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GLPG0634 (Filgotinib)

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pe26
2
quote:

Krustie101 schreef op 7 juni 2020 12:02:


Alhoewel Abbvie de aanbeveling tot goedkeuring in Japan niet aangregepen heeft om een PB uit te brengen, heeft het dit wel gedaan voor de CHMP opinion (de finale goedkeuring is 67 dagen later)

news.abbvie.com/news/press-releases/a...

Misschien dat we van Gilead eind juni of eind juli hetzelfde mogen verwachten. Hier kan je het zelf volgen

www.ema.europa.eu/en/committees/chmp/...

Op het einde van de maand kan je hier de agenda raadplegen om te kijken of Filgotinib voor een opinion geagendeerd is (rubriek 3.1, verleden maand stond het daar verkeerd onder). Na de CHMP meeting kan je al snel in de highlights het resultaat terug vinden.




Aanbevolen!!

15 augustus 2019: EUROPEAN MEDICINES AGENCY VALIDATES MARKETING APPLICATION FOR FILGOTINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

Haal daar de 67-61 dagen vanaf, Abbvie persbericht 18 oktober 2019 CHMP positive opinion en 18 december 2019 goedkeuring, en dan.....

Aftellen naar het CHMP oordeel Filgotinib (ontwikkeld door Galapagos) tussen morgen en 15 juni 2020!!
Krustie101
3
quote:

Woman in Chains32 schreef op 7 juni 2020 12:14:


[...]


Aanbevolen!!

15 augustus 2019: EUROPEAN MEDICINES AGENCY VALIDATES MARKETING APPLICATION FOR FILGOTINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

Haal daar de 67-61 dagen vanaf, Abbvie persbericht 18 oktober 2019 CHMP positive opinion en 18 december 2019 goedkeuring, en dan.....

Aftellen naar het CHMP oordeel Filgotinib (ontwikkeld door Galapagos) tussen morgen en 15 juni 2020!!


We zullen iets meer geduld moeten hebben. De volgende meeting is gepland van 22 tot 25 juni:

www.ema.europa.eu/en/documents/other/...

Het moet dan ook nog onder rubriek 3.1 op de agenda staan.
pe26
2
Ik redeneer de verkeerde kant om (wake-up call) door te refereren naar concurrente timelines.

Goed van je verduidelijkingen.

Ik houd me vanaf nu vast aan agenda CHMP 22-25 juni.
Roel76
0
quote:

Woman in Chains32 schreef op 4 juni 2020 11:26:


Graag even meedenken. Een Sanderus kan dit bijvoorbeeld goed duiden hoop ik.


Japan filing. Daar gaat hij mij om in relatie tot Filgotinib.


Filing upadacitinib voor FDA en EMA d.d. 20 december 2018.

Een J-NDA filing gebeurt dikwijls 1-2 maanden later dan FDA/EMA filing wegens vertaling en andere standaarden.
Wat valt er te lezen over J-NDA filing upadacitinib voor Japan.

(1) AbbVie said on February 26 (2019) that it has submitted a new drug application in Japan for its oral selective JAK inhibitor upadacitinib for the treatment of moderate to severe rheumatoid arthritis (RA) in adults.The filing is based on five of.......
pj.jiho.jp/article/239516

(2) MHLW Panel OKs Bayer’s Xtandi Rival, AbbVie’s JAK Inhibitor: a key health ministry advisory committee (m.i. MHLW) on November 25 2019 gave its thumbs-up for an array of new medicines for approval, including Bayer Yakuhin’s prostate cancer drug darolutamide and AbbVie’s oral selective JAK inhibitor upadacitinib for the treatment of rheumatoid arthritis…
pj.jiho.jp/article/241096

Conclusie: eind februari > eind november = 9 maanden.

