qanastek/EMEA-V3 huggingface dataset:
Myozyme is designed to replace the human enzyme alpha-glucosidase, which is missing in people with Pompe disease.
Myozyme huwa ddisinjat biex jissostitwixxi l- enzima umana alfa- glukosidażi, li hija nieqsa fil- persuni li jbatu mill- marda ta ’ Pompe.
7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
Is- sustanza attiva f’ Myozyme, 7 Westferry Circus, Canary Wharf, London E14 4HB, UK Tel.
Reproduction is authorised provided the source is acknowledged.
Reproduction is authorised provided the source is acknowledged. alglukosidażi alfa, hija kopja tal- enzima umana magħmula b’ metodu magħruf bħala ‘ teknoloġija tad - DNA rikombinanti ’: l- enzima tiġi prodotta minn ċellola li tkun irċeviet ġene (DNA) li jagħmilha kapaċi tipproduċi l- enzima.
How has Myozyme been studied?
Kif ġie studjat Myozyme?
Myozyme has been studied in two main studies involving a total of 39 babies and infants with Pompe disease.
Myozyme kien studjat f’ żewġ studji ewlenin li involvew total ta ’ 39 tarbija u tifel u tifla żgħar li jabtu mill- marda ta ’ Pompe.
These patients were compared with a ‘ historical comparison group ’ of patients with Pompe disease who had not received treatment and did not take part in the studies.
Dawn il- pazjenti tqabblu ma ’ ‘ grupp ta ’ tqabbil storiku ’ ta ’ pazjenti bil- marda ta ’ Pompe li ma kinux sottoposti għal trattament u ma ħadux sehem fl- istudji.
The main measures of effectiveness were the number of patients who survived and the number who did not need a ventilator.
Il- kejl ewlieni tal - effikaċja kien iż- żmien li għadda bejn it- trattament u l- mewt kif ukoll in- numru ta ’ pazjenti li ma kellhomx bżonn ta ’ ventilatur.
Additional studies looked at the effect of Myozyme in 15 patients with late-onset disease.
Studji addizzjonali eżaminaw l- effett ta ’ Myozyme fi 15- il pazjent li jbatu mill- marda li ħarġet tard.
What benefit has Myozyme shown during the studies?
Liema benefiċċju wera Myozyme waqt l- istudji mwettqa?
In the first main study, which involved babies less than six months old, all 18 patients treated with Myozyme were alive at 18 months of age, and 15 of these did not need ventilation.
Fl- ewwel studju ewlieni, li involva trabi ta ’ età inqas minn sitt xhur, it- 18- il pazjent kollha ttrattati b’ Myozyme kienu ħajjin fl- età ta ’ 18- il xahar, u 15 minn dawn ma ħtiġux ventilatur.
In contrast, only one of the 42 patients in the historical comparison group was alive at 18 months of age.
F’ kuntrast għal dan, wieħed biss mit- 42 pazjent fil- grupp ta ’ tqabbil storiku baqa ’ ħaj fl- età ta ’ 18- il xahar.
The results were confirmed in the other study, which involved children aged between six months and three and a half years.
Ir- riżultati kienu kkonfermati fl- istudju l- ieħor, li involva tfal ta ’ etajiet bejn sitt xhur u tliet snin u nofs.
In late-onset disease, the effect of Myozyme was variable and more difficult to measure.
Fil- marda li tibda tard, l- effett ta ’ Myozyme kien varjabbli u iktar diffiċli biex jitkejjel.
The studies could not prove a clear benefit in this type of the disease.
L- istudji ma setgħux jagħtu prova ta ’ benefiċċju ċar f’ din it- tip ta ’ marda.
What is the risk associated with Myozyme?
X’ inhu r- riskju assoċjat ma ’ Myozyme?
During the studies, the most common side effects with Myozyme (seen in more than 1 patient in 10) were tachycardia (rapid heart rate), flushing (redness), cough, tachypnoea (rapid breathing rate), vomiting, urticaria (hives), rash, pyrexia (fever) and decreased oxygen saturation (low oxygen levels in the blood).
Waqt l- istudji, l- iktar effetti sekondarji komuni b’ Myozyme (li dehru f' iktar minn pazjent 1 minn 10) kienu takikardija (taħbit tal- qalb rapidu), fwawar (vampi), sogħla, takipnea (rata tat- teħid tan- nifs rapida), remettar, urtikarja (ħorriqija), raxx, piressija (deni) u tnaqqis tas- saturazzjoni tal- ossiġenu (livelli baxxi ta ’ ossiġenu fid- demm).
Almost all of these occurred during or just after the infusion.
Kważi dawn kollha seħħew waqt l- infużjoni jew kważi wara.
For the full list of all side effects reported with Myozyme, see the Package Leaflet.
Għal- lista sħiħa ta ’ effetti sekondarji kollha rrappurtati b’ Myozyme, ara l- Fuljett ta ’ Tagħrif.
Patients who receive Myozyme may develop antibodies (proteins that are produced in response to Myozyme).
Il- pazjenti li jirċievu Myozyme jistgħu jiżviluppaw antikorpi (proteini li jiġu prodotti b’ rispons għal Myozyme).
The effect of these antibodies on the safety and effectiveness of Myozyme is not yet clear.
L- effett ta ’ dawn l- antikorpi fuq is- sigurtà u l- effikaċja ta ’ Myozyme għadu mhuwiex ċar.
Myozyme should not be used in people who may be hypersensitive (allergic) to alglucosidase alfa or any of the other ingredients.
Myozyme m’ għandux jintuża f’ persuni li jistgħu jkunu ipersensittivi (allerġiċi) għal alglukosidażi alfa jew għal xi sustanza oħra tiegħu.
Why has Myozyme been approved?
Għaliex ġie approvat Myozyme?
The Committee for Medicinal Products for Human Use (CHMP) decided that Myozyme’ s benefits are greater than its risks for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Pompe disease (acid alpha-glucosidase deficiency).
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li l- benefiċċji ta ’ Myozyme huma ogħla mir- riskji tiegħu għal terapija enzimatika sostituttiva fit- tul f’ pazjenti b’ dijanjożi kkonfermata tal- marda ta ’ Pompe (defiċjenza tal- aċidu alfa- glukosidażi).
The Committee recommended that Myozyme be given marketing authorisation.
Il- Kumitat irrakkomanda li Myozyme jingħata awtorizzazzjoni għat- tqegħid fis- suq.
What information is still awaited for Myozyme?
Liema informazzjoni għadha mistennija għal Myozyme?
The company will continue to study the effect of Myozyme in late-onset patients.
Il- kumpanija se tkompli tistudja l- effett ta ’ Myozyme f’ pazjenti b’ bidu tard tal- marda.
Which measures are being taken to ensure the safe use of Myozyme?
Liema miżuri qed jittieħdu sabiex jiġi assigurat użu sigur għal Myozyme?
