “NeurolDgenetix” Revised Policy Title Effective Date Summary of Changes Coverage Rationale Articular Cartilage Jul. 1, 2021 Coverage Rationale Autologous chondrocyte transplantation (ACT) is proven and medically Defect Repairs Revised language to indicate: necessary for treating individuals with a symptomatic full-thickness articular cartilage defect. o Autologous chondrocyte transplantation (ACT) is proven and medically necessary for ACT is unproven and not medically necessary for treating individuals with the treating individuals with a following indications due to insufficient evidence of efficacy: symptomatic full-thickness Treatment of joints other than the knee articular cartilage defect Growth plates have not closed History of partial-thickness defects o ACT is unproven and not medically necessary for Osteochondritis dissecans (OCD) treating individuals with the Malignancy in the bone, cartilage, fat or muscle of the treated limb following indications due to Active infection in the affected knee Instability of the knee insufficient evidence of efficacy: History of total meniscectomy . Treatment of joints other Repeat ACT than the knee Active inflammatory degenerative, rheumatoid or osteoarthritis . Growth plates have not As initial or first line of surgical therapy closed . History of partial-thickness Microfracture repair to treat full and partial thickness chondral defects of the defects knee is proven and medically necessary. Osteochondritis dissecans (OCD) For medical necessity clinical coverage criteria for ACT and microfracture repair, . Malignancy in the bone, refer to the InterQual® Client Defined 2020, CP: Procedures, Articular Cartilage cartilage, fat or muscle of Defect Repairs (Custom) - UHG. the treated limb ® . Active infection in the Click here to view the InterQual criteria. affected knee . Instability of the knee Osteochondral Autograft and Allograft transplantation is proven and Page 3 of 65 UnitedHealthcare Community Plan of Kentucky Medical Policy Update Bulletin: June 2021 Medical Policy Updates Revised Policy Title Effective Date Summary of Changes Coverage Rationale Articular Cartilage Jul. 1, 2021 . History of total medically necessary for treating individuals with cartilage defects of the Defect Repairs meniscectomy knee. (continued) . Repeat ACT . Active inflammatory For medical necessity clinical coverage criteria for Osteochondral Autograft and degenerative, rheumatoid Allograft transplantation, refer to the InterQual® 2020, Apr. 2020 Release, CP: or osteoarthritis Procedures: . As initial or first line of • Arthroscopy or Arthroscopically Assisted Surgery, Knee surgical therapy • Arthroscopy or Arthroscopically Assisted Surgery, Knee (Pediatric) o Microfracture repair is proven • Arthrotomy, Knee and medically necessary to treat full and partial thickness Click here to view the InterQual® criteria. chondral defects of the knee o
Load more

Recommended publications
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Innovationsreport 2020 Kurzfassung
    Innovationsreport 2020 Auswertungsergebnisse von Routinedaten der Techniker Krankenkasse aus den Jahren 2017 bis 2018 Herausgeber: Gerd Glaeske Erstellt mit freundlicher Unterstützung der Techniker Krankenkasse (TK) 3 Herausgeber Prof. Dr. Gerd Glaeske Experten für ausgewählte Kapitel Prof. Dr. med. Janbernd Kirschner, Bonn Prof. Dr. med. Dieter Ukena, Bremen Prof. Dr. med. Barbara Schmalfeldt, Hamburg Prof. Dr. med. Wolfgang Schramm, München Autoren Prof. Dr. med. Karl Broich, Dr. Stanislava Dicheva‐Radev, Dörte Fuchs, Prof. Dr. Gerd Glaeske, Dr. Marion Haberkamp, Dr. Iris Hinneburg, Friederike Höfel, Prof. Dr. Janbernd Kirschner, Dr. Wiebke Löbker, Anja Lübs, Dr. André S. Morawetz, Lutz Muth, Dr. Frauke Naumann‐Winter, Linda Richter, Saskia Ritter, Dr. Kristin Sauer, Dr. Birgit Schindler unter Mitarbeit von Esra Aksoy, Friederike Höfel, Berit Marquardt, Linda Richter, Marle Wilhelm Anschrift: Universität Bremen, SOCIUM, Mary‐Somerville‐Str. 5, 28359 Bremen Aus Gründen der besseren Lesbarkeit wurde auf die Nennung beider geschlechtsspezifischer Formen verzichtet. Im Allgemeinen ist aber das jeweils andere Geschlecht ebenfalls gemeint. 2 Glossar .......................................................................................... 7 Vorwort zum Innovationsreport 2020 ...........................................15 Vorwort des Herausgebers ............................................................17 1 Einleitung ................................................................................19 2 Ziele und Methodik..................................................................33
    [Show full text]
  • Roche and Novartis Confirm Dual Threat to Biogen's Biggest Growth Driver
    October 04, 2018 Roche and Novartis confirm dual threat to Biogen’s biggest growth driver Amy Brown The sellside’s protestations aside, results at the World Muscle meeting position risdiplam and AVXS-101 as serious challengers to Spinraza in spinal muscular atrophy. Data at the World Muscle Society meeting this week were always going to make for uncomfortable reading for Biogen and Ionis. Competitors are advancing with potentially more effective and more convenient projects than the groups’ antisense spinal muscular atrophy therapy Spinraza, Biogen’s most important sales growth driver. A gene therapy from Novartis is yielding stellar efficacy and survival data in this childhood disease, for instance. However, gene therapies pose their own questions over convenience and affordability, meaning that perhaps the biggest threat to Biogen comes from Roche/PTC Therapeutics’ risdiplam (RG7916). World Muscle data have confirmed that risdiplam is a very viable asset. This oral SMN2 splicing modifier seems to induce stronger responses than Spinraza in patients with SMA type 1, the most severe form of the condition. Sitting unassisted Roche’s SMA type 1 trial is called Firefish, and the group said yesterday that three of 14 enrolled infants had been able to sit unassisted at eight months post treatment. Though the data are very encouraging it is not entirely clear whether this finding substantially improved on an earlier look at the results. Back in June, three of 21 subjects were said to have achieved the same milestone at six months. This metric will ultimately form the primary endpoint of the study, measured from the trial’s 40-patient, pivotal second stage.
