GSK ogłosiła, że Komisja Europejska udzieliła pozwolenia na dopuszczenie do obrotu dla produktu leczniczego Nucala® (mepolizumab) wskazanego w leczeniu uzupełniającym u dorosłych pacjentów z ciężką, oporną na leczenie astmą eozynofilową. W wyniku tej decyzji produkt leczniczy Nucala jest obecnie zatwierdzony do stosowania w 31 krajach europejskich podlegających Europejskiej Agencji Leków (EMA).

Produkt leczniczy Nucala to pierwszy i jedyny zatwierdzony na terenie Unii Europejskiej lek biologiczny działający na interleukinę-5 (IL-5), która odgrywa ważną rolę w regulowaniu funkcji eozynofili – komórek zapalnych, o których wiadomo, że odgrywają ważną rolę w astmie. Lek ten podaje się we wstrzyknięciu podskórnym, w stałej dawce 100 mg, co cztery tygodnie. Jest on uzupełnieniem normalnego schematu leczenia astmy ciężkiej, który obejmuje stosowanie przez pacjenta często wysokich dawek wziewnych glikokortykosteroidów oraz dodatkowych leków kontrolujących, w tym glikokortykosteroidów przyjmowanych doustnie1.

Pozwolenie na dopuszczenie do obrotu dla produktu leczniczego Nucala w UE stanowi istotny postęp  w leczeniu pacjentów z ciężką astmą eozynofilową, jak również umacnia firmę GSK na pozycji lidera w dziedzinie leczenia chorób układu oddechowego. Jesteśmy dumni z tego, że nasze prace w tej dziedzinie, mające na celu dokładniejsze wyjaśnienie roli eozynofilli w ciężkiej astmie, zaowocowały uzyskaniem rejestracji mepolizumabu jako pierwszego leku biologicznego anty-IL-5. Naszym celem jest zaoferowanie tego leku pacjentom możliwie jak najszybciej – powiedział Eric Dube, wiceprezes i dyrektor Globalnej Franczyzy Leków Układu Oddechowego GSK.

Główny badacz w pierwszym badaniu mającym na celu potwierdzenie koncepcji działania mepolizumabu, a zarazem badacz uczestniczący w badaniu fazy III MENSA, profesor Ian Pavord z Uniwersytetu w Oksfordzie, powiedział: – Pacjenci z ciężką, oporną na leczenie astmą eozynofilową nie są typowymi pacjentami z „astmą”. U osób tych utrzymanie kontroli nad chorobą jest trudne pomimo stosowania wysokich dawek leków przyjmowanych drogą wziewną. Szczególny problem w ich przypadku stanowią częste napady astmy, które mogą wymagać hospitalizacji. Wielu z tych pacjentów przyjmuje również w celu kontrolowania objawów, glikokortykosteroidy doustne, których stosowanie może prowadzić do wystąpienia działań niepożądanych, często bardzo uciążliwych dla pacjentów. Możliwość zaoferowania tym pacjentom leczenia działającego w sposób swoisty na podstawową przyczynę choroby będzie stanowiło  dla nich ważną opcję terapeutyczną.

W programie fazy IIb/III badań klinicznych mepolizumabu oceniano skuteczność i bezpieczeństwo stosowania tego leku u pacjentów z ciężką astmą. U wszystkich pacjentów w badaniach MEA115588 (MENSA) i MEA115575 (SIRIUS) liczba eozynofili (granulocytów kwasochłonnych) we krwi obwodowej była większa lub równa 150 komórek/μl w momencie rozpoczynania leczenia oraz większa lub równa 300 komórek/μl w ciągu ostatnich 12 miesięcy5,6.

Zatwierdzona w UE charakterystyka produktu leczniczego Nucala jest dostępna na stronie http://ec.europa.eu/health/documents/community-register/index_en.htm.

Informacje o astmie

Według aktualnych oszacowań na całym świecie żyją nawet 242 miliony osób z astmą7. U wielu z tych pacjentów istniejące metody leczenia, które jeśli są prawidłowo stosowne, są w stanie zapewnić wystarczającą kontrolę objawów choroby. Jednak u mniej niż 5% pacjentów występuje ciężka, oporna na leczenie astma, a istniejące metody leczenia nie zapewniają uzyskania kontroli jej objawów8.

