Alexion, AstraZeneca Rare Disease, treatment Koselugo® (selumetinib) has been listed on the Pharmaceutical Benefits Scheme (PBS) from 1 August 2024 as the first medication for children aged 2–18 years with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas (PNs) which cannot be completely removed by surgery and meet specific criteria.1,2
NF1 is a rare, progressive genetic condition affecting one in 3,000 individuals worldwide, most commonly diagnosed in children under the age of 10.3,4 In 30–50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas) and cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bladder or bowel dysfunction.5,6 An estimated 550 Australian children aged 2–18 years are impacted by this condition.7
“Historically, the options to treat plexiform neurofibromas have been limited. Due to the unpredictability of PNs, standard management often involves regular monitoring for disease progression and complications, and pain management. Surgical options are complicated by the vascular and infiltrative nature of these tumours, and resection is rarely complete,” said Clinical Associate Professor Mimi Berman, President, Human Genetics Society of Australasia.
“For some children however, PN tumours can grow large enough to impact nearby tissues and organs, limiting their functioning, and causing debilitating pain and disfigurement. This impacts their quality of life including their mental health, education and social relationships. Combined with the ongoing burden of surgeries, as tumours continue to grow and regrow, the impact of PNs on children and their families is profound. We have urgently needed treatment options that target tumour growth,” concluded A/Prof Berman.
Leanne Dib, CEO, Children’s Tumour Foundation of Australia said: “We are absolutely thrilled to see such important progress being made in Australia to ensure children with NF1 who have inoperable plexiform neurofibromas have access to this government-funded medication. These tumours can be painful, disfiguring and lead to malignancy, but the emotional, social and financial toll can be equally as burdensome. Not just for the child, but the whole family. I would like to extend a heartfelt thanks to our community for sharing their experiences and to the Government for listening and providing hope for a better tomorrow.”
Koselugo is the first and only medicine approved and reimbursed in Australia to treat this rare and potentially devastating condition.1,2 It is a MEK inhibitor that blocks specific enzymes (MEK1 and MEK 2) which are involved in stimulating cells to grow.2 Based on the PBS prescribing criteria, it is estimated ~250 Australian children will be eligible for treatment with Koselugo.8
Nicole Gaupset, General Manager, Alexion AstraZeneca Rare Disease, Australasia, welcomed the listing of Koselugo on the PBS for eligible children: “At Alexion, our mission is to transform the lives of people impacted by rare diseases and we are committed to improving equitable access to innovative medicines. We are delighted to see the Australian Government continuing their investment in the health and wellbeing of Australian families affected by rare diseases with the PBS listing of Koselugo.”
Treatment options should be discussed with a patient’s clinician.
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This medicine is subject to additional monitoring in Australia. This will allow quick identification of new safety information. Patients can help by reporting any side effects you may get. Patients can report side effects to their doctor, or directly at https://www.tga.gov.au/reporting-problems. Healthcare professionals are asked to report any suspected adverse events at https://www.tga.gov.au/reporting-problems.
Side effects can also be reported to Alexion at: https://contactazmedical.astrazeneca.com.
PBS Information: From 1 August 2024: Koselugo® is listed on the PBS General Schedule Authority Required (Written) for the treatment of inoperable plexiform neurofibroma(s) in paediatric patients aged 2–18 years with additional criteria. Refer to PBS Schedule for full authority information. |
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No compensation was provided to Clinical Associate Professor Mimi Berman in relation to this announcement and the opinions expressed are her own. She has been briefed by Alexion on the approved use of this product.
Clinical Associate Professor Berman has received consultancy fees/honorarium for speaking engagements, was an Advisory Board member and has received research funding from Alexion.