    [Show full text]
  • Pharmacotherapy of Spinal Muscular Atrophy (SMA), 5.01.574
    PHARMACY / MEDICAL POLICY – 5.01.574 Pharmacotherapy of Spinal Muscular Atrophy (SMA) Effective Date: Nov. 1, 2020 RELATED MEDICAL POLICIES: Last Revised: Jan. 31, 2021 None Replaces: N/A Select a hyperlink below to be directed to that section. POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY ∞ Clicking this icon returns you to the hyperlinks menu above. Introduction Spinal muscular atrophy (SMA) is a rare disease that leads to muscle weakness and atrophy. SMA affects the muscles of the limbs and trunk. SMA is caused by changes to the survival motor neuron 1 gene (SMN1). This gene creates a protein called the survival motor neuron (SMN) protein. Too little of the SMN protein leads to muscle weakness that gets worse over time and muscles that waste away (atrophy). There are different types of SMA. Type 1 SMA, also known as Werdnig-Hoffman disease or infantile SMA, is the most severe form. Symptoms usually start before 6 months of age. The chance of survival to one year of age is 50 percent. Less severe forms are Type 2, also known as Dubowitz disease, and Type 3, or Kugelberg-Welander disease. Evrysdi™ (risdiplam), Spinraza® (nusinersen), and Zolgensma® (onasemnogene abeparvovec- xioi) are three treatments the Food and Drug Administration has approved for SMA. This policy discusses when the use of Evrysdi™, Spinraza®, and Zolgensma® may be considered medically necessary. Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals.
    [Show full text]
  • Risdiplam Improves Motor Function in Infants with Spinal Muscular Atrophy 20 August 2021, by Alice Mccarthy
    Risdiplam improves motor function in infants with spinal muscular atrophy 20 August 2021, by Alice McCarthy control subjects, the treated infants had improvements in motor function, including the ability to sit unassisted for a period of time. They were more likely than the controls to achieve motor milestones and lived longer than would be expected. Addressing SMA's root cause Boston Children's neurologist Randolph Byers, MD, and neuropathologist Betty Banker, MD, first defined infantile SMA in 1961. Over the past decade, Boston Children's has been heavily involved in the development and clinical testing of Research on SMA goes back more than 50 years. therapies targeting SMA's root cause: an inability to Credit: Children's Hospital Boston make enough of the SMN protein needed for normal motor neuron function. The shortfall is a result of mutations in both SMN1 and its "back-up" gene, SMN2. Until recently, babies and children with spinal muscular atrophy (SMA) lacked any type of In 2004, Darras co-founded the Pediatric treatment capable of stopping the neuromuscular Neuromuscular Clinical Research Network disease from progressing. In SMA, damaged motor (PNCRN) for SMA, a consortium of research neurons in the spinal cord fail to correctly send centers including Boston Children's, to accelerate messages to the muscle cells. As a result, infants the search for treatments. and children with SMA may not be able to hold their head up, sit, or walk, depending on the "One site alone cannot do clinical trials for a rare severity of their mutation. disease," say Darras, who directs the Neuromuscular Center and Spinal Muscular In the New England Journal of Medicine last week, Atrophy Program at Boston Children's.