The company that makes Myozyme is putting a plan in place to ensure that Myozyme is used safely, mainly by monitoring how patients who receive Myozyme develop antibodies, by setting up a register for all Pompe disease sufferers, and by ensuring that doctors know about the reactions that patients may have to the infusion.
Il- kumpanija li tipproduċi Myozyme qed tpoġġi fis- seħħ pjan biex tassigura li Myozyme jintuża b’ mod sigur, prinċiplament billi tissorvelja kif pazjenti li jirċievu Myozyme jiżviluppaw antikorpi, billi toħloq reġistru għal dawk kollha li jsofru mill- marda ta ’ Pompe, u billi tassigura li t- tobba jkunu jafu dwar ir- reazzjonijiet li l- pazjenti jista ’ jkollhom għall- infużjoni.
Other information about Myozyme:
Aktar tagħrif dwar Myozyme:
The European Commission granted a marketing authorisation valid throughout the European Union for Myozyme to Genzyme Europe B. V. on 29 March 2006.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fuq is- suq fl- Unjoni Ewropea kollha għal Myozyme lil Genzyme Europe B. V. fid- 29 ta ’ Marzu 2006.
The record of Myozyme’ s designation as an orphan medicine can be found here.
Ir- reġistrazzjoni tal- kwalifika ta ’ Myozyme bħala mediċina orfni tista ’ tiġi kkonsultata hawn.
The full EPAR for Myozyme can be found here.
L- EPAR sħiħ għal Myozyme jista ’ jiġi kkonsultat hawn.
EU/ 1/ 06/ 333/ 001
Numru ta ’ l- EU EU/ 1/ 06/ 333/ 001 EU/ 1/ 06/ 333/ 002 EU/ 1/ 06/ 333/ 003
Myozyme
Isem inventat Myozyme Myozyme Myozyme
50 mg
Qawwa 50 mg 50 mg 50 mg
Powder for concentrate for solution for infusion
Għamla farmaċewtika trab għal konċentrat għal soluzzjoni għall- infużjoni trab għal konċentrat għal soluzzjoni għall- infużjoni trab għal konċentrat għal soluzzjoni għall- infużjoni
Intravenous use
Mnejn jingħata Il- pakkett Minn ġol- vina.
Vial (glass)
Kunjett (ħġieġ) Minn ġol- vina.
20 ml
Kontenut 20 ml 20 ml 20 ml
25 vials
Daqs tal- pakkett 1 kunjett 10 kunjett 25 kunjett
Myozyme 50 mg, powder for concentrate for solution for infusion.
Myozyme 50 mg, trab għal konċentrat għal soluzzjoni għall- infużjoni.
One vial contains 50 mg of alglucosidase alfa.
Kunjett wieħed fih 50 mg ta ’ alglucosidase alfa.
After reconstitution, the solution contains 5 mg of alglucosidase alfa/ ml and after dilution, the concentration varies from 0.5 mg to 4 mg/ ml.
Wara r- rikostituzzjoni, is- soluzzjoni jkun fiha 5 mg ta ’ alglucosidase alfa/ ml u wara d- dilwizzjoni, il - konċentrazzjoni tvarja minn 0. 5 mg sa 4 mg/ ml.
White to off-white powder.
Trab ta ’ lewn abjad jew abjad jagħti fil- griż.
Myozyme is indicated for long-term enzyme replacement therapy (ERT) in patients with a confirmed diagnosis of Pompe disease (acid α -glucosidase deficiency).
Myozyme hu indikat għat- terapija tas- sostituzzjoni fit- tul ta ’ l- enzimi (ERT) f’ pazjenti b’ dijanjosi kkonfermata tal- marda ta ’ Pompe (defiċjenza ta ’ acid α- glucosidase).
The benefits of Myozyme in patients with late-onset Pompe disease have not been established (see section 5.1).
Il- benefiċċji ta ’ Myozyme f’ pazjenti bil- marda ta ’ Pompe li sseħħ iktar tard ma kinux stabbiliti (ara sezzjoni 5. 1).
Myozyme treatment should be supervised by a physician experienced in the management of patients with Pompe disease or other inherited metabolic or neuromuscular diseases.
Il- kura b’ Myozyme għandha tkun issorveljata minn tabib b’ esperjenza fl- immaniġġjar ta ’ pazjenti bil - marda ta ’ Pompe jew b’ mard ieħor metaboliku jew newromuskolari li jintiret.
The recommended dosage regimen of alglucosidase alfa is 20 mg/ kg of body weight administered once every 2 weeks as an intravenous infusion.
Il- kors tad- dożaġġ rakkomandat ta ’ alglucosidase alfa hu ta ’ 20 mg/ kg ta ’ piż tal- ġisem, mogħti darba kull ġimagħtejn bħala infużjoni ġol- vini.
Infusions should be administered incrementally.
L- infużjonijiet għandhom jingħataw b’ mod inkrementali.
It is recommended that the infusion begin at an initial rate of 1 mg/ kg/ hr and be gradually increased by 2 mg/ kg/ hr every 30 minutes if there are no signs of infusion associated reactions (IARs) until a maximum rate of 7 mg/ kg/ hr is reached.
Hu rakkomandat li l- infużjoni tinbeda b’ rata inizjali ta ’ 1 mg/ kg/ siegħa u tiżdied gradwalment b’ 2 mg/ kg/ siegħa kull 30 minuta jekk ma jkun hemm l- ebda sinjali ta ’ reazzjonijiet assoċjati ma ’ l- infużjoni (IARs) sakemm tintlaħaq rata massima ta ’ 7 mg/ kg/ siegħa.
IARs are described in section 4.8.
L- IARs huma deskritti f’ sezzjoni 4. 8.
Posology for children, adolescents, adults and elderly:
Pożoloġija għat- tfal, adolexxenti, adulti u anzjani:
The safety and efficacy of Myozyme have been primarily evaluated in children with ages ranging from infancy to adolescence.
Is- sigurtà u l- effikaċja ta ’ Myozyme kienu primarjament evalwati fi tfal ta ’ età li tvarja mit- tfulija sa l- adolexxenza.
There is no evidence for special considerations when Myozyme is administered to children, adolescents, adults or elderly patients.
M’ hemm l- ebda evidenza għal konsiderazzjonijiet speċjali meta Myozyme jingħata lit- tfal, adolexxenti, adulti jew pazjenti anzjani.
The safety and efficacy of Myozyme in patients with renal or hepatic insufficiency have not been evaluated and no specific dosage regimen can be recommended for these patients.
Is- sigurtà u l- effikaċja ta ’ Myozyme f’ pazjenti b’ insuffiċjenza renali jew epatika ma kinux evalwati, u l- ebda kors ta ’ dożaġġ speċifiku ma jista ’ jkun rakkomandat għal dawn il- pazjenti.
2 Patient response to treatment should be routinely evaluated based on a comprehensive evaluation of all clinical manifestations of the disease.
