NEWS 7
ausdoc . com . au 14 MARCH 2025
NEWS 7
Optimism over new ‘ non-addictive ’ analgesic
Rachel Fieldhouse THE US Food and Drug Administration has approved a new drug for moderate to severe acute pain for the first time in 25 years .
Called suzetrigine , the first-inclass agent is meant to hold the elusive promise of analgesia without risk of addiction .
Professor Ric Day , a clinical pharmacologist at UNSW Sydney , calls it an exciting advance following “ lots of drugs that have come along over the years related to opioids ”.
“ People said they were not going to cause dependence , but we ’ ve been disappointed over and over again ,” he said .
Pregabalin was routinely touted as a non-opioid analgesic with fewer risks , but postmarketing studies have shown the dangers . Another example cited has been gabapentin .
Suzetrigine ’ s maker Vertex Pharmaceuticals said the drug — called VX-548 in early trials — has a “ favourable safety profile without addictive potential ”.
Professor Day said this is “ entirely possible ” because of its very different mechanism to reduce pain .
The drug binds to voltage-gated sodium channel 1.8 ( Na V
1.8 ), stopping pain signals in the peripheral nervous system from travelling to the CNS .
As Na V
1.8 is absent from the brain , suzetrigine will not have the same CNS side effects as non-selective sodium-channel blockers , nor the same addictive potential as opioids , its developers claimed .
However , Professor Day stressed long-term studies are necessary to confirm this .
The drug is taken at a 100mg loading dose , followed by 50mg twice daily for up to 14 days .
The recent approval followed fasttrack and ‘ breakthrough therapy ’ designations and consideration of phase II and phase III trials .
A phase II study published last year in The New England Journal of Medicine involved 303 patients who underwent bunion surgery and 278 abdominoplasty patients , mainly women .
The 100mg / 50mg suzetrigine regimen resulted in greater pain reduction over 48 hours compared with placebo and lower doses of suzetrigine or hydrocodone / paracetamol .
Half as many patients discontinued treatment with ‘ high-dose ’ suzetrigine compared with placebo or hydrocodone / paracetamol .
Phase III trials including expanded cohorts were presented at the 2024 American Society of Anesthesiologists Annual Meeting .
These showed suzetrigine was associated with faster pain relief versus placebo and with or without ibuprofen . However , the new drug was not superior to hydrocodone / paracetamol for reductions in pain intensity scores , and the researchers did not directly compare time to clinically meaningful pain relief between these two treatments .
Professor Day said the most significant difference was suzetrigine ’ s slower
‘ It takes a little while to get to the peak for the parent drug , but then it ’ s broken down to an active metabolite .’
onset compared with the opioid / paracetamol combination .
“ It takes a little while to get to the peak for the parent drug , but then it ’ s broken down to an active metabolite and both of those have got reasonably long half-lives , so that ’ s good ,” he said .
Vertex Pharmaceuticals also investigated addictive potential in animal models and through clinical trial adverse events .
The researchers reported no behavioural effects among animals given high doses that would indicate abuse potential and no signs of dependence after the sudden withdrawal of the drug .
In human trials , fewer patients taking suzetrigine reported any relevant adverse events compared with placebo or hydrocodone / paracetamol .
One patient experienced dissociation , jitteriness or somnolence while taking suzetrigine .
The authors concluded that the lack of Na V
1.8 expression in the CNS — including 190 sampled regions of the brain and spinal cord — was “ fundamental evidence ” against an addiction risk .
Professor Day said the biggest issue for the new agent would probably be interactions .
“ Inducers and inhibitors of [ the
CYP3A4 enzyme ] might affect this drug because it ’ s actually metabolised through that system ,” he explained .
“ And like a lot of drugs , there are issues around risks in pregnancy and breastfeeding that we don ’ t know enough about yet .”
The company also warned that suzetrigine may interfere with the efficacy of hormonal contraceptives containing progestogens other than levonorgestrel or norethindrone .
Professor Day said unanswered questions about abuse risk and side effects could be answered by trials already underway that were evaluating suzetrigine for diabetic peripheral neuropathy and lumbosacral radiculopathy .
In the long term , research could show suzetrigine offered hope for patients with chronic pain as well . “ Chronic pain is really tough , so that ’ s why suzetrigine is interesting ,” Professor Day said .
“ It ’ s not perfect , but it ’ s a step , and if it truly is non-dependence forming , which looks suspiciously like it could be , that ’ s good .”
A spokesperson for the manufacturer told Australian Doctor : “ We are currently focused on commercialising suzetrigine in the US and will continue to evaluate potential opportunities for expansion to other countries in the future .”
N Engl J Med 2023 ; 2 Aug . Pain Ther 2025 ; 8 Jan .
Professor Ric Day .
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* Trimbow is the only triple therapy PBS listed for severe asthma in two strengths and COPD ( 100 / 6 / 10 ) 2
Trimbow 100 / 6 / 10 & 200 / 6 / 10 are indicated for maintenance treatment ; in adults with asthma not adequately controlled with a maintenance combination of medium dose or high dose ICS / LABA respectively , and who experienced ≥1 exacerbation ( s ) in the previous year . Trimbow 100 / 6 / 10 is indicated in adults with moderate to severe COPD who are not adequately treated by ICS / LABA or LABA / LAMA . 1
PBS Information : Authority required ( STREAMLINED ). Severe Asthma . Chronic Obstructive Pulmonary Disease ( 100 / 6 / 10 mcg presentation only ). Criteria Apply . Refer to PBS for full information .
Please review Product Information before prescribing . Product Information is available by scanning the QR code .
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Abbreviations : COPD : chronic obstructive pulmonary disease ; ICS : inhaled corticosteroid ; LABA : long-acting beta 2 agonist ; LAMA : long-acting muscarinic antagonist ; PBS : Pharmaceutical Benefits Scheme ; pMDI : pressurised metered dose inhaler . References : 1 . Trimbow Approved Product Information . 2 . Pharmaceutical Benefits Scheme ( PBS ). www . pbs . gov . au . Chiesi Australia Pty Ltd , Hawthorn East , VIC . 3123 , Australia . Tel : + 61 3 9077 4486 ; Fax : + 61 3 8672 0792 ; Email : medinfo . au @ chiesi . com . Copyright © Chiesi 2025 . All rights reserved . Date of preparation : January 2025 . AU-TRI-2500008 . CHIE00211C .
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