De standaard procedure Japan voor goedkeuring is wat ik lees 12 maanden; vergelijkbaar met FDA/EMA.
Bij FDA loopt de priority review voor Filgotinib, waardoor 4 maanden tijdswinst wordt voorzien.
Orphan drug status traject Japan duurt 9 maanden o.b.v. onderstaande link.
www.pharmasug.org/proceedings/2015/SS...


Wanneer gaat Filgotinib goedgekeurd worden in Japan..?

> 9 oktober 2019 J-NDA filing Filgotinib door Gilead voor Japan
+ 9 maanden...
> 9 juli 2020 bij succesvolle procedure is goedkeuring voor Filgotinib in Japan behoort dus een reële mogelijkheid. Over 1 maand!

Filgotinib is veiliger dan upadacitinib; dat is ook gebleken uit Japanese RA studie-data van upadacitinib.
Waarom zou het voor Filgotinib anders zijn dan voor upadacitinib.


Iemand...?


Op het andere forum heeft Sanderus dit geantwoord, omdat jullie beiden de specialisten zijn toch interessant denk ik.

“Met mijn allergrootste respect voor WIC32 maar de opinie voor filgotinib in Japan verwacht ik niet in juli maar ten vroegste in q4.
Het dossier werd door Gilead ingediend begin oktober 2019.

In addition to the 1 year standard approval review time of the MHLW for approval of new
drugs from April 1, 2000 (dated March 28, 2000) (excluding the time taken by applicants to
prepare responses, etc.), the time allotted to the applicant is also 1 year so that the time from
the application to marketing approval is a maximum of 2 years

Wat de opinie van de CHMP betreft in de EU kan dit deze maand komen maar het kan juli ook worden.

Lees meer op: beursig.com/forum/viewtopic.php?f=4&a... voor meer informatie“

Hopelijk voegt dit nog iets toe aan de discussie

Groeten Roel
pe26
5
quote:

Roel76 schreef op 10 juni 2020 16:00:


[...]

Op het andere forum heeft Sanderus dit geantwoord, omdat jullie beiden de specialisten zijn toch interessant denk ik.

“Met mijn allergrootste respect voor WIC32 maar de opinie voor filgotinib in Japan verwacht ik niet in juli maar ten vroegste in q4.
Het dossier werd door Gilead ingediend begin oktober 2019.

In addition to the 1 year standard approval review time of the MHLW for approval of new
drugs from April 1, 2000 (dated March 28, 2000) (excluding the time taken by applicants to
prepare responses, etc.), the time allotted to the applicant is also 1 year so that the time from
the application to marketing approval is a maximum of 2 years

Wat de opinie van de CHMP betreft in de EU kan dit deze maand komen maar het kan juli ook worden.

Lees meer op: beursig.com/forum/viewtopic.php?f=4&a... voor meer informatie“

Hopelijk voegt dit nog iets toe aan de discussie

Groeten Roel




Dank Roel, de definitieve goedkeuring van het MHLW zal inderdaad in september/oktober komen.

Echter bestaat er een gerede kans dat adviescommissie MHLW, genoemd panel, wel binnen 9 maanden na indiening J-NDA een waarde-oordeel afgeeft.

Bij RINVOQ (upadacitinib) kwam het goedkeurende oordeel van panel MHLW binnen 9 maanden.
2 maanden later werd het definitief goedgekeurd. Dat heeft Krustie reeds beschreven.

Tijdschema (JMHO)
9 oktober 2019: indiening J-NDA filgotinib >>> 9 maanden later.
9 juli 2020: goedkeurende oordeel omtrent J-NDA filgotinib door MHLW-panel
sept.okt. 2020: definitieve goedkeuring MHLW.

Ik houd voorlopig vast dat we binnen paar weken daar meer over horen.
Pharma Japan zal het tonen.
pj.jiho.jp/genre/regulatory
Krustie101
0
De PB's van Abbvie in verband met de goedkeuring van Rinvoq in Japan bevestigen de tijdslijn die WiC23 had gevonden op Pharma Japan. Ze zijn niet terug te vinden op Abbvie Global, wel op Abbvie Japan

Voorgelegd op 26 februari 2019
www.abbvie.co.jp/our-company/press-re...

Goedgekeurd op 23 januari 2020
www.abbvie.co.jp/our-company/press-re...
abelheira
1
Verschil aanvraag - goedkeuring : 11 maanden.
Goedkeuring in Japan bijgevolg begin september?
pe26
0
ja, klopt abelheira. En in 9 maanden zou je voorlopig oordeel van MHLW mogen verwachten.

www.gilead.com/-/media/files/pdfs/oth...


Bovenstaande incentive is afgerond.
Gilead/Galapagos hebben veel belang bij verdere uitdieping JAK//STAT.
Wie weet zijn de pilots nog van pas gekomen voor review gesprekken van regelgevende instanties.
avantiavanti
13
Jon Goldhill, Pharma Information and Reports LTD, UpdatesPlus/LeadDiscovery June 19 2020

EULAR 2020: New data presented from the FINCH program including 52wk results and an integrated safety analysis
Bijlage:
El buitre
3
quote:

avantiavanti schreef op 19 juni 2020 11:10:


Jon Goldhill, Pharma Information and Reports LTD, UpdatesPlus/LeadDiscovery June 19 2020

EULAR 2020: New data presented from the FINCH program including 52wk results and an integrated safety analysis



Spijker op zijn kop: “.. Rinvoq produced a clear dose response on serious infection and zoster, and this is reflected in the approval of just the 15mg dose. In contrast there is not a clear dose response for filgotinib supporting approval of both doses and possibly an argument for differing MOAs which could feed into the discussion around not including VTE as a risk”
Wall Street Trader
4
JAKs could offer convenience advantages over other biologics

As a once-daily oral treatment, JAK inhibitors offer potential convenience advantages
over competitor biologics which often require physician visits for intravenous
administration. A subcutaneous formulation of Entyvio for maintenance
treatment has been filed with regulators, with US FDA issuing a Complete Response
Letter in December but European approval likely after a positive CHMP decision.

As small molecules, an added advantage of JAK inhibitors is the lack of anti-drug
antibodies, which may increase the likelihood of sustained responses, versus the loss
of response which can occur with biologics, as well as enabling intermittent treatment
for disease flares, which is generally not advisable for biologics.

Safety in focus

Safety will be a key focus for the SELECTION trial, given the concerns related to the
JAK inhibitor class overall, but could potentially act as confirmation of filgotinib's
differentiated safety profile. In July 2019 FDA issued new warnings about an
increased risk of blood clots and death with the 10mg twice daily (bid) dose of Xeljanz,
and recommended reserving use for patients who have failed or are intolerant of antiTNFs,
avoiding use in patients at high risk of thrombosis and limiting the use of the 10mg
bid dosage to the shortest duration needed. Europe's EMA followed suit in November
2019, advising that Xeljanz should be used with caution in patients at high risk of blood
clots and limiting use in patients >65 years.

Potentially differentiated safety profile

Other JAK inhibitors have been shown to produce a range of side effects, including
abnormalities in platelets, low density lipoprotein (LDL), cholesterol, red blood cell count
and NK (natural killer) cell count, raising concerns about risk of serious infections and
venous thromboembolism (VTE). Filgotinib has more JAK1 selectivity than
any other JAK inhibitor, which could result in an improved safety profile.

In keeping with this, the Phase II DARWIN and Phase III FINCH RA programmes
confirmed filgotinib's potentially best-in-class safety profile with
rates of VTE, serious infection, opportunistic infection, malignancy, major adverse
cardiovascular events and death broadly in-line or below placebo rates.

An added potential benefit of filgotinib for inflammatory bowel disease (IBD) is the
lack of adverse effect
on haemoglobin levels demonstrated in trials to-date, with an
actual increase in levels of up to 4% in the DARWIN trial. This compares favourably
to Xeljanz, which carries a warning requiring haemoglobin monitoring and doseadjustment
depending on levels. This is particularly important for IBD, with up to
one-third of patients suffering from recurrent anaemia, and could potentially be a
differentiating factor for filgotinib.

MANTA studies ongoing

FDA has previously had issues regarding use of the highest 200mg/day filgotinib
dose in male patients, based on concerns over toxicity to the male reproductive system
relating to rat/dog toxicology studies. Consequently, despite the fact the Phase II
DARWIN trials confirmed no clinically meaningful changes in male hormone levels, US
males taking part in the Phase III SELECTION UC and Phase III DIVERSITY Crohn's
disease studies are only eligible to receive the higher 200mg/day dose if they have failed
at least one prior biologic.

In contrast, the FINCH RA programme, approved by a different FDA division, allowed
inclusion of the 200mg/day dose, but included a dedicated male UC patient testicular
safety study, MANTA, which could finally lay safety concerns to rest. During
2019, a second study, MANTA-RAy was initiated, with more relaxed inclusion criteria
and including patients with other rheumatic diseases, in order to speed up recruitment,
albeit enrolment into both studies has now been paused due to the COVID-19 outbreak.
Unblinded data from these male safety studies will be made available to FDA as part of
the RA filing.

Broad applicability means multi-blockbuster potential

It remains unclear when Gilead/Galapagos will share the topline MANTA data, given Gilead expects patient recruitment to finish in "H2:20". Initially assumed the partners would unblind the
data in 2020 to support the RA filing (PDUFA expected in Aug 2020), but Galapagos has recently said MANTA is not required for approval, and that the company would share the data in an
unblinded manner.

galaking
0
Ik kom nu filgonitib helemaal niet meer tegen in de agenda voor het CHMP deze week. Ik begrijp er even niets meer van.
Galafilgo
0
quote:

galaking schreef op 23 juni 2020 18:27:


Ik kom nu filgonitib helemaal niet meer tegen in de agenda voor het CHMP deze week. Ik begrijp er even niets meer van.


vind je het gek dat de koers daalt?
allemaal onzekerheid
lmr
16
Voor zover bekend, niet eerder langs zien komen:
Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation
Yang-Hui Jimmy Yeh,1 Katharine M. Jenike,2 Rachela M. Calvi,3 Jennifer Chiarella,3 Rebecca Hoh,4 Steven G. Deeks,4 and Ya-Chi Ho1
First published June 23, 2020

Poster: dm5migu4zj3pb.cloudfront.net/manuscri...

Despite effective antiretroviral therapy, HIV-1-nfected cells continue to produce viral antigens and induce chronic immune exhaustion. We propose to identify HIV-1-suppressing agents which can inhibit HIV-1 reactivation and reduce HIV-1-induced immune activation. Using a novel dual reporter system and a high-throughput drug screen, we identified FDA-approved drugs which can suppress HIV-1 reactivation in both cell line models and CD4+ T cells from virally suppressed, HIV-1-infected individuals. We identified 11 cellular pathways required for HIV-1 reactivation as druggable targets. Using differential expression analysis, gene set enrichment analysis and exon-intron landscape analysis, we examined the impact of drug treatment on the cellular environment at a genome-wide level. We identified a new function of a JAK inhibitor filgotinib which suppresses HIV-1 splicing. First, filgotinib preferentially suppresses spliced HIV-1 RNA transcription. Second, filgotinib suppresses HIV-1-driven aberrant cancer-related gene expression at the integration site. Third, we found that filgotinib suppresses HIV-1 transcription by inhibiting T cell activation and by modulating RNA splicing. Finally, we found that filgotinib treatment reduces the proliferation of HIV-1-infected cells. Overall, the combination of a drug screen and transcriptome analysis provides systemic understanding of cellular targets required for HIV-1 reactivation and drug candidates that may reduce HIV-1-related immune activation.

Full pdf: dm5migu4zj3pb.cloudfront.net/manuscri...