2 Ir- rispons tal- pazjent għall- kura għandu jkun evalwat fuq bażi ta ’ rutina, ibbażat fuq evalwazzjoni komprensiva tal- manifestazzjonijiet kliniċi kollha tal- marda.
Hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients.
Sensittività eċċessiva (reazzjoni anafilattika) għas- sustanza attiva jew għal xi sustanzi mhux attivi.
Life-threatening anaphylactic reactions, including anaphylactic shock, have been observed in infantile and late onset patients during Myozyme infusions (see section 4.8).
Reazzjonijiet anafilattiċi ta ’ periklu għall- ħajja, li jinkludu xokk anafilattiku, kienu osservati f pazjenti li fihom il- marda bdiet fl- infanzja u dawk li fihom il- marda bdiet tard fil- ħajja waqt l- infużjonijiet ta ’ Myozyme (ara sezzjoni 4. 8).
Because of the potential for severe infusion associated reactions, appropriate medical support measures should be readily available when Myozyme is administered.
Minħabba l- potenzjal għal infużjoni severa marbuta mar- reazzjonijiet, miżuri adattati ta ’ sapport mediku għandhom ikunu disponibbli fil- pront meta jingħata Myozyme.
If severe or anaphylactic reactions occur, immediate discontinuation of Myozyme infusion should be considered and appropriate medical treatment should be initiated.
Jekk iseħħu reazzjonijiet anafilattiċi severi, it- twaqqif immedjat ta ’ l- infużjoni ta ’ Myozyme għandu jkun ikkunsidrat, u kura medika adattata għandha tinbeda.
The current medical standards for emergency treatment of anaphylactic reactions are to be observed.
L- istandards mediċi kurrenti għal kura ta ’ emerġenza ta ’ reazzjonijiet anafilattiċi għandhom ikunu osservati.
Approximately half of the patients treated with Myozyme in infantile onset clinical studies developed infusion associated reactions (IARs), defined as any related adverse event occurring during the infusion or during the hours following infusion.
Madwar nofs il- pazjenti kkurati b’ Myozyme fi studji kliniċi fuq pazjenti li fihom il- marda bdiet fl - infanzja, żviluppaw reazzjonijiet assoċjati mal- infużjoni, IARs, definiti bħala kwalunkwe avveniment avvers relatat li seħħ waqt l- infużjoni jew matul is- sigħat ta ’ wara l- infużjoni.
Some reactions were severe (see section 4.8).
Xi reazzjonijiet kienu severi (ara sezzjoni 4. 8).
A tendency was observed in infantile patients treated with a higher dose (40 mg/ kg) to experience more symptoms when developing IARs.
Kienet osservata tendenza f’ pazjenti li fihom il- marda bdiet fl- infanzja, ikkurati b’ doża ogħla (40 mg/ kg) li jkollhom aktar sintomi meta jiżviluppaw l- IARs.
Infantile onset patients who develop high antibody titres appear to be at higher risk for developing more frequent IARs.
Pazjenti li fihom il- marda bdiet fl- infanzja li jiżviluppaw titres ta ’ antikorpi għoljin, jidhru li huma f’ riskju ogħla li jiżviluppaw IARs b’ mod iktar frekwenti.
Patients with an acute illness (e. g. pneumonia, sepsis) at the time of Myozyme infusion appear to be at greater risk for IARs.
Pazjenti b’ mard akut (eż. pnewmonja, sepsis), meta jingħataw l- infużjoni b’ Myozyme, jidher li jkunu f’ riskju akbar għal IARs.
Careful consideration should be given to the patient’ s clinical status prior to administration of Myozyme.
Għandha tingħata konsiderazzjoni kbira lill- istat kliniku tal- pazjent qabel l- għoti ta ’ Myozyme.
Patients should be closely monitored and all cases of IARs, delayed reactions and possible immunological reactions should be reported.
Il- pazjenti għandhom ikunu mmonitorjati mill- qrib, u l- każijiet kollha ta ’ IARs, reazzjonijiet li jseħħu wara ċertu żmien u reazzjonijiet immunoloġiċi possibbli, għandhom ikunu rrappurtati.
Patients who have experienced IARs should be treated with caution when re-administering Myozyme (see section 4.3 and 4.8).
Pazjenti li kellhom IARs għandhom ikunu kkurati bl- attenzjoni meta jerġa ’ jingħata Myozyme (ara sezzjoni 4. 3 u 4. 8).
Mild and transient effects may not require medical treatment or discontinuation of the infusion.
Effetti ħfief u temporanji jista ’ ma jkollhomx bżonn ta ’ kura medika jew it- twaqqif ta ’ l- infużjoni.
Reduction of the infusion rate, temporary interruption of the infusion, or pre-treatment, generally with oral antihistamine and/ or antipyretics and/ or corticosteroids, has effectively managed most reactions.
It- tnaqqis tar- rata ta ’ l- infużjoni, l- interruzzjoni temporanja ta ’ l- infużjoni, jew il- kura minn qabel, ġeneralment b’ antistamina orali u/ jew mediċini kontra d- deni u/ jew kortikosterojdi, effettivament ikkontrollaw il- biċċa l- kbira tar- reazzjonijiet.
IARs may occur at any time during the infusion of Myozyme or generally up to 2 hours after, and are more likely with higher infusion rates.
L- IARs jistgħu jseħħu fi kwalunkwe ħin waqt l- infużjoni ta ’ Myozyme, jew ġeneralment sagħtejn wara, u x’ aktarx li se jseħħu iżjed b’ rata ogħla ta ’ l- infużjoni.
Patients with advanced Pompe disease may have compromised cardiac and respiratory function, which may predispose them to a higher risk of severe complications from infusion associated reactions.
Pazjenti li jinsabu fi stat avvanzat tal- marda ta ’ Pompe jista ’ jkollhom funzjoni kardijaka u respiratorja kompromessa, li tista ’ tippredisponihom għal riskju ogħla ta ’ kumplikazzjonijiet severi mill- infużjoni marbuta mar- reazzjonijiet.
Therefore, these patients should be monitored more closely during administration of Myozyme.
Għalhekk, dawn il- pazjenti għandhom ikunu mmonitorjati aktar mill- qrib matul l- għoti ta ’ Myozyme.
In clinical studies, the majority of patients developed IgG antibodies to rhGAA typically within 3 months of treatment.
Fi studji kliniċi, il- maġġoranza tal- pazjenti żviluppaw antikorpi IgG għal rhGAA, tipikament fi żmien 3 xhur minn meta bdiet il- kura.
Thus seroconversion is expected to occur in most patients treated with Myozyme.
Għaldaqstant, is- serokonverżjoni hi mistennija li sseħħ fil- biċċa l- kbira tal- pazjenti kkurati b’ Myozyme.
A tendency was observed for patients treated with a higher dose (40 mg/ kg) to develop higher titers of antibodies.
Kienet osservata tendenza għal pazjenti kkurati b’ doża ogħla (40 mg/ kg) li jiżviluppaw titers ogħla ta ’ antikorpi.