Informacje o ciężkiej astmie i zapaleniu eozynofilowym

Ciężka astma jest zdefiniowana jako astma, która wymaga leczenia wysokimi dawkami glikokortykosteroidów wziewnych (GKS) w połączeniu z drugim lekiem kontrolującym objawy (i/lub glikokortykosteroidami podawanymi ogólnoustrojowo) w celu zapobiegania rozwojowi choroby „niekontrolowanej”, czyli takiej, która pozostaje „niekontrolowana” pomimo stosowania takiego leczenia9. Pacjentów z ciężką astmą często klasyfikuje się według długotrwałego stosowania glikokortykosteroidów doustnych (GKD). W podgrupie pacjentów z ciężką astmą nadmierna produkcja eozynofili (rodzaj krwinek białych) jest przyczyną stanu zapalnego w płucach, który może mieć wpływ na drogi oddechowe, ograniczając możliwość oddychania i zwiększając częstość występowania napadów astmy 2,10,11. Interleukina-5 (IL-5) jest głównym czynnikiem wzrostu, aktywacji i przeżycia eozynofili oraz stanowi podstawowy sygnał dla przemieszczania się eozynofili ze szpiku kostnego do płuc10,11,12,13.

Aby uzyskać więcej informacji, należy zapoznać się z opracowaną przez firmę GSK infografiką na temat ciężkiej astmy i roli eozynofili.

Informacje o produkcie leczniczym Nucala

Nucala to przeciwciało monoklonalne, które hamuje przyłączanie się IL-5 do jej receptorów na powierzchni eozynofili. Zahamowanie takiego wiązania IL-5 redukuje poziom eozynofili we krwi, tkankach i plwocinie1.

Program badań klinicznych fazy II/III oceniających mepolizumab obejmował dziewięć badań z udziałem łącznie 915 pacjentów z ciężką, oporną na leczenie astmą eozynofilową, którzy otrzymywali dawki mepolizumabu drogą podskórną lub dożylną podczas badań klinicznych trwających od 24 do 52 tygodni. W trzech kluczowych badaniach klinicznych – DREAM (MEA112997)14, MENSA (MEA115588)5 i SIRIUS (MEA115575)6 – określono profil skuteczności i bezpieczeństwa produktu Nucala u pacjentów z ciężką, oporną na leczenie astmą eozynofilową1.

Wniosek rejestracyjny dotyczący produktu leczniczego Nucala przedłożono do Europejskiej Agencji Leków w listopadzie 2014 roku i został on zatwierdzony w dniu 2 grudnia 2015 roku.

Inne działania rejestracyjne dotyczące mepolizumabu

Preparat Nucala został zatwierdzony w USA w dniu 4 listopada 2015 roku jako dodatkowe leczenie podtrzymujące dla pacjentów z ciężką astmą będących w wieku 12 lat lub starszych, z eozynofilowym fenotypem choroby. Pełna obowiązująca w USA informacja o produkcie jest dostępna jako Charakterystyka Produktu Nucala zatwierdzona w USA. W szeregu innych krajów, między innymi w Japonii, przedłożono wnioski rejestracyjne, które obecnie są rozpatrywane. W roku 2016 planuje się przedłożenie kolejnych wniosków rejestracyjnych.

Nucala® jest zarejestrowanym znakiem towarowym należącym do grupy spółek GSK.

Ważne informacje na temat bezpieczeństwa produktu leczniczego Nucala

Poniższe ważne informacje na temat bezpieczeństwa opierają się na europejskiej charakterystyce produktu leczniczego oraz na obowiązującej w USA charakterystyce produktu Nucala. Należy zapoznać się ze wszystkimi informacjami dotyczącymi bezpieczeństwa produktu Nucala zawartymi w charakterystyce produktu leczniczego.

Preparat Nucala jest przeciwwskazany u pacjentów, u których występuje nadwrażliwość na mepolizumab lub którąkolwiek substancję pomocniczą.

