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Etusivu » Tiedotteet » Terveys » Lancetissa julkaistu faasin 3 tutkimustuloksia Crohnin tautia sairastavien potilaiden vaikeiden perianaalifisteleiden hoidosta

Takeda Oy

Lancetissa julkaistu faasin 3 tutkimustuloksia Crohnin tautia sairastavien potilaiden vaikeiden perianaalifisteleiden hoidosta

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Julkaistu: 17.08.2016 klo 17:46
Julkaisija: Takeda Oy

Faasin 3 ADMIRE-CD-tutkimuksen tuloksia on julkaistu Lancetissa.1 24 viikon pituisessa satunnaistetussa, lumekontrolloidussa ja kaksoissokkoutetussa ADMIRE-CD-tutkimuksessa tutkittiin Cx601-valmisteen tehoa ja turvallisuutta Crohnin taudin vaikeahoitoisten perianaalifisteleiden hoidossa potilailla, joilla oli taustalla vähintään yksi epäonnistunut tavanomainen tai biologinen lääkehoito. Tutkimusvalmiste Cx601 on allogeeninen rasvan kantasoluja sisältävä suspensiovalmiste, joka annostellaan injektiona suoraan vaurioituneeseen kudokseen.

Tutkimuksessa ensisijaisen päätetapahtuman, yhdistetyn remission viikolla 24, saavutti tilastollisesti merkitsevästi suurempi määrä Cx601:llä hoidetuista kuin lumelääkettä saaneista potilaista: ITT-populaatiossa 53 potilasta 107:stä Cx601-ryhmän potilaasta (50 %) vs. 36 potilasta 105:stä lumeryhmän potilaasta (34 %) (97,5 % lv 0,2–30,3; p = 0,024). Päätetapahtumana käytetyssä yhdistetyssä remissiossa fistelien tulee olla sulkeutuneita sekä ulkoisesti että magneettikuvauksen perusteella. Tässä tutkimuksessa käytetty päätetapahtuman määritelmä on tiukempi kuin yleensä kliinisissä tutkimuksissa käytetty.2,3 Ensisijaisen päätetapahtuman lisäksi tutkimuksessa seurattiin perianaalisen Crohnin taudin aktiivisuusindeksiä (perianal disease activity index, PDAI) lähtötilanteessa ja tutkimuksen aikana. PDAI-arvon muutos oli Cx601-valmistetta saaneessa ryhmässä tilastollisesti merkitsevästi suurempi viikoilla 6, 12 ja 18. Viikolla 24 Cx601-valmisteella hoidetun ryhmän PDAI-keskiarvo (4,4) oli lähellä inaktiivisen perianaalitaudin kynnysarvoa (PDAI < 4), jonka saavuttaneet potilaat eivät tarvitse lääke- tai kirurgista hoitoa. Tutkimuksen aikana haittatapahtumat ja niiden vuoksi tapahtuneet tutkimuksen keskeyttämiset olivat yhtä yleisiä Cx601-valmisteella ja lumeella.

Japanilainen lääkeyhtiö Takeda ja belgialainen biolääkealan yhtiö TiGenix ovat aiemmin solmineet lisensointisopimuksen TiGenixin kehittämän kantasolupohjaisen Cx601-lääkkeen USA:n ulkopuolisten markkina-alueiden markkinointi- ja myyntioikeuksista. Cx601 on suunnattu Crohnin tautia sairastavilla potilailla esiintyvien perianaalisten fisteleiden hoitoon.

Cx601 on uusi harvinaislääkestatuksen saanut valmiste, joka on tarkoitettu Crohnin tautia sairastavilla esiintyvien vaikeahoitoisten perianaalisten fisteleiden hoitoon. Euroopan lääkevirasto (EMA) on ottanut tämän lääkkeen myyntilupa-arviointiin maaliskuussa 2016 faasin 3 tutkimuksen (ADMIRE-CD) tulosten perusteella. Tutkimuksessa Cx601-valmisteella hoidetuilla potilailla oli 44 % suurempi todennäköisyys saavuttaa hoitovaste verrattuna lumevalmisteeseen.