There does not appear to be a correlation between the onset of IARs and the time of antibody formation.
Ma jidher li hemm l- ebda korrelazzjoni bejn il- bidu ta ’ IARs u ż- żmien tal- formazzjoni ta ’ l- antikorpi.
A small number of the IgG positive patients evaluated tested positive for inhibitory effects on in vitro testing.
Instab li numru żgħir ta ’ pazjenti li kienu evalwati kienu pożittivi għal IgG, instab li kienu pożittivi għal effetti inibitorji meta sar ittestjar in vitro.
Due to the rarity of the condition and the limited experience to date, the effect of antibody formation on safety and efficacy is currently not fully established..
Minħabba r- rarità tal- kundizzjoni u l- esperjenza limitata s’ issa, l- effett tal- formazzjoni ta ’ l- antikorpi fuq is- sigurtà u l- effikaċja bħalissa mhuwiex stabbilit b’ mod sħiħ.
The probability of a poor outcome and of developing high and sustained antibody titers appears higher among CRIM-negative patients (Cross Reactive Immunologic Material; patients in whom no endogenous GAA protein was detected by Western blot analysis) than among CRIM-positive patients (patients in whom endogenous GAA protein was detected by Western blot analysis).
Il- probabbiltà ta ’ riżultat batut u li wieħed jiżviluppa titers għoljin u sostnuti ta ’ antikorpi tidher ogħla fost pazjenti li huma negattivi għal CRIM (Materjal Immunoloġiku Cross Reactive; pazjenti li fihom ma kienet osservata l- ebda proteina GAA endoġena mill- analiżi Western blot) milli fost pazjenti li kienu pożittivi għas- CRIM (pazjenti li fihom kienet osservata l- proteina GAA endoġena mill- analiżi Western blot).
However, high and sustained antibody titers also occur in some CRIM-positive patients.
Hu maħsub li l- kawża
The cause of a poor clinical outcome and of developing high and sustained antibody titers is thought to be multi-factorial.
3 ta ’ riżultat kliniku batut u li jiżviluppaw titers għoljin u sostnuti ta ’ antikorpi, hi multi- fattorjali.
Antibody titers should be regularly monitored.
It - titers ta ’ l- antikorpi għandhom ikunu mmonitorjati regolarment.
Transient nephrotic syndrome which resolved following temporary interruption of ERT was observed in one patient with infantile-onset Pompe disease who received very frequent dosing of rhGAA (10 mg/ kg 5 times weekly) over an extended period.
Kien osservat sindrome nefrotiku temporanju li fieq wara l- interruzzjoni temporanja ta ’ ERT f’ pazjent wieħed li kellu l- marda ta ’ Pompe li bdiet fl- infanzja, li rċieva dożaġġ frekwenti ħafna ta ’ rhGAA (10 mg/ kg 5 darbiet fil- ġimgħa) fuq perjodu twil ta ’ żmien.
No formal drug-drug interactions studies have been carried out with alglucosidase alfa.
Ma saru l- ebda studji formali b’ alglucosidase alfa dwar l- interazzjonijiet bejn mediċina u oħra.
Because it is a recombinant human protein, alglucosidase alfa is an unlikely candidate for cytochrome P450 mediated drug-drug interactions.
Minħabba li hu proteina umana rikombinanti, alglucosidase alfa mhux mistenni li jikkawża interazzjonijiet bejn mediċina u oħra medjati minn ċitokrom P450.
Myozyme should not be used during pregnancy unless clearly necessary.
Myozyme m’ għandux jintuża waqt it- tqala jekk m’ hemmx bżonn ċar.
Alglucosidase alfa may be excreted in breast milk.
Alglucosidase alfa jista ’ jitneħħa fil- ħalib tas- sider.
Because there are no data available on effects in neonates exposed to alglucosidase alfa via breast milk, it is recommended to stop breast-feeding when Myozyme is used.
Minħabba li m’ hemm l- ebda informazzjoni disponibbli fuq l- effetti fi trabi tat- twelid esposti għal alglucosidase alfa permezz tal- ħalib tas- sider, hu rakkomandat li t- treddigħ jitwaqqaf meta jintuża Myozyme.
In clinical trials, 39 infantile-onset patients were treated with Myozyme for more than three years (168 weeks with a median of 121 weeks; see section 5.1).
Fi provi kliniċi, 39 pazjent li fihom il- marda bdiet fl- infanzja, kienu kkurati b’ Myozyme għal iktar minn tliet snin (168 ġimgħa b’ medjan ta ’ 121 ġimgħa; ara sezzjoni 5. 1).
Most adverse events reported in these 39 patients were due to manifestations of Pompe disease and not related to the administration of Myozyme.
Il- biċċa l- kbira ta ’ l - avvenimenti avversi rrappurtati f’ dawn id- 39 pazjent kienu minħabba manifestazzjonijiet tal- marda ta ’ Pompe u ma kinux relatati ma ’ l- għoti ta ’ Myozyme.
Adverse Drug Reactions (ADRs) are listed in Table 1 by System Organ Class.
Reazzjonijiet Avversi tal- Mediċina (ADRs) huma elenkati f’ Tabella 1 skond il- Klassi ta ’ l- Organi tas- Sistema.
The ADRs listed are reported in more than 1 patient and shown as percentage of patients experiencing the ADR with the absolute number of patients in brackets.
L- ADRs elenkati huma rrappurtati f’ iktar minn pazjent wieħed u jintwerew bħala perċentwali ta ’ pazjenti li jkollhom l- ADR bin- numru assolut ta ’ pazjenti fil- parentesi.
ADRs were mostly mild to moderate in intensity and almost all occurred during the infusion or during the 2 hours following the infusion (infusion associated reactions, IARs).
L- ADRs kienu l- iktar minn ħfief sa moderati fl- intensità u kważi kollha seħħew waqt l- infużjoni jew matul is- sagħtejn ta ’ wara l- infużjoni (reazzjonijiet assoċjati mal - infużjoni, IARs).
Serious infusion reactions including urticaria, rales, tachycardia, decreased oxygen saturation, bronchospasm, tachypnea, periorbital edema and hypertension have been reported.
Reazzjonijiet serji għall- infużjoni kienu jinkludu urtikarja, ħsejjes tal- pulmun, takikardija, tnaqqis fis- saturazzjoni tal- ossiġnu, bronkospażmu, takipnea, edema periorbitali, u pressjoni għolja kienu rrappurtati
Adverse Drug Reactions by System Organ Class in more than one patient.
Reazzjonijiet Avversi tal- Mediċina skond il- Klassi ta ’ l- Organi tas- Sistema f’ iktar minn pazjent wieħed.