Preparatu Nucala nie należy stosować w leczeniu nagłych zaostrzeń astmy.

Podczas leczenia mogą wystąpić zdarzenia niepożądane związane z astmą oraz zaostrzenia. Pacjentów należy poinformować, że jeśli po rozpoczęciu leczenia produktem leczniczym Nucala nasilą się objawy astmy lub nie będą one prawidłowo kontrolowane, to należy zasięgnąć porady lekarskiej3,4.

Nie zaleca się nagłego przerwania podawania kortykosteroidów po rozpoczęciu leczenia produktem leczniczym Nucala. Jeśli to konieczne, dawki kortykosteroidów należy zmniejszać stopniowo pod kontrolą lekarza.

Po zastosowaniu produktu leczniczego Nucala występowały ostre i opóźnione, ogólnoustrojowe reakcje, w tym reakcje nadwrażliwości (np. pokrzywka, obrzęk naczynioruchowy, wysypka, skurcz oskrzeli, niedociśnienie). Reakcje te zazwyczaj występowały w ciągu kilku godzin od podania, ale w niektórych przypadkach ich wystąpienie było opóźnione (tj. zwykle w ciągu kilku dni). Reakcje te mogą wystąpić po raz pierwszy po długim czasie leczenia.

W kontrolowanych badaniach klinicznych odnotowano dwa ciężkie działania niepożądane (przypadki półpaśca) u pacjentów leczonych produktem Nucala, podczas gdy zdarzenia takie nie wystąpiły w grupie placebo. W przypadku wskazań medycznych należy rozważyć szczepienie przeciwko ospie wietrznej przed rozpoczęciem leczenia produktem Nucala.

Eozynofilia może być elementem odpowiedzi immunologicznej na niektóre zarażenia pasożytami jelitowymi. U pacjentów z istniejącymi wcześniej zarażeniami pasożytami jelitowymi, przed rozpoczęciem leczenia, należy zastosować leczenie przeciwpasożytnicze. Jeśli pacjenci zarażą się pasożytami jelitowymi w czasie leczenia produktem leczniczym Nucala i nie odpowiadają na leczenie przeciwpasożytnicze, należy rozważyć tymczasowe przerwanie leczenia produktem leczniczym.

Podczas badań klinicznych z udziałem pacjentów z ciężką, oporną na leczenie astmą eozynofilową, najczęściej zgłaszanymi działaniami niepożądanymi były: ból głowy, reakcje w miejscu wstrzyknięcia i ból pleców. Bóle głowy występowały bardzo często – z częstością ≥1/10. Częste działania niepożądane (występujące z częstością od ≥1/100 do <1/10) obejmowały: zakażenie dolnych dróg oddechowych, zakażenie dróg moczowych, zapalenie gardła, reakcje nadwrażliwości (ogólnoustrojowe, alergiczne), przekrwienie błony śluzowej nosa, bóle w nadbrzuszu, wyprysk, ból pleców, reakcje związane z podawaniem leków (niealergiczne ogólnoustrojowe), reakcje w miejscu wstrzyknięcia, gorączka.

Reakcje w miejscu wstrzyknięcia (np. ból, rumień, obrzęk, świąd i pieczenie) występowały u 8% pacjentów leczonych produktem Nucala w porównaniu z 3% pacjentów otrzymujących placebo.

 

Referencje:

1 Nucala Summary of Product Characteristics, 2015

2 Malinovschi A, et al. Exhaled nitric oxide and blood eosinophils independently associate with wheeze and asthma events in NHANES subjects. J Allergy Clin Immunol. 2013;132:821-827.

5 Ortega HG, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207.

6 Bel EL, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197.

7 Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:743–800

8 American Thoracic Society Workshop Report. Proceedings of the ATS workshop on refractory asthma: Current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med. 2000;162:2341-2351.

9 Chung KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–373

10 Rothenberg ME. Eosinophillia. N Engl J Med. 1998;338:1592-1600.

11Lopez AF, et al. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med.1988;167:219–224.

12Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013;13:9-22.

13 Kouro T, Takatsu T. IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol. 2009;21(12):1303–1309.

14 Pavord ID et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651-59


dostarczył infoWire.pl

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