Tehdyn lisensointisopimuksen mukaisesti Takeda tulee olemaan tämän valmisteen myyntiluvan haltija ja vastaamaan tuoterekisteröintiin liittyvistä toimista ja kaupallistamisesta sovitulla markkina-alueella. Cx601-lääkkeen lisensointi Takedan tuotevalikoimaan lisää edelleen Takedan näkyvyyttä tulehduksellisten suolistosairauksien alueella, osoittaa Takedan vahvaa sitoutumista Crohn-potilaiden hoidon kehittämiseen ja vahvistaa samalla Takedan johtavaa asemaa gastrointestinaalialueen sairauksien lääkehoidossa.

 

Viitteet:

  1. Panés P, ym. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. The Lancet [online]. http://dx.doi.org/10.1016/S0140-6736(16)31203-X.
  2. Sands BE, Anderson FH, Bernstein CN, ym. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350: 876–85.
  3. Present DH, Rutgeerts P, Targan S, ym. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999; 340: 1398–405.

       FI/OTH/0816/0011

                       

 

 

 

Takeda and TiGenix Announce Publication in The Lancet of

24-Week Results of the Phase 3 ADMIRE-CD Trial Investigating Cx601 in the Treatment of Complex Perianal Fistulas in Patients with Crohn’s Disease

 

Osaka, Japan, August 2, 2016, and Leuven, Belgium, August 2, 2016 – Takeda Pharmaceutical Company Limited (TSE: 4502) (“Takeda”) and TiGenix NV (Euronext Brussels: TIG) (“TiGenix”) today announced that the 24-week results of the Phase 3 ADMIRE-CD trial investigating Cx601 have been published in The Lancet.1 Cx601 is a suspension of allogeneic adipose-derived stem cells (eASC) injected intra-lesionally for the treatment of complex perianal fistulas in patients with Crohn’s disease with an inadequate response to at least one conventional or biologic therapy.

 

The ADMIRE-CD trial is a randomized, double-blind, placebo-controlled, Phase 3 study, designed to investigate the efficacy and safety of a single treatment of Cx601 for the treatment of complex perianal fistulas in Crohn’s disease patients. A significantly greater proportion of patients in the Cx601 group versus the placebo group achieved the primary endpoint of combined remission (defined as clinical assessment of closure of all treated external openings draining at baseline, despite gentle finger compression, and absence of collections >2cm confirmed by MRI) at week 24 in the ITT population 53 (50%) of 107 vs 36 of 105 (34%), respectively (97.5% CI 0.2–30.3; p=0.024) and the mITT population 53 (51%) of 103 vs 36 (36%) of 101 (0.5–31.2; p=0.021). These results were confirmed in the per-protocol population and in additional supportive and sensitivity analyses. This definition of remission is more stringent than those commonly used in clinical trials on perianal fistulizing disease, as it includes both clinical and radiological assessment by MRI.2,3 Treatment-emergent adverse (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and placebo arms.

 

In addition, severity of perianal Crohn’s disease was assessed at baseline and all study visits with the Perianal Disease Activity Index (PDAI). In the mITT population, the PDAI score was similar in the Cx601 and the placebo groups at baseline. The improvement in PDAI with Cx601 was significantly greater than placebo at week 6, 12 and 18. In addition, the mean total PDAI score at week 24 with Cx601 (4.4) was close to the threshold for inactive perianal disease (PDAI<4) at which patients do not need medical or surgical treatment.

 

Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract that affects approximately five million patients worldwide.4 People living with Crohn’s disease often experience complex perianal fistulas for which there are limited treatment options. Recognizing the debilitating nature of the disorder and the lack of treatment options, in 2009 the European Commission granted Cx601 orphan designation for the treatment of complex perianal fistulas in Crohn’s disease. In March 2016, TiGenix announced that it submitted the Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Cx601. TiGenix also recently announced 52-week data5 indicating the potential for efficacy and safety of a single treatment of Cx601 are maintained during a year of follow up.

 

“We are very proud of the results of this study,” said Prof. Dr. Julián Panés, ADMIRE-CD Global Study Coordinator and Head of the Inflammatory Bowel Diseases Unit at the Hospital Clínic of Barcelona. “The Lancet is one of the most highly regarded and well known medical journals in the world; we are very delighted to have the Cx601 data selected by this prestigious publication,” he continued.