Frequency (no. of patients) N = 39
Frekwenza (numru ta ’ pazjenti) N = 39
Psychiatric disorders Nervous system disorders Cardiac disorders
Disturbi psikjatriċi
Agitation Tremor Tachycardia Cyanosis
Disturbi fis- sistema nervuża
5% (2 pts) 5% (2 pts) 10% (4 pts) 5% (2 pts)
10% (4 pazjenti)
Flushing Hypertension Pallor
5% (2 pazjenti) 13% (5 pazjenti)
13% (5 pts) 8% (3 pts) 5% (2 pts)
8% (3 pazjenti) 5% (2 pazjenti) 13% (5 pazjenti)
Respiratory, thoracic and mediastinal Cough disorders
Disturbi gastro- intestinali
13% (5 pts)
13% (5 pazjenti) 10% (4 pazjenti)
Tachypnoea Gastrointestinal disorders Vomiting Retching Nausea Skin and subcutaneous tissue Urticaria disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
13% (5 pts) 10% (4 pts) 5% (2 pts) 5% (2 pts) 18% (7 pts)
5% (2 pazjenti) 5% (2 pazjenti) 18% (7 pazjenti)
Rash Rash macular Erythema Rash maculo-papular Rash papular Pruritis General disorders and administration Pyrexia site conditions
Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
15% (6 pts) 5% (2 pts) 8% (3 pts) 8% (3 pts) 5% (2 pts) 5% (2 pts) 28% (11 pts)
15% (6 pazjenti) 5% (2 pazjenti) 8% (3 pazjenti) 8% (3 pazjenti) 5% (2 pazjenti) 5% (2 pazjenti) 28% (11- il pazjent)
Irritability Chills Investigations Oxygen saturation decreased Blood pressure increased Body temperature increased Heart rate increased
Irritabilità Tertir Tnaqqis fis- saturazzjoni ta ’ l - ossiġnu Żieda fil- pressjoni tad- demm
5% (2 pts) 5% (2 pts) 18% (7 pts) 5% (2 pts) 5% (2 pts) 5% (2 pts)
5% (2 pazjenti) 5% (2 pazjenti) 18% (7 pazjenti) 5% (2 pazjenti)
A limited number of patients with late-onset Pompe disease (see section 5.1) have been treated with Myozyme.
Numru limitat ta ’ pazjenti li fihom il- marda ta ’ Pompe bdiet tard fil- ħajja (ara sezzjoni 5. 1) kienu kkurati b’ Myzozyme.
ADRs reported in 2 of 9 late-onset patients treated with Myozyme for up to 1 year in 3 different studies included increased heart rate, hypertension, headache, peripheral coldness, paresthesia, flushing, infusion site pain, infusion site reaction, increased blood pressure and dizziness.
ADRs irrappurtati fi 2 minn 9 pazjenti li fihom il- marda ta ’ Pompe bdiet tard fil - ħajja, ikkurati b’ Myozyme sa sena fi 3 studji differenti kienu jinkludu żieda fir- rata ta ’ taħbit tal- qalb, pressjoni għolja, uġigħ ta ’ ras, kesħa periferali, parestesija, fwawar, uġigħ fis- sit ta ’ l- infużjoni, reazzjoni fis- sit ta ’ l- infużjoni, żieda fil- pressjoni tad- demm u sturdament.
The 2 late onset patients did not experience the same ADRs.
Iż- 2 pazjenti li fihom il - marda ta ’ Pompe bdiet tard fil- ħajja, ma kellhomx l- istess ADRs.
The ADRs were mild in intensity and assessed as an IAR.
L- ADRs kienu ħfief fl- intensità u kienu evalwati bħala IAR.
IARs in patients treated with Myozyme in clinical studies and expanded access programs and reported in more than 1 patient included rash, flushing, urticaria, pyrexia, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, increased blood pressure, cyanosis, hypertension, irritability, pallor, pruritus, retching, chills, tremor, hypotension, heart rate increased, bronchospasm, erythema, face edema, feeling hot, headache, hyperhidrosis, lacrimation increased, livedo reticularis, nausea, periorbital edema, restlessness and wheezing.
IARs f’ pazjenti kkurati b’ Myozyme fi studji kliniċi u fi programmi b’ aċċess imkabbar, u li kienu rrappurtati f’ aktar minn pazjent wieħed, li jinkludu raxx, fwawar, urtikarja, deni, sogħla, takikardija, tnaqqis fis- saturazzjoni ta ’ l- ossiġnu, rimettar, takipnea, aġitazzjoni, żieda fil- pressjoni tad- demm, ċijanosi, pressjoni għolja, irritabilità, sfurija, ħakk, dardir, tertir, rogħda, pressjoni baxxa, żieda fir- rata tat- taħbit tal- qalb, bronkospażmu, eritema, edema fil- wiċċ, tħoss is- sħana, uġigħ ta ’ ras, iperidrosi, żieda fil- produzzjoni tad- dmugħ, livedo reticularis, nawseja, edema periorbitali, nuqqas ta ’ kwiet
Those IARs reported as severe in more than 1 patient included pyrexia, decreased oxygen saturation, tachycardia, cyanosis and hypotension.
Dawk l- IARs irrappurtati li kienu bħala severi f’ iktar minn pazjent wieħed kienu jinkludu deni, tnaqqis fis- saturazzjoni ta ’ l- ossiġnu, takikardija, ċijanosi u pressjoni baxxa.
A single event of angioneurotic edema of severe intensity has been reported.
Avveniment wieħed ta ’ edema anġjonewrotika ta ’ intensità severa kien irrappurtat.
A small number of patients (< 1%) in clinical trials and in the commercial setting developed anaphylactic shock and/ or cardiac arrest during Myozyme infusion that required life-support measures.
Numru żgħir ta ’ pazjenti (< 1%) fi provi kliniċi u fi sfond kummerċjali, żviluppaw xokk anafilattiku u/ jew waqfien kardijaku waqt l- infużjoni b’ Myozyme, li kienu jeħtieġu miżuri ta ’ sapport tal- ħajja.
Reactions generally occurred shortly after initiation of the infusion.
Ir- reazzjonijiet ġeneralment seħħew ftit wara l- bidu tal- infużjoni.
Patients
Il- pazjenti kellhom varjetà kbira ta ’ sinjali u sintomi, li primarjament kienu respiratorji, kardjovaskulari, edematużi u/ jew tal- ġilda fin- natura tagħhom (ara Sezzjoni 4. 4).
5 with moderate to severe or recurrent IARs have been evaluated for Myozyme specific IgE antibodies; some patients tested positive including one patient who experienced an anaphylactic reaction.
Pazjenti b’ IARs moderati sa severi jew rikorrenti kienu evalwati għal antikorpi IgE li huma speċifiċi għal Myozyme; xi pazjenti ttestjaw pożittivi, li jinkludu pazjent wieħed li kellu reazzjoni anafilattika.
In clinical studies doses up to 40 mg/ kg body weight were used.
Fi studji kliniċi, intużaw dożi sa 40 mg/ kg ta ’ piż tal - ġisem.
Alimentary tract and metabolism products – enzymes.
Prodotti għall- passaġġ ta ’ l- ikel u tal- metaboliżmu – enzimi.
A16AB07 alglucosidase alfa.
A16AB07 alglucosidase alfa.
Alglucosidase alfa is a recombinant form of human acid α -glucosidase and is produced by recombinant DNA technology using Chinese Hamster Ovary (CHO) cell culture.
Alglucosidase alfa hu forma rikombinanti ta ’ acid α- glucosidase uman u hu magħmul minn teknoloġija DNA rikombinanti bl- użu ta ’ koltura taċ- ċelluli ta ’ l- Ovarju tal- Ħamster Ċiniż (CHO).
Pompe disease Pompe disease is a rare, progressive and fatal metabolic myopathy with an estimated global incidence of 1 in 40,000 births.
Il- marda ta ’ Pompe Il- marda ta ’ Pompe hi mijopatija metabolika rari, progressiva u fatali b’ inċidenza globali stmata ta ’ 1 minn kull 40, 000 twelid.
Other names for Pompe disease include glycogen storage disease type II (GSD- II), acid maltase deficiency (AMD) and glycogenosis type II.
Ismijiet oħrajn għall- marda ta ’ Pompe jinkludu l- marda tal- ħażna ta ’ glycogen ta ’ tip II (GSD- II), defiċjenza ta ’ acid maltase (AMD) u glikoġenesi ta ’ tip II.
Pompe disease belongs to the lysosomal storage disorders as it is caused by a deficiency of a naturally-occurring lysosomal hydrolase, acid α - glucosidase (GAA) that degrades lysosomal glycogen to glucose.
Il- marda ta ’ Pompe tappartieni għad- disturbi tal- ħażna lisosomali għax hi kkawżata minn defiċjenza ta ’ hydrolase lisosomali li sseħħ b’ mod naturali, acid α- glucosidase (GAA) li jiddegrada glycogen lisosomali għal glucose.
Deficiency of this enzyme leads to glycogen accumulation in various tissues, particularly cardiac, respiratory and skeletal muscle, leading to the development of hypertrophic cardiomyopathy and progressive muscle weakness, including impairment of respiratory function.
Id- defiċjenza ta ’ din l- enzima twassal għall- akkumulazzjoni tal- glycogen f’ diversi tessuti, partikularment fil- muskoli kardijaċi, respiratorji u skeletriċi, li twassal għall- iżvilupp ta ’ kardjomijopatija ipertrofika u dgħjufija progressiva fil- muskoli, li tinkludi indeboliment tal- funzjoni respiratorja.
The clinical presentation of Pompe disease can be described as a spectrum of disease which ranges from a rapidly-progressing infantile-onset form (onset of symptoms of Pompe disease typically within the first year of life and a very short expected life-span) to a less rapidly-progressing late-onset form.
Il- preżentazzjoni klinika tal- marda ta ’ Pompe tista ’ tkun deskritta bħala l- medda tal- marda li tvarja mill- forma tal- marda li tibda fl- infanzja li jkollha progressjoni mgħaġġla (il- bidu tas- sintomi tal- marda ta ’ Pompe li tipikament jidhru fl- ewwel sena tal- ħajja u b’ tul ta ’ ħajja mistenni li jkun qasir ħafna), sal- forma tal- marda li tibda tard fil- ħajja, bi progressjoni inqas mgħaġġla.
The infantile-onset form of Pompe disease is characterised by massive deposition of glycogen in the heart, and skeletal muscle always resulting in rapidly progressive cardiomyopathy, generalised muscle weakness and hypotonia.
F’ pazjenti li fihom il- marda ta ’ Pompe bdiet fl- infanzja, din tkun ikkaratterizzata minn depożitu massiv ta ’ glycogen fil- qalb u fil- muskoli skeletriċi, li dejjem jirriżulta f’ kardjomijopatija progressiva mgħaġġla, dgħjufija ġeneralizzata fil- muskoli u ipotonija.
Motor development is often completely arrested, or if motor milestones are achieved, they are subsequently lost.
L- iżvilupp tal- moviment ta ’ spiss jieqaf kompletament, jew jekk il- milestones tal- moviment jintlaħqu, dawn sussegwentement jintilfu.
Death typically occurs due to cardiac and/ or respiratory failure before the age of one year.
Il- mewt tipikament isseħħ minħabba insuffiċjenza kardijaka u/ jew tan- nifs qabel ma l- pazjent jagħlaq sena.
In a retrospective natural history study in patients with infantile-onset Pompe disease (n=168), the median age at onset of symptoms was 2.0 months and the median age of death was 9.0 months.
Fi studju retrospettiv dwar l- istorja naturali f’ pazjenti li fihom il- marda ta ’ Pompe bdiet fl- infanzja (n=168), il- medjan ta ’ l- età meta bdew is- sintomi kien ta ’ xahrejn, u l- medjan ta ’ l- età tal- mewt kien ta ’ 9. 0 xhur.
Kaplan-Meier survival rates at 12, 24 and 36 months of age were 26%, 9% and 7%, respectively.
Ir- rati ta ’ sopravivenza ta ’ Kaplan- Meier fi 12, 24 u 36 xahar ta ’ età kienu ta ’ 26%, 9% u 7%, rispettivament.
A non-typical, more slowly progressive form of infantile-onset Pompe disease has been described which is characterised by a less severe cardiomyopathy and consequently a more prolonged survival.
Forma mhux tipika, li jkollha progressjoni aktar bil- mod, tal- marda ta ’ Pompe li tibda fl- infanzja kienet deskritta, li hi kkaratterizzata minn kardjomijopatija inqas severa, u konsegwentement sopravivenza li ddum aktar.
The late-onset form of Pompe disease manifests during infancy, childhood, adolescence or even adulthood and is much less rapidly progressive than the infantile-onset form.
6 Il- forma tal- marda ta ’ Pompe li tibda aktar tard fil- ħajja tkun osservata matul l- infanzja, it- tfulija, l - adolexxenza jew meta persuna ssir adulta, u hi ħafna inqas progressiva b’ mod mgħaġġel mill- forma tal- marda li tibda fl- infanzja.
Usually, it is characterised by the presence of sufficient residual GAA activity to preclude the development of cardiomyopathy, however some cardiac involvement has been reported in up to approximately 4% of patients with late-onset Pompe disease.
Normalment, din tkun ikkaratterizzata mill- preżenza ta ’ attività GAA residwa suffiċjenti li tipprekludi l- iżvilupp ta ’ kardjomijopatija; madankollu xi involviment kardijaku kien irrappurtat f’ sa madwar 4% tal- pazjenti li fihom il- marda ta ’ Pompe bdiet tard fil- ħajja.
Patients with late-onset Pompe disease typically present with progressive myopathy, predominantly of the proximal muscles in the pelvic and shoulder girdles, and varying degrees of respiratory involvement, ultimately progressing to profound disability and/ or the need for ventilatory support.
Pazjenti li fihom il- marda ta ’ Pompe bdiet tard fil- ħajja, tipikament ikollhom mijopatija progressiva, fil- biċċa l- kbira tagħha fil- muskoli prossimali fiċ- ċinturi pelviċi u ta ’ l- ispallejn, u bi gradi varji ta ’ involviment respiratorju, li fl- aħħar mill- aħħar il- marda tiżviluppa f’ diżabilità profonda u/ jew fil - ħtieġa għal sapport bil- ventilatur.
The time course of disease progression is extremely variable and not predictable, with some patients experiencing a rapid deterioration in skeletal and respiratory muscle function leading to loss of
Pazjenti oħrajn ikollhom deterjorament inqas mgħaġġel.
6 ambulation and respiratory failure, others progressing less rapidly, and yet others presenting with a dissociation in the progression of skeletal and respiratory muscle involvement.
Oħrajn ikollhom dissoċjazzjoni fil- progressjoni ta ’ l- involviment skeletriku u tal- muskoli respiratorji.
It is postulated that Myozyme will restore lysosomal GAA activity resulting in stabilisation or restoration of cardiac and skeletal muscle function (including respiratory muscles).
Hu kkalkulat li Myozyme ser ireġġa ’ lura għan- normal l- attività lisosomali GAA li tirriżulta fl - istabbilizzazzjoni jew fir- restituzzjoni tal- funzjoni kardijaka u tal- muskoli skeletriċi (li tinkludi l - muskoli respiratorji).
Due to the blood- brain barrier effect and the enzyme’ s size, uptake of alglucosidase alfa in the central nervous system is unlikely.
Minħabba l- effett ta ’ l- ostakolu demm- moħħ u d- daqs ta ’ l- enzima, it- teħid ta ’ alglucosidase alfa fis- sistema nervuża ċentrali mhuwiex mistenni.
Infantile-onset Pompe disease; clinical trial in patients aged 6 months or less The safety and efficacy of Myozyme was assessed in a pivotal, randomised, open-label, historically- controlled clinical trial of 18 non-ventilated infantile-onset patients aged 6 months or less at the onset of treatment.
Is- sigurtà u l- effikaċja ta ’ Myozyme kienet evalwata fi prova klinika importanti ħafna, randomised, open- label, ikkontrollata storikament, fuq 18- il pazjent li ma kinux ivventilati li fihom il- marda bdiet fl- infanzja, li kelhom 6 xhur jew inqas fil- bidu tal- kura.
The untreated historical cohort was matched to the pivotal study population and was derived from a retrospective natural history study (n=42) in patients with infantile-onset Pompe disease.
Il- koorti storiku mhux ikkurat kien imqabbel ma ’ l- istudju importanti ħafna u kien miksub minn studju retrospettiv ta ’ l- istorja naturali (n=42) f’ pazjenti li fihom il- marda ta ’ Pompe bdiet fl- infanzja.
Patients were randomized to receive either 20 mg/ kg or 40 mg/ kg every two weeks for a period of 52 weeks.
Il- pazjenti kienu randomized biex jirċievu jew 20 mg/ kg jew 40 mg/ kg kull ġimagħtejn għal perjodu ta ’ 52 ġimgħa.
After a minimum of 52 weeks, 16 of these 18 patients were enrolled in an extension study to receive continued treatment at the same dose for a total duration of up to three years (150 weeks).
Wara minimu ta ’ 52 ġimgħa, 16 minn dawn it- 18- il pazjent kienu rreġistrati fi studju ta ’ estensjoni biex jirċievu kura kontinwa fl - istess doża għal tul ta ’ żmien sa tliet snin (150 ġimgħa).
The primary endpoint was the proportion of patients who were alive and free of invasive ventilator support.
Ir- riżultat aħħari primarju kien il- proporzjon ta ’ pazjenti li kienu ħajjin u ħielsa minn sapport invażiv bil- ventilatur.
However, the invasive ventilator-free survival was not recorded in the untreated historical cohort and a comparison of this endpoint is not possible.
Madankollu, is- sopravivenza ħielsa mill- ventilazzjoni invażiva ma kinitx irrekordjata fil- koorti storiku mhux ikkurat u l- paragun ta ’ dan ir- riżultat aħħari mhuwiex possibbli.
After 52 weeks of treatment, all 18 patients treated with Myozyme were alive and 15 of these 18 patients were alive and free of invasive ventilatory support whereas 1 of 42 patients in the untreated historical cohort was alive at 18 months of age.
Wara 52 ġimgħa ta ’ kura, it- 18- il pazjent kollha kkurati b’ Myozyme kienu ħajjin, u 15 minn dawn it- 18- il pazjent kienu ħajjin u ħielsa minn sapport ta ’ ventilazzjoni invażiva, filwaqt li 1 minn 42 pazjent fil - koorti storiku mhux ikkurat kien ħaj meta kellu 18- il xahar.
Two patients died and did not enter into the extension study.
Żewġ pazjenti mietu u ma daħlux fl - istudju ta ’ estensjoni.
After 104 weeks of treatment, all 16 patients who enrolled in the extension study were alive and 10 of these 16 patients were free of invasive ventilatory support.
Wara 104 ġimgħat ta ’ kura, is- 16- il pazjent kollha li rreġistraw fl- istudju ta ’ estensjoni kienu ħajjin, u 10 minn dawn is- 16- il pazjent kienu ħielsa minn sapport ventilatorju invażiv.
At the end of the study (with individual patient treatment durations ranging from 60 to 150 weeks; mean follow-up period of 119 weeks) 14 of 16 patients were alive and 9 of 16 patients were alive and free of invasive ventilatory support.
Fit- tmiem tal- istudju (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 60 sa 150 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 119- il ġimgħa) 14 minn 16- il pazjent kienu ħajjin, u 9 minn 16- il pazjent kienu ħajjin u ħielsa minn sapport ta ’ ventilazzjoni invażiva.
One additional patient died after study end and another one after withdrawal from the study.
Pazjent ieħor miet wara t- tmiem tal- istudju u ieħor miet wara li waqqaf jipparteċipa fl- istudju.
Comparison of survival curves from time of diagnosis versus the untreated historical cohort was made using a Cox proportional hazards regression analysis.
Il- paragun tal- kurvi tas- sopravivenza miż- żmien tad- dijanjosi kontra koorti storiku mhux ikkurat, saret permezz ta ’ analiżi tar- rigressjoni tal- perikli proporzjonali ta ’ Cox.
Patients treated with Myozyme demonstrated prolonged survival as compared to survival in an untreated historical cohort (see Table 2).
Il- pazjenti kkurati b’ Myozyme urew sopravivenza mtawla meta mqabbla mas- sopravivenza fil- koorti storiċi li ma kinux ikkurati (ara Tabella 2).
