Lupin responds to NICE Appraisal Consultation Document (ACD) on NaMuscla® (mexiletine) to treat symptomatic myotonia in adults with non-dystrophic myotonic disorders (NDM)

Lupin responds to NICE Appraisal Consultation Document (ACD) on NaMuscla® (mexiletine) to treat symptomatic myotonia in adults with non-dystrophic myotonic disorders (NDM)

Slough, UK, 16th February 2021: Lupin is disappointed that the National Institute for Health and Care Excellence (NICE) has published an Appraisal Consultation Document (ACD)¹ recommending not to approve NaMuscla (mexiletine) for routine funding to treat symptomatic myotonia in adults with non-dystrophic myotonic disorders (NDM) in England and Wales.

The ACD document is a preliminary recommendation at this stage and may change after further consultation. Lupin is committed to working with NICE to ensure patients in England and Wales have access to the first and only licensed medication for NDM. The Scottish Medicine’s Consortium approved the funding of Namuscla in December 2020 through its orphan drug PACE process. Lupin believes patients living with symptomatic NDM have the right to licensed treatment choices that improve their lives.

NDM is an ultra-rare genetic neuromuscular disorder, affecting 300-400 patients in England and Wales, in which the sufferer's muscles are slow to relax after movement. These symptoms occur intermittently and unexpectedly, often causing muscle weakness, pain, fatigue and impairment of physical activities.²

The European Commission (EC) approved NaMuscla for the symptomatic treatment of myotonia in adults with non-dystrophic myotonic (NDM) disorders in January 2019. NaMuscla has received orphan drug designation from the European Medicines Agency’s Committee for Orphan Medicinal Products (COMP).³

Ben Ellis, Lupin UK General Manager, said: “We are concerned for NDM patients in England and Wales who are currently stable on NaMuscla. In the event of a negative NICE outcome, these patients may be moved to an unlicensed therapy as an alternative, or have no medication. We will work together with NICE to try and find a resolution to prevent this, with equity of patient access across the whole of the UK being our main priority. NaMuscla is the standard of care for patients with NDM, an ultra-rare disease. We are disappointed that the assessment was not assigned as a Highly Specialised Technology appraisal, which was designed to better suit ultra-rare disease technologies such as NaMuscla.”

Lupin has provided a comprehensive data package to demonstrate the long term safety and efficacy of NaMuscla, and the significantly improved quality of life⁴ for NDM patients. Supporting evidence includes three randomised controlled studies^4-6 and two long term studies.^7,8 Lupin continues to invest in this disease area and has further investment commitments for NaMuscla including, but not limited to, a long-term safety study for adults patients and a trial for paediatric patients.

For further information or media enquiries please contact:

Consilium Strategic Communications
Sukaina Virji / Lizzie Seeley /Kris Lam
Tel: +44 (0)20 3709 5700
Email: lupin@consilium-comms.com

Notes for Editors

About Non-Dystrophic Myotonias (NDM)
Non-dystrophic myotonias (NDM) are a heterogenous group of rare neuromuscular disorders caused by mutations within ion channels in the sarcolemma membrane of skeletal muscles and affects 1 in 100,000 people². Non-dystrophic myotonias exhibit both sodium and chloride channelopathies which result in altered membrane excitability. The major clinical manifestation of the non-dystrophic myotonias is muscle stiffness as a consequence of the myotonia- delayed muscle relaxation after voluntary contraction. Additional common symptoms include pain, weakness and fatigue, and can affect different parts of the body, such as legs, arms or facial muscles, more severely.²

Myotonia in NDM patients has an onset in childhood and persists across their lifetime. Although not life limiting, patients with non-dystrophic myotonia can experience significant lifetime morbidity due to stiffness and pain related to myotonia. Patients may perceive that myotonia increases in severity over time, impacting daily life ⁹ . Myotonia is described by patients in a variety of ways (stiffness, cramps, pain, difficulty releasing a fist, or difficulty swallowing or eating) which can contribute to substantial delays in diagnosis and treatment, leading to decreased patient quality-of-life and often significant disability.¹⁰

About mexiletine
In randomized controlled trials^{, 4-6} mexiletine has been shown to significantly reduce myotonia compared to placebo in adult patients with NDM, reducing skeletal muscle hyperexcitability through its use-dependent, voltage-gated, sodium channel blocking actions which are independent of the cause of channel function. This resulted in an improvement in patient quality-of-life and other functional outcomes. The most commonly reported adverse reactions in patients treated with mexiletine are abdominal pain (12%), vertigo (8%) and insomnia (12%) ⁴., demonstrating mexiletine has a good safety profile .

About Lupin Limited
Lupin is an innovation-led transnational pharmaceutical company headquartered in Mumbai, India. The Company develops and commercializes a wide range of branded and generic formulations, biotechnology products and APIs in over 100 markets in the U.S., India, South Africa and across Asia Pacific (APAC), Latin America (LATAM), Europe and Middle-East regions.

The Company supplies medicines in cardiovascular, anti-diabetic, and respiratory segments and has significant presence in the anti-infective, gastro-intestinal (GI), central nervous system (CNS) and women’s health areas. Lupin is the 3rd largest pharmaceutical company in the U.S. by prescriptions and 5th in India by global revenues. The Company invests 10.3% of its revenues in FY2020 on research and development.
Lupin has fifteen manufacturing sites, seven research centers, more than 20,000 professionals working globally¹¹

1. NICE Appraisal consultation document Mexiletine for treating myotonia in adults with non-dystrophic myotonic disorders Feb 2021

2. Matthews E, Fialho D, Tan SV, Venance SL, Cannon SC, Sternberg D, et al. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain 2010; 133 (Pt 1): 9–22.

3. Orphan maintenance assessment report, Namuscla: https://www.ema.europa.eu/en/documents/orphan-maintenance-report/namuscla-orphan-maintenance-assessment-report-initial-authorisation_en.pdf Last accessed Nov 2020

4. Namuscla summary of product characteristics, https://www.medicines.org.uk/emc/product/9838/smpc#gref Last accessed Nov 2020

5. Statland JM, Bundy BN, Wang Y, et al. Consortium for Clinical Investigation of Neurologic Channelopathies. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012; 308(13):1357–1365. [PubMed: 23032552]

6. Stunnenberg B.C, Raaphorst J, Groenewoud H.M.et al. Effect of mexiletine on muscle stiffness in patients with nondystrophic myotonia evaluated using aggregated N-of-1 trials. JAMA. 2018; 320: 2344-2353

7. Suetterlin KJ, Bugiardini E, Kaski JP, et al. Long-term safety and efficacy of mexiletine for patients with skeletal muscle channelopathies. JAMA Neurol. 2015;72(12):1531-1533.

8. Lupin Limited. Long term follow up data from MYOMEX - EMA response Q13 Annex. LUP-NAM-065. Data on file. 2019

1. Trip J, Drost G, Ginjaar HB, Nieman FH, van der Kooi AJ, de Visser M, et al. Redefining the clinical phenotypes of non-dystrophic myotonic syndromes. J Neurol Neurosurg Psychiatry. 2009;80:647–52. [PubMed] [Google Scholar]

1. Trivedi JR, Bundy B, Statland J, et al; CINCH Consortium. Non-dystrophicmyotonia: prospective study of objective and patient reported outcomes. Brain. 2013;136(pt 7):2189-2200.

2. https://wwww.lupin.com/wp-content/uploads/2020/05/lupin-q4fy20-investor-presentation.pdf LUPIN Limited Investor Report FY2020 (Accessed Online: 3rdJuly 2020)