 

Dr. Marie Paule Richard, Chief Medical Officer at TiGenix stated that, “Our study is, to our knowledge, the first large-scale, randomized placebo-controlled, clinical trial to use clinical assessment of fistula closure and MRI assessment of absence of abscesses as recommended in the European Crohn’s and Colitis Organization guidelines.6”

 

Last month, TiGenix entered into a licensing agreement with Takeda, a global leader in gastroenterology, under which Takeda acquired the exclusive right to develop and commercialize Cx601 for complex perianal fistulas in Crohn’s disease outside the United States (U.S.). Based on the data from this pivotal Phase 3 trial in Europe, TiGenix submitted an MAA to the EMA in the first quarter of 2016, and a decision by the EMA could be expected in 2017. If granted, following Marketing Authorization in the European Economic Area Takeda will become the Marketing Authorization holder and will be responsible for all commercialization and regulatory activities.

 

A pivotal Phase 3 trial for Cx601 for the treatment of complex perianal fistulas is expected to start in the U. S. in 2017. In the U.S., TiGenix intends to apply for fast track designation from the U.S. Food and Drug Administration (FDA), which would facilitate and expedite the development and review process in the U.S.

 

About Takeda

Takeda Pharmaceutical Company Limited (TSE: 4502) is a global, R&D-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its research efforts on oncology, gastroenterology and central nervous system therapeutic areas. It also has specific development programs in specialty cardiovascular diseases as well as late-stage candidates for vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology, central nervous system and gastroenterology, as well as its presence in emerging markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

 

Takeda’s Commitment to Gastroenterology

Takeda is a global leader in gastroenterology. With expertise spanning more than 25 years, the company’s dedication to innovation continues to evolve and have a lasting impact. ENTYVIO® (vedolizumab) demonstrates Takeda’s global capabilities and expansion into the specialty care market in gastroenterology and biologics. Designed and developed specifically to target the gastrointestinal (GI) tract, ENTYVIO was launched in 2014 for the treatment of adults with moderate to severe ulcerative colitis and Crohn’s disease. TAKECAB® (vonoprazan fumarate) is Takeda's potassium-competitive acid blocker and was launched in Japan in 2015. Takeda also markets motility agent AMITIZA® (lubiprostone), which originally launched in 2006 for the treatment of chronic idiopathic constipation, and received subsequent approval to treat irritable bowel syndrome with constipation and opioid-induced constipation. Preceding these notable launches, Takeda pioneered gastroenterological breakthroughs in proton pump inhibitors beginning in the 1990’s with lansoprazole. Through specialized and strategic in-house development, external partnerships, in-licensing and acquisitions, Takeda currently has a number of promising early stage GI assets in development, and remains committed to delivering innovative, therapeutic options for patients with gastrointestinal and liver diseases.

 

About TiGenix

TiGenix NV (Euronext Brussels: TIG) is an advanced biopharmaceutical company focused on developing and commercialising novel therapeutics from its proprietary platforms of allogeneic, or donor-derived, expanded stem cells. Two products from the adipose-derived stem cell technology platform are currently in clinical development. Cx601 is in Phase III for the treatment of complex perianal fistulas in Crohn’s disease patients. Cx611 has completed a Phase I sepsis challenge trial and a Phase I/II trial in rheumatoid arthritis. Effective July 31, 2015, TiGenix acquired Coretherapix, whose lead cellular product, AlloCSC-01, is currently in a Phase II clinical trial in acute myocardial infarction (AMI). In addition, the second product candidate from the cardiac stem cell-based platform acquired from Coretherapix, AlloCSC-02, is being developed in a chronic indication. On July 4, 2016, we entered into a licensing agreement with Takeda, a large pharmaceutical company active in gastroenterology, under which Takeda acquired the exclusive right to commercialize Cx601 for complex perianal fistulas outside the United States. TiGenix is headquartered in Leuven (Belgium) and has operations in Madrid (Spain). For more information, please visit http://www.tigenix.com/.

 