Notes
About NF1
NF1 is a debilitating genetic condition that is caused by a spontaneous or inherited mutation in the NF1 gene.9 NF1 is associated with a variety of symptoms, including soft lumps on and under the skin (cutaneous neurofibromas) and skin pigmentation (so-called ‘café au lait’ spots) and, in 30–50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas).5,5 These plexiform neurofibromas (PNs) can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bladder or bowel dysfunction.5,9 PNs begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.5,6,10
About Koselugo
Koselugo (selumetinib) is a type of medicine called a MEK inhibitor, which works by blocking specific enzymes (MEK1 and MEK2) which are known to be involved in the growth of tumour cells.2
In Australia, Koselugo is approved for use in paediatric patients aged 2 years and above with NF1, who have symptomatic plexiform neurofibromas that cannot be completely removed by surgery.2
Koselugo® (selumetinib) Minimum Product Information
THERAPEUTIC INDICATION(S): Treatment of paediatric patients aged ≥ 2 years, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. DOSE: 25 mg/m2 orally twice daily until disease progression or unacceptable toxicity (refer to full PI for details of recommended dosage by Body Surface Area). Administration: Take on an empty stomach. Do not consume food 2 hours prior to dosing and 1 hour after dosing. Swallow whole with water, do not chew, dissolve, or open. Do not administer to patients unable to swallow a whole capsule. For dosage modifications refer to full PI. CONTRAINDICATIONS: Hypersensitivity to selumetinib or to any of the excipients; Severe hepatic impairment. SPECIAL WARNINGS AND PRECAUTIONS FOR USE: Asymptomatic decreases in Left Ventricular Ejection Fraction (LVEF) have been reported in paediatric patients. Evaluate LVEF before treatment initiation to establish baseline values. Prior to initiation, patients should have an LVEF above the institutional LLN; Blurred vision has been reported in paediatric patients receiving selumetinib. Isolated cases of RPED, CSR and RVO have been observed in adult patients. Ophthalmological evaluation prior to treatment initiation and upon reports of new visual disturbances is recommended; Gastrointestinal toxicity including diarrhoea; Skin toxicity, including rashes. Monitor for severe skin rashes; Increased creatine phosphokinase (CPK) occurred in paediatric patients. Obtain serum CPK prior to initiation, periodically during treatment, and as clinically indicated. On increased CPK evaluate patients for rhabdomyolysis or other causes; KOSELUGO can cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 1 week after the last dose; Patients should not take supplemental vitamin E. Laboratory Monitoring/Effects on Laboratory Tests: Refer to Adverse Effects section. Use in Pregnancy-Category D: Ensure adequate contraception in women of childbearing potential, not recommended during pregnancy. A pregnancy test should be performed on women of childbearing potential prior to initiating treatment; Use in Lactation: Breast-feeding mothers are advised not to breast-feed during treatment with KOSELUGO. ADVERSE EFFECTS (UNDESIRABLE EFFECTS): Very common: Vomiting, Abdominal Pain, Diarrhoea, Nausea, Stomatitis, Constipation, Dry mouth, Rash (all), Dry skin, Rash acneiform, Paronychia, Pruritis, Dermatitis, Hair changes, Musculoskeletal pain, Fatigue, Pyrexia, Oedema, Headache, Epistaxis, Haematuria, Proteinuria, Decreased appetite, Decreased injection fraction, Hypertension, Blood pressure increased, Sinus tachycardia, Skin infection, Vision blurred, Facial oedema, Dyspnoea; Laboratory Abnormalities: Increased CPK, Aspartate aminotransferase, Alanine aminotransferase, lipase, potassium, alkaline phosphatase, sodium amylase; Decreased potassium, sodium, haemoglobin, neutrophils, lymphocytes. Others, see full PI. Date Revised: July 2023. KOS/NF1/PI/19JUL2023
For healthcare professionals, please refer to the full Koselugo Product Information before prescribing, which can be accessed at: https://rss.medsinfo.com.au/xi/pi.cfm?product=xipkosel
For more information about Koselugo, the Consumer Medicine Information can be found here: https://rss.medsinfo.com.au/xi/cmi.cfm?product=xickosel
Alexion, AstraZeneca Rare Disease
Alexion, AstraZeneca Rare Disease is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US. Please visit https://alexion.com/worldwide/Australia
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisa tion of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca For more information, please visit www.astrazeneca.com.au
Alexion Pharmaceuticals Australasia Pty Ltd Level 4, 66 Talavera Road, Macquarie Park, NSW 2113. Medical enquiries: 1800 788 189. July 2024. AU/NF1/0001.
Contacts
Nicki Sambuco M: +61 452 446 084 E: nicki@senateshj.com.au
References
1. Australian Government. Department of Health and Aged Care. The Pharmaceutical Benefits Scheme (PBS) [Online]. Available at: https://www.pbs.gov.au/
2. Alexion. 2023 Koselugo® Consumer Medicine Information. [Online] Available at: https://rss.medsinfo.com.au/xi/cmi.cfm?product=xickosel Accessed June 2024
3. Better Health Channel. Neurofibromatosis. [Online] Available at: https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/neurofibromatosis Accessed July 2024
4. National Human Genome Research Institute (US). About Neurofibromatosis. [Online] Available at: https://www.genome.gov/Genetic-Disorders/Neurofibromatosis Accessed July 2024
5. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13:834-43. doi: 10.1016/S1474-4422(14)70063-8
6. NHS. Neurofibromatosis Type 1, Symptoms. Available at https://www.nhs.uk/conditions/neurofibromatosis-type-1/symptoms. Accessed July 2024
7. Alexion Pharmaceuticals Australasia. Data on file, May 2024
8. Alexion Pharmaceuticals Australasia. Data on file, May 2024
9. National Institute of Neurological Disorders and Stroke (US). Neurofibromatosis Fact Sheet. Available at: www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/neurofibromatosis-fact-sheet. Last accessed: July 2024
10. Evans DGR, Ingham SL. Reduced life expectancy seen in hereditary diseases which predispose to early-onset tumors. Appl Clin Genet. 2013;6:53-61