GLPG2451 for Cystic Fibrosis

Galapagos is aggressively pursuing drugs for people living with cystic fibrosis.  We previously wrote about Galapagos extensively here Galapagos.  Their previous top candidate, potentiator GLPG1837, has now been put on hold for a much more convenient once daily dosed potentiator GLPG2451.  The drug has completed the safety phase 1 clinical trial in healthy subjects, and by Galapagos standards was viewed as ready for a phase 1 combo trial with their lead corrector GLPG2222.  The ultimate goal for the company is to develop a triple combination for people with the F508del mutation, which represents around 90% of the total CF population.  The phase 1 and 2 clinical trials are being funded almost 100% by their partner AbbVie.  If this phase 1 combo clinical trial passes the safety test, then a third component corrector GLPG2737, which is currently in the safety phase of testing, will then be added to the combo 2451 and 2222 to form the triple.  The big picture goal is to produce a better therapy than currently approved Vertex's two drug combo Orkambi.  A once daily triple combo would be advantageous for CF patients that may take up to 20-40 pills per day for this disease. 

Interim Analysis of 2451 and 2222
According to Galapagos, an interim analysis will be conducted on the combo mid-year.  If the combo passes the safety test, then corrector #2 GLPG2737 will then be added to the mix, and the three drugs will be tested for CF patients with F508del around third quarter of 2017.  So, by the end of 2017, the first triple combination (one potentiator, and two correctors) will be tested.  However, if the current phase 1 clinical trial with 2451 and 2222, does not produce an acceptable drug/drug interaction safety profile in healthy participants, then the entire project would be delayed.   

CTP-656  in Phase 2
Concert Pharmaceuticals CTP-656 is currently in a phase 2 clinical trial as mono-therapy for CF patients harboring the G551D mutation.  The drug is dosed once daily, and has shown head to head comparison's with Kalydeco in several early clinical trials with PK advantage.  The drug could fit nicely into the mix for a combo also, with two correctors, dosed as one simplified daily pill for F508del CF patients. 

Bottom Line: 
We'll monitor progress of the Galapagos combo clinical trial (2451 + 2222), and CTP656's phase 2 clinical trial that is scheduled to complete by the end of 2017.  Thank you for reading. 

GLPG1837 for Cystic Fibrosis

Galapagos presented data at the 2016 NACFC conference in Orlando yesterday, with a focus on SAPHIRA (2) results with drug GLPG1837 for CF people with the S1251N mutation.

Galapagos Abstract 253
Phase 2 results from SAPHIRA (2) S1251N
The bottom line with this small clinical trial that included n=7 patients, was that the company monitored in line FEV1, but below expectations for sweat chloride (readings in naïve patients that have never received Kalydeco, did not show a reduction in sweat chloride when administered GLPG1837 for 7 days) both compared against what Kalydeco had previously achieved at two weeks, in clinical trials for similar CF patients.  Sweat chloride readings is a biomarker that the FDA will want to see in clinical trials, prior to any approval.
  
Phase 2 from SAPHIRA (1) for G551D 
The company will have top line results by the end of 2016.  The company mentioned that Kalydeco for similar patients in (G551D), the FEV1 was around 6% to 10% improvement at the two week timeframe.  So that may be seen as a close comparison for their top-line results.  Below is a new CF timeline schedule for the company.  

Timeline for Potentiators:
GLPG1837 Phase 2 SAPHIRA (1) G551D readout by end of 2016
GLPG2451 Phase 1 readout first half of 2017
GLPG3067 Phase 1 start in 2017  (NEW)

Timeline for Correctors:
GLPG2222 Phase 2 start Q4 2016
GLPG2737 Phase 1 start Q4 2016
GLPG2851 Phase 1 start 2017

Bottom Line:
GLPG1837 was the first potentiator to enter clinical trials as twice daily dosing for Cystic Fibrosis people.  The company should have a readout by the end of 2016 for n=27 phase 2 clinical trial SAPHIRA (1) participants of the G551D mutation.  This will be an important readout regarding the future of that drug.  Concert should be into a phase 2 clinical trial with drug CTP-656 for G551D participants in the next few months, with readout by the end of 2017.  Thank you for reading. 

Contact: 586-431-8000

GLPG2222 and GLPG2451 for Cystic Fibrosis

Galapagos updated their cystic fibrosis program.  The significant news today, was that the company was expected to test potentiator GLPG2451 with corrector GLPG2222, from a press release on June 15th.  Today, they have not made up their mind in full whether they are going to do a combination with 2451 and 2222, as potential for part of a triple combination.  GLPG2451 phase 1, will have a slight delay with results in early 2017, from expected end of 2016.   Thank you for reading.                                             

GLPG2222 and GLPG2451 for Cystic Fibrosis

In their most recent press release http://www.glpg.com/press-releases, dated June 15th, 2016, Galapagos (GLPG) reported the following. 
 
Galapagos reports that GLPG2222, the first early binding (C1) corrector, passed the safety hurdle in Phase 1 studies in healthy volunteers. GLPG2222 was tested in single ascending doses up to 800 mg, and in multiple ascending doses up to 600 mg qd for 14 days in a double-blind, randomized, placebo-controlled study. The candidate drug was shown to be well-tolerated and no emerging safety signals observed in the dose range studied. Absorption of GLPG2222 was rapid and favorable. Pharmacokinetics of GLPG2222 support once-daily dosing regimens to be explored in further development. Corrector GLPG2222 will be tested next with potentiator GLPG2451 in healthy volunteers. Corrector GLPG2222 is one of the potential modulator compounds for the triple combination therapy that Galapagos and AