Aandeel Galapagos AEX:GLPG.NL, BE0003818359

quote:

aston.martin schreef op 25 oktober 2017 21:08:

[...]

Ik durf ook niet echt met zekerheid conclussies te trekken uit deze verlengde studie. Toch kan ik mij moeilijk voorstellen dat er toestemming gegeven wordt voor deze extra 3 jaren als de patiënten niet gebaat zouden zijn met de behandeling. Nu zeker niet, gezien het stopzetten van de mongersen-studie vorige week wegens gebrek aan werkzaamheid. Bovendien verwacht men dat ca 80% van de patiënten zal doorgaan met de behandeling.
Ik ben bijgevolg toch eerder geneigd om te zeggen dat filgotinib een goede werkzaamheid heeft en dat men de veiligheid op lange termein wil onderzoeken.

quote:

pe26 schreef op 25 oktober 2017 22:29:

CTP-656 = nu VX-561.

2 triples door Vertex gestart met VX-561 als once daily potentiator binnen 4-weeks behandeling.
Begin 2018 weten we meer.

Morgen de beurt aan Galapagos om nieuws te brengen omtrent vorderingen CF-programma.

Eindelijk de radiostilte voorbij.

quote:

NielsjeB schreef op 25 oktober 2017 21:36:

Abbvie’s Jak flashes a warning for the whole class - $GLPG $GILD $ABBV
Kan iemand bij dit artikel? t.co/mRPQ5tbVHx

quote:

Zuiderbuur schreef op 26 oktober 2017 17:41:

[...]
Via een andere bron - www.epvantage.com/Universal/View.aspx...
(de tabellen krijg ik hier niet leesbaar geplaatst)

Abbvie’s Jak flashes a warning for the whole class

Date October 25, 2017

Just when Lilly determined to press ahead with its Jak inhibitor Olumiant, more fears have emerged that most of the class could be doomed in its biggest use, rheumatoid arthritis.

The concerns came yesterday from updated findings with Abbvie’s Jak competitor upadacitinib, suggesting that the risk of thrombotic events is even greater than feared. The fallout could also hit Gilead’s filgotinib and, with the sellside expecting upadacitinib and Olumiant to play important roles in RA, differently acting injectables could be the obvious beneficiaries (see tables below).

Indeed, sellside consensus data from EvaluatePharma suggest that, of the assets currently in development, upadacitinib will in 2022 represent the biggest-selling RA drug. With expected 2022 revenue of $574m in RA Olumiant appears eleventh overall.

Top 10 rheumatoid arthritis products in 2022 (tabel)

The Lilly drug is approved in the EU, but has been knocked back with a US complete response letter. On yesterday’s third-quarter earnings call Lilly said it was accumulating data for resubmitting the asset; as for thromboembolic events specifically, it said real-world evidence pointed to this adverse event being consistent with “background rates in the RA patient population”.

Late-breaking shocker

All does not seem to be business as usual, however, judging by late-breaking abstracts for next month’s American College of Rheumatology meeting, which went live this week.

Among these appeared 12-week extension data in upadacitinib’s Select-Beyond trial. Most worrying was the disclosure of four new venous thromboembolic events (VTEs), coming on top of the two that had earlier sounded the first note of caution over the Jak class (Therapy focus – Atopic dermatitis competition Jaks up, September 14, 2017).

Leerink analysts painted a bleak picture, suggesting that it was no longer possible to dismiss this as background noise. The phase III VTE rate is now 16.3 per 1,000 patient years of exposure, well above the 3-8 rate expected for RA, they wrote, calling this “a clear signal about [upadacitinib’s] pro-thrombotic activity”.

Of course, it is not clear to what extent Olumiant would be hit, but the Abbvie data should lead to further scrutiny. Lilly has said that it will resubmit Olumiant by the end of January 2018; the FDA previously asked the company to look into the observed imbalance in VTEs during the placebo-controlled period of its RA clinical trials.

Leerink reckons that if upadacitinib does have a VTE signal, and if Olumiant is delayed further for the same reason, then “it is hard to imagine Gilead’s filgotinib [being] spared from heightened scrutiny, and possibly even class labelling as well”. This class includes other assets from Astellas, Pfizer, Concert and Aclaris.

What's at stake: the Jak inhibitor pipeline (tabel)

Of this quartet only Astellas’s ASP015K seems to be in trials for RA, however. RA is the most advanced and currently biggest forecast indication for upadacitinib and Olumiant, though this could change given the impressive phase II data the former generated in atopic dermatitis last month.

If there is a silver lining it is that Xeljanz, Pfizer’s marketed Jak inhibitor, seems not to be associated with VTEs, judging by Leerink’s exhaustive review of post-marketing data, and a separate American College of Rheumatology late-breaker looking across phase II and III trials in RA, psoriasis, psoriatic arthritis and ulcerative colitis.

Still, while it cannot be said for sure that this is a class effect, increased monitoring could lead to more VTEs being found, given their frequently asymptomatic nature. Abbvie has shown that this problem is now too widespread to ignore.

quote:

Sparrow2 schreef op 26 oktober 2017 18:52:

Hier is de link naar de allereerste waarschuwing in september over AbbVie en hun Thrombotic Event.

www.biopharmadive.com/news/abbvie-kee...

quote:

NielsjeB schreef op 26 oktober 2017 19:43:

Dankjewel Zuiderbuur. We zijn inmiddels dus niet de enigen die ABT-494's safety profile maar zozo vinden. Leerink heeft wel een punt mbt de JAK, de toezichthouder zal hier met argusogen naar kijken. Zolang filgotinib op het huidige safety-niveau blijft (laatste ACR-abstract [1] wijst zelfs op verdere verbetering sinds vorige LTE data [2]), wordt dit een van de belangrijkste onderscheidende eigenschappen. Precies zoals voorspeld en verwacht door Galapagos.

LTE data die tijdens de ACR gepresenteerd gaat worden is 168 weken (tijdens EULAR 144). Patient year exposure (PYE) van 1314 naar 1708.

Week 84 (van LTE):
Based on ‘observed case’ analysis, 86%, 69%, and 47% of 560 subjects achieved ACR20/50/70, respectively, and 71% (386/543) achieved DAS28-CRP <=3.2.

Week 60 (van LTE):
Based on an observed case analysis 84% (505/601), 65% (389/601), 44% (267/601) and 51% (299/587) of patients reached ACR20, ACR50, ACR70 and DAS28(CRP) remission at Week 60 respectively.

Vooral DAS28 change is opvallend (51% naar 71%). Geeft ook een belangrijk signaal dat de patient zichzelf ook daadwerkelijk beter voelt (gedeeltelijk subjectief dus).

Safety signals grotendeels verbeterd, alleen iets meer Serious TEAEs/100PYE (5.3 naar 5.6).
Aanrader om beide papers te vergelijken, zeker de laatste van ABT-494 en filgotinib.

[1] acrabstracts.org/abstract/long-term-s...
[2] ard.bmj.com/content/76/Suppl_2/267.1

quote:

BeursBonobo schreef op 26 oktober 2017 20:26:

?Nicola Finlay? aan Rheumatoid Arthritis Forum
4 uur ·
Week 12 Clinical Trial : Filgotinib
www.glpg.com/filgotinib

Today was my week 12 check up on study, I have been taking the study medication (either placebo, 100mg or 200mg) daily along with my usual meds (hydroxychloroquine 2 x 200mg, folic acid 5mg, prednisolone 2.5mg and omeprazole 20mg) and a weekly injection of 25mg/0.4ml MTX.

I had my bloods, urine, weight (remained stable and actually down 0.5Kg since I started- yay!), blood pressure, O2 sats and ECG done. I also answered a myriad of questions about my general health, daily activities, pain levels, exercise and general capabilities. Also any adverse effects, of which there are none and any illness. I somehow managed to pick up a UTI and a cold in the last three weeks……I hasten to say I am fine now and got over both in normal time.
My joint count is down to tenderness 1 (stupid pinkie isn’t getting with the programme) and swelling/puffiness 5. My wrists now look like normal human wrists and I have no pain. For those who don’t know before I started this clinical trial I was hospitalised in April for a week and after a brief period of respite due to steroid injections, was on crutches and could barely look after myself.

So I think it’s safe to say I am not on the placebo lol!
I then regaled my Rheumy and research nurse with my tale of a mountain walk I did a few weeks ago up Ben Vrackie (841meters/ 2759 feet) I suspect they were impressed about my improvement and new found zest for life.

Then the interesting part, my Rheumy said that the arms of this study that are aimed at people who have been on multiple drugs are easy to fill, although they do get a lot of dropouts at screening, because we are so desperate for help. The part they have difficulty with are the newly diagnosed. This could be down to information overload, denial of diagnosis or just fear of the unknown. All of which are good reasons.

But then I thought, why would you not want to try out a new drug, you skip trying several of the older drugs, maybe don’t need to take such a cocktail of drugs (like mine) and could possibly save yourself a lot of pain, discomfort, possible deformity and possibly even despair.

Now comes the guilt trip bit ?? Without people taking part in clinical trials like Kris and myself new drugs won’t get approval and we all could suffer longer.

So please if you are newly diagnosed consider taking part in a trial, it may work, it may not but that’s the same for any of the drugs they give us. Also fabulous one to one health care and free meds for the duration……..just saying!
Take care everyone. x