Galapagos yesterday trumpeted the start of eagerly awaited trials of its triplet candidates for cystic fibrosis. But the timing of the company’s update could be seen an attempt to gain an edge over its rival Vertex before the JP Morgan healthcare conference next week.
Vertex, which will present at the meeting on Monday morning, is due to start phase III trials of its own triplets in the first half of this year, and attendees will no doubt be looking for hints about which of its next-generation correctors it will move forward.
Vertex head start
The company, which could have a triplet approved as early as 2020, is thought to be around two years ahead of Galapagos and its partner Abbvie.
Vertex already has the backbone of its triplet in place with its marketed potentiator Kalydeco and a corrector, tezacaftor, so just needs to find a second corrector – it currently has four potential candidates, and is expected to take one or two triplet regimens into pivotal trials (Vertex eyes the treble in cystic fibrosis, July 19, 2017).
In the meantime, the US FDA is due to make an approval decision on tezacaftor in combination with ivacaftor – the active ingredient of Kalydeco – by February 28. The combo offers safety advantages over Vertex’s older doublet, Orkambi, and is expected to help the company capture a greater share of the cystic fibrosis market.
JP Morgan delegates will also hope for updated financial guidance from Vertex; however, this could be delayed until the FDA has made its decision on the new doublet.
Leerink analysts believe that the company’s cystic fibrosis franchise could bring in over $9bn by 2023 if all goes smoothly. However, one stumbling block could be getting payers on board with tezacaftor plus ivacaftor or a potential triplet, particularly in Europe.
Galapagos plays catch-up
Galapagos still has a lot of work to do to become a serious competitor to Vertex, but this did not stop the Belgian company’s share price climbing 5% today after yesterday’s post-market announcement.
The focus of the update was topline data from the phase II Flamingo trial of the group’s C1 corrector GLPG2222, given as monotherapy in patients homozygous for the F508del mutation.
GLPG2222 was found to decrease sweat chloride levels, with Galapagos claiming a dose response on this measure at day 29, something that was far from clear cut. Groups A-D represented ascending doses, the company told EP Vantage, but the best response was seen in the third of four dosing groups; this was also the only dose to reduce sweat chloride significantly versus placebo.
|Flamingo (NCT03119649) trial sweat chloride results|
|Placebo (n=11)||Dose A (n=10)||Dose B (n=10)||Dose C (n=14)||Dose D (n=14)|
|Mean change day 15 vs baseline (mmol/l)||-5.0||-9.6||-7.7||-16.2*||-12.5|
|Mean change day 29 vs baseline (mmol/l)||-2.5||-5.8||-6.6||-18.3*||-8.8|
|*p<0.05; Source: Company press release.|
There was no improvement in percent predicted forced expiratory volume in one second, ppFEV1, a measure of lung function, making the results look similar to those from the Albatross trial of GLPG2222 in combination with Kalydeco (Galapagos goes for broke in cystic fibrosis, November 21, 2017). That study was in a different population: patients with one F508del mutation and one gating mutation.
A better test of Galapagos’s competitive potential could come with the readout of the phase II Pelican study in the first half of the year. This is testing its C2 corrector, GLPG2737, plus Orkambi – lumacaftor plus ivacaftor – in homozygous F508del patients.
However, with Vertex already moving from lumacaftor to tezacaftor with its triplet strategy, a win here might not help Galapagos gain ground.
Triplets are coming
Galapagos hopes to develop an in-house triplet, and appears to be making some progress, yesterday saying it would begin dosing in a study of GLPG2451, GLPG2222 and GLPG2737 this quarter. Although this is a delay from a previous estimate of late 2017, initial data are still expected mid-year.
However, there are concerns about tissue accumulation with the potentiator GLPG2451, shifting hopes to Galapagos’s next contender, made up of GLPG3067/2222/2737, which recently started a trial in healthy volunteers.
And there are still questions about the company’s US strategy; the aforementioned triplet trials will be carried out in Europe.
Other cystic fibrosis rivals, including ProQR and Proteostasis, are also well behind Vertex. The latter has completed a healthy volunteer study of its triplet, comprising PTI-428 (amplifier), PTI-801 (corrector) and PTI-808 (potentiator), and hopes to begin a study in cystic fibrosis patients this year.
Meanwhile, ProQR has an inhaled antisense RNA project, QR-010, which could address the underlying cause of cystic fibrosis. The group reported positive phase Ib data in September in homozygous F508del patients and plans to start a phase II trial this year.
For now, Vertex is in the driving seat in cystic fibrosis – but its rivals will no doubt be looking out for signs of any chinks in its armour at JP Morgan next week.
|Selected Galapagos cystic fibrosis projects|
|GLPG2222||C1 corrector||Phase II||NCT03045523 (Albatross)||F508del/gating mutation||2222 + Kalydeco||Reported|
|NCT03119649 (Flamingo)||F508del homozygous||Monotherapy||Reported|
|GLPG2737||C2 corrector||Phase II||2017-002181-42 (Pelican)||F508del homozygous||2737 + Orkambi vs Orkambi alone||H1 2018|
|GLPG2851||C1 corrector||Phase I||-||Healthy volunteers||Unknown||Future medical conference|
|GLPG2451/2222/2737||Triple therapy||Phase I||-||Hetero and homozygous patients||Unknown||Summer 2018|
|GLPG3067/2222/2737||Triple therapy||Phase I||-||Healthy volunteers||Multiple ascending doses||H1 2018|
|GLPG3067/2222/3221||Triple therapy||Phase I||To start 2018||Unknown||Unknown||Unknown|
|Source: Company press release.|
This story has been updated to reflect comments from Galapagos.
To contact the writer of this story email Madeleine Armstrong in London at firstname.lastname@example.org. For live updates from the JP Morgan healthcare conference in San Francisco on January 8-11 follow @ByMadeleineA on Twitter.
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