About Cx601

Cx601 is a suspension of allogeneic expanded adipose-derived stem cells (eASC) locally injected. Cx601 is an investigational agent being developed for the treatment of complex perianal fistulas in Crohn’s disease patients that failed conventional therapy including antibiotics, immunosuppressant, or anti-TNF therapy. Crohn’s disease is a chronic inflammatory disease of the intestine and patients can suffer from complex perianal fistulas for which there is currently no effective treatment. In 2009, the European Commission granted Cx601 orphan designation for the treatment of anal fistulas, recognizing the debilitating nature of the disease and the lack of treatment options. Based on positive Phase 2 results, TiGenix sought scientific advice from the European Medicines Agency (EMA) on the future development path of Cx601. TiGenix then initiated a randomized, double-blind, placebo-controlled Phase 3 trial in Europe and Israel designed to comply with the requirements laid down by the EMA. ‘Madrid Network,’ an organization within the Autonomous Region of Madrid which helps companies to grow through high-technology innovation, issued a soft loan to help finance this Phase 3 study. The program is funded by The Secretary of State for Research, Development and Innovation (Ministry of Economy and Competitiveness) within the framework of the INNTEGRA plan. The study’s primary endpoint was combined remission, defined as clinical assessment at week 24 of closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections >2cm confirmed by MRI. In the 24 weeks results of the Phase 3 study reported in August 2015, Cx601 achieved statistically significant superiority (p<0.025) on the primary endpoint with 49.5% combined remission at week 24 compared to 34.3% in the placebo arm in the ITT population. These results translate into a relative risk of 1.44, meaning that patients receiving Cx601 had a 44% greater probability of achieving combined remission than placebo patients. Efficacy results were robust and consistent across all statistical populations. Treatment emergent adverse events (non-serious and serious) and discontinuations due to adverse events were comparable between Cx601 and placebo arms. The Phase 3 study trial has completed a follow-up analysis at 52 weeks post-treatment. Based on the positive 24 weeks Phase 3 study results, TiGenix has submitted a Marketing Authorization Application to the EMA in early 2016. TiGenix is preparing to develop Cx601 in the U.S. after having reached an agreement with the FDA through a special protocol assessment procedure (SPA) in 2015. On July 4, 2016 TiGenix entered into a licensing agreement with Takeda, a pharmaceutical company leader in gastroenterology, whereby Takeda acquired an exclusive right to commercialize Cx601 for complex perianal fistulas in Crohn’s patients outside of the U.S.

 

###

 

CONTACTS:

For TiGenix:

Claudia D'Augusta

Chief Financial Officer

claudia.daugusta@tigenix.com

+34 91 804 92 64

 

For Takeda:

Tsuyoshi Tada

Media in Japan

tsuyoshi.tada@takeda.com

+81 33 278 2417

 

Elissa Johnsen

Media outside of Japan

elissa.johnsen@takeda.com

+1 224 554 3185

 

References 

1. Panés
P, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. The Lancet [online]. Last accessed July 289, 2016, available at

http://dx.doi.org/10.1016/S0140-6736(16)31203-X.

2. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350: 876–85.

3. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999; 340: 1398–405.

4. World IBD Day. Home. Last accessed July 29, 2016, available at http://www.worldibdday.org/index.html.

5. TiGenix Press Release. TiGenix announces positive 52-week Phase III results of Cx601 in complex perianal fistulas in Crohn’s disease patients. Last accessed July 29, 2016, available at

http://bit.ly/2aA7DJr.

6. Van Assche G, Dignass A, Reinisch W, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: special situations. J Crohns Colitis 2010; 4: 63–101.

Tietoja Takedasta:

Takeda Oy on Japanin Osakassa pääkonttoriaan pitävän Takeda-konsernin suomalainen markkinointi- ja myyntiorgani-saatio, jonka toimitilat sijaitsevat Helsingissä.

Takeda on tutkimukseen keskittyvä maailmanlaajuinen yritys, jonka toiminta painottuu lääkealalle. Takeda on Japanin suurin lääkeyritys ja yksi alan suurista toimijoista maailmanlaajuisesti, ja se on sitoutunut tavoittelemaan parempaa elämänlaatua johtavilla lääkeinnovaatioilla. Takeda on muuttanut itseään strategisilla yritysostoilla ja laajentanut sekä terapeuttista asiantuntemustaan että maantieteellistä ulottuvuuttaan. Takeda toimii yli 70 maassa, ja sillä on erityisen vahva asema Aasiassa, Pohjois-Amerikassa, Euroopassa ja nopeasti kasvavilla markkina-alueilla, kuten Latinalaisessa Amerikassa, Venäjällä ja entisissä Neuvostoliiton maissa sekä Kiinassa. Toiminnan painopistealueita ovat gastroenterologia, onkologia, keskushermostosairaudet, sydän- ja verisuonisairaudet sekä rokotteet.

Lisätietoja Takeda Oy:stä yrityksen verkkosivuilla www.takeda.fi.                                        

 

 

 

 

 

 

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