Source: www.jci.org/articles/view/137371#vers...
Piddybull.
0
imr ,
ik heb het integraal gekopieerd op het andere forum.
Volgende keer alle eer aan u daar ?
lmr
2
Hier nog wat extra informatie over de studie.
www.croiconference.org/abstract/a-jak...
De poster is al in begin maart voor het eerst gepitched en lijkt nu pas gepubliceerd te worden.

Conclusion:
Overall, a combination of drug screening and transcriptome analysis identified the landscape of cellular pathways critical for HIV-1 reactivation and a novel HIV-1-suppressing agent filgotinib. Filgotinib suppresses HIV-1 transcription and reducing the proliferation of HIV-1-infected cells by targeting two different pathways, involving inhibition of T cell activation and modulation of HIV-1-splicing. Therapeutic strategies targeting a combination of these pathways with increased selectivity against HIV-1-infected cells provides a new direction to reduce HIV-1-related immune activation and the expansion of the HIV-1-infected cells.

Acknowledgement:
We thank all study participants. We thank NIH AIDS Reagents Program. This work is supported by Yale Top Scholar, Rudolf J. Anderson Fellowship, American Foundation for AIDS Research (amfAR), NIH R01 AI141009, R61 DA047037, R21AI118402, W. W. Smith AIDS Research Grant, Johns Hopkins Center for AIDS Research Award P30AI094189, Gilead AIDS Research Grant (Y.-C.H.), Gilead HIV Research Scholar Grant, NIH BEAT-HIV Delaney Collaboratory UM1AI126620 and NIH CHEETAH P50 AI150464-13.
Lingus
0
quote:

lmr schreef op 23 juni 2020 19:33:


Voor zover bekend, niet eerder langs zien komen:
Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation
Yang-Hui Jimmy Yeh,1 Katharine M. Jenike,2 Rachela M. Calvi,3 Jennifer Chiarella,3 Rebecca Hoh,4 Steven G. Deeks,4 and Ya-Chi Ho1
First published June 23, 2020

Poster: dm5migu4zj3pb.cloudfront.net/manuscri...

Despite effective antiretroviral therapy, HIV-1-nfected cells continue to produce viral antigens and induce chronic immune exhaustion. We propose to identify HIV-1-suppressing agents which can inhibit HIV-1 reactivation and reduce HIV-1-induced immune activation. Using a novel dual reporter system and a high-throughput drug screen, we identified FDA-approved drugs which can suppress HIV-1 reactivation in both cell line models and CD4+ T cells from virally suppressed, HIV-1-infected individuals. We identified 11 cellular pathways required for HIV-1 reactivation as druggable targets. Using differential expression analysis, gene set enrichment analysis and exon-intron landscape analysis, we examined the impact of drug treatment on the cellular environment at a genome-wide level. We identified a new function of a JAK inhibitor filgotinib which suppresses HIV-1 splicing. First, filgotinib preferentially suppresses spliced HIV-1 RNA transcription. Second, filgotinib suppresses HIV-1-driven aberrant cancer-related gene expression at the integration site. Third, we found that filgotinib suppresses HIV-1 transcription by inhibiting T cell activation and by modulating RNA splicing. Finally, we found that filgotinib treatment reduces the proliferation of HIV-1-infected cells. Overall, the combination of a drug screen and transcriptome analysis provides systemic understanding of cellular targets required for HIV-1 reactivation and drug candidates that may reduce HIV-1-related immune activation.

Full pdf: dm5migu4zj3pb.cloudfront.net/manuscri...

Source: www.jci.org/articles/view/137371#vers...

Verrassende bonus-indicatie voor filgotinib. Preklinisch, maar positief. Of de werking in HIV bruikbaar en onderscheidend gaat zijn moet uit verder onderzoek blijken.
Lama Daila
8
Ik heb gewoon de onderzoeker zelf gevraagd of dit opportuniteiten biedt voor filgotinib in HIV:
twitter.com/lama_daila/status/1275640...

Benieuwd of er een antwoord volgt.
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