7 Table 2:
7 Tabella 2:
Results for endpoint survival using the Cox regression model
Riżultati għas- sopravivenza tar- riżultati aħħari ta ’ l- istudju bl- użu tal- mudell tar- rigressjoni ta ’ Cox Proporzjon Pazjenti Komparatur Kkurati Storiku tar -
Historical
tal- Periklu tal- Kura -
95%
95% Intervall tal -
Reference
Referenza
Effect Hazard Confidence
Riżultat aħħari
Patients
Effett
Comparator
Kunfidenza
N=18
N=42 N=18
N=42
Sopravivenza
Survival
0. 05
0.05
(0. 015, 0. 147)
(0.015, 0.147) < 0.0001
< 0. 0001
Results are from a Cox proportional hazards regression analysis which includes treatment as a time-varying covariate, and also includes age of diagnosis and age at symptom onset.
Ir- riżultati huma minn analiżi tar- rigressjoni tal- perikli proporzjonali ta ’ Cox li tinkludi l - kura bħala ko- varjant li jvarja maż- żmien, u tinkudi wkoll l- età tad- dijanjosi u l- età meta bdew is - sintomi.
Subjects were aged 6 months or less at the onset of treatment.
Il- pazjenti kellhom 6 xhur jew inqas meta bdiet il- kura.
Subjects in the untreated historical cohort were born in 1993 or later.
Il- pazjenti fil- koorti storiku mhux ikkurat twieldu fl- 1993 jew wara.
Echocardiographic indices of cardiomyopathy improved as measured by a decrease in left ventricular mass (LVM).
L- indiċi ekokardjografiċi tal- kardjomijopatija tjiebu hekk kif imkejla minn tnaqqis fil- piż ventrikulari tax- xellug (LVM).
After 52 weeks of treatment, LVM decreased from baseline in all 14 patients with available data and was within normal limits in 3 of 14 patients.
Wara 52 ġimgħa ta ’ kura, l- LVM naqas mil- linja bażi fl- 14- il pazjent kollha b’ dejta disponibbli, u kienu fil- limiti normali fi 3 minn 14- il pazjent.
After the first year (64 up to 130 weeks) of treatment LVM further decreased in 8 patients.
Wara l- ewwel sena (64 sa 130 ġimgħa) ta ’ kura, l- LVM naqas b’ mod ulterjuri fi 8 pazjenti.
At 104 weeks of treatment LVM assessments were available for 8 patients, of which 5 decreased to within normal limits.
Wara 104 ġimgħat ta ’ kura, evalwazzjonijiet tal - LVM kienu disponibbli għal 8 pazjenti, li minnhom 5 naqsu sal- limiti normali.
As measured by motor performance age-equivalent scores of the Alberta Infant Motor Scale (AIMS), seven of the 18 patients made motor development gains during the study and were walking independently by the last study assessment (with individual patient treatment durations ranging from 52 to 130 weeks; mean follow-up period of 94 weeks).
Hekk kif imkejla permezz tal- punteġġi tal- prestazzjoni li huma ekwivalenti għall- età tal- Alberta Infant Motor Scale (AIMS), seba ’ mit- 18- il pazjent kisbu titjib fl- iżvilupp tal- moviment matul l- istudju u kienu jimxu indipendentement sal- aħħar evalwazzjoni tal- istudju (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 52 sa 130 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 94 ġimgħa).
An additional 4 patients made motor development gains during the study and were sitting independently by the last study assessment (with individual patient treatment durations ranging from 78 to 130 weeks; mean follow-up period of 110 weeks), although they did not have functional use of the legs.
4 pazjenti addizzjonali kisbu titjib fl- iżvilupp tal- moviment matul l- istudju u kienu joqogħdu bilqiegħda indipendentement sal- aħħar evalwazzjoni tal- istudju (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 78 sa 130 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 110 ġimgħa), għalkemm ma kellhomx użu funzjonali tar- riġlejn.
The remaining 7 patients made no clinically significant motor gains or were unable to sustain the motor gains made and had very limited motor movement by the last study assessment (with individual patient treatment durations ranging from 52 to 142 weeks; mean follow-up period of 103 weeks).
Il- bqija tas- 7 pazjenti ma kisbu l- ebda titjib tal- moviment li kien klinikament sinifikanti, jew ma kinux kapaċi jżommu t- titjib tal- moviment miksub, u kellhom moviment motoreju limitat ħafna sal- aħħar evalwazzjoni tal- istudju (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 52 sa 142 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 103 ġimgħat).
After 52 weeks of treatment 14 of 18 patients (77.8%) had maintained or improved weight-for-age percentiles (above the 3rd percentile), 14 of 15 patients (93.3%) were above the 3rd percentile for length and 12 of 15 patients (80.0%) were above the 3rd percentile for head circumference.
Wara 52 ġimgħa ta ’ kura, 14 minn 18- il pazjent (77. 8%) żammew jew tejbu l- percentiles piż- età (’ il fuq mit- 3et percentile), 14 minn 15- il pazjent (93. 3%) kienu ’ l fuq mit- 3et percentile għat- tul u 12 minn 15- il pazjent (80. 0%) kienu ’ l fuq mit- 3et percentile għaċ- ċirkonferenza tar- ras.
In the second year of treatment, 15 out of 17 patients had further improved weight-for-age percentiles (with individual patient treatment durations ranging from 78 to 142 weeks; mean follow-up period of 111 weeks), 10 out of 16 patients had further improved length-for-age percentiles (with individual patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 113 weeks) and 11 out of 15 patients had further improved head circumference-for-age percentiles (with individual patient treatment durations ranging from 90 to 130 weeks; mean follow-up period of 110 weeks).
Fit- tieni sena tal - kura, 15 minn 17- il pazjent tejbu b’ mod ulterjuri l- percentiles piż- età (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 78 sa 142 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 111- il ġimgħa), 10 minn 16- il pazjenti tejbu b’ mod ulterjuri l- percentiles tul- età (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 90 sa 130 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 113- il ġimgħa) u 11 minn 15- il pazjent tejbu b’ mod ulterjuri l- percentiles taċ- ċirkonferenza tar- ras meta mqabbla mal - età (bit- tul tal- kura ta ’ pazjenti individwali li varja minn 90 sa 130 ġimgħa; il- medja tal- perjodu follow- up kienet ta ’ 110 ġimgħat).
At 104 weeks of treatment, all 13 patients with available data had maintained or improved weight-for-age percentiles (above the 3rd percentile), all 12 patients with available data were above the 3rd percentile for length and all 12 patients with available data were above the 3rd percentile for head circumference.
Wara 104 ġimgħat ta ’ kura, it- 13- il pazjent kollha b’ dejta disponibbli żammew jew tejbu l- percentiles piż- età (’ il fuq mit- 3et percentile), it- 12- il pazjent kollha b’ dejta disponibbli kienu ’ l fuq mit- 3et percentile għat- tul, u t- 12- il pazjent kollha b’ dejta disponibbli kienu ’ l fuq mit- 3et percentile għaċ- ċirkonferenza tar- ras.