    [Show full text]
  • Aetna PA Info
    Procedures, programs and drugs that require precertification Participating provider precertification list Starting June 1, 2021 Applies to the following plans (also see General information section #1-#4, #9-#10): Aetna® plans, except Traditional Choice® plans All health benefits and insurance plans offered and/or underwritten by Innovation Health plans, Inc., and Innovation Health Insurance Company, except indemnity plans, Foreign Service Benefit Plan, MHBP and Rural Carrier Benefit Plan All health benefits and health insurance plans offered, underwritten and/or administered by the following: Banner Health and Aetna Health Insurance Company and/or Banner Health and Aetna Health Plan Inc. (Banner|Aetna), Texas Health +Aetna Health Insurance Company and/or Texas Health+Aetna Health Plan Inc. (Texas Health Aetna), Allina Health and Aetna Health Insurance Company (Allina Health| Aetna), Sutter Health and Aetna Administrative Services LLC (Sutter Health | Aetna) Aetna.com 23.03.882.1 R (6/21) For more information, read all general precertification guidelines Providers may submit most precertification requests electronically through the secure provider website or using your Electronic Medical Record (EMR) system portal. (See #1 in the General Information section for more information on precertification.) Services that require precertification: 1. Inpatient confinements (except hospice) 18. Nonparticipating freestanding ambulatory For example, surgical and nonsurgical stays, surgical facility services, when referred by stays in a skilled nursing facility or rehabilitation a participating provider facility, and maternity and newborn stays that 19. Orthognathic surgery procedures, bone exceed the standard length of stay (LOS). (See grafts, osteotomies and surgical #6 in the General Information section.) management of the temporomandibular 2. Ambulance joint Precertification required for transportation by 20.
    [Show full text]
  • News & Analysis
    NEWS & ANALYSIS NEWS IN BRIEF Industry’s interest in RNA- targeted FDA approves first BCMA- targeted therapeutic small- molecule drugs is growing. In April, The FDA has approved GlaxoSmithKline on the drug’s label notes the associated risk Roche partnered with Arrakis Therapeutics (GSK)’s belantamab mafodotin for of severe vision loss. on RNA- targeted small-molecule drug relapsed or refractory multiple myeloma. GSK is still developing the ADC for earlier discovery. Other biotechs that are working The antibody–drug conjugate (ADC) is lines of therapy, and in combination with preclinically on RNA-targeted small molecules the first therapeutic from the crowded other agents. A benefit of the ADC approach include Expansion Therapeutics, Skyhawk BCMA- targeted pipeline to secure approval. is that it provides an off-the- shelf product. Therapeutics and Ribometrix. BCMA, a member of the TNF-receptor BCMA- targeted CAR- T therapies that Asher Mullard superfamily, is expressed on normal B are made to order for each patient are also lymphocytes as well as on multiple myeloma approaching the market, setting the stage FDA approves first GPCR cells. Despite early efforts to target BCMA for a modality showdown. Bristol Myers with canonical monoclonal antibodies, early Squibb and Bluebird Bio resubmitted their biased agonist candidates did not have sufficient efficacy idecabtagene vicleucel for FDA approval The FDA has approved Trevena’s μ- opioid to move forward. In recent years, however, in July, following an earlier submission agonist oliceridine for moderate to severe drug developers have had more success with and refuse- to- file letter. Johnson & Johnson acute pain in adults.
    [Show full text]
  • Spinal Muscular Atrophy As Example
    Risdiplam: Editing on the RNA level – a dream or a nightmare? – Spinal Muscular Atrophy as example Lutz Müller, PhD Distinguished Scientist, Project Leader Roche Pharmaceutical Research and Early Development Roche Innovation Center Basel Spinal Muscular Atrophy (SMA) A terminal disease with huge unmet medical need Type 1 Type 2 Type 3 2 A three party collaboration A joint effort between three parties to develop a life changing treatment for children with SMA with urgency! 3 A protein called SMN, “Survival of Motor Neuron” Spinal motor neurons are dependent on SMN protein • Reduced level of SMN protein is responsible of SMA disease • Essential in all species • Adequate SMN levels are critical for normal development and functioning • Reduced SMN levels result in loss of motor neurons in the spinal cord & progressive muscle atrophy SMA patients type 1 4 SMA disease mechanism: Every species has the SMN1 gene but the SMN2 “rescue” gene is human-specific Healthy subjects >95% 10-30% 70-90% Fully functional Fully functional 5 SMA disease mechanism SMA patients >95% 10-30% 70-90% Fully functional Fully functional SMA patients have in average 2-4 copies of SMN2 gene, this influences SMN protein levels and disease severity 6 SMA disease mechanism Hypothesis >95% Up10-30%10-30% to 95% 70-90%70-90% Drug Fully functional FullyFully functional functional 7 SMN2 gene copy: it is human specific, there is no animal correlate!! Is what we see in animals translatable? In terms of alternative splicing, probably yes, as this is highly conserved! Animal findings: on MoA (splice modification) but off-target è Justification of animal species and safety monitoring in patients based on secondary (off) splice targets è Comparison of affected splice sites (with exon inclusion) across the genome è Comparison of animal cells with patients cells to guide translatability understanding 8 Modifiers of SMN2 splicing as investigated by Roche Science: August 2014, Vol.
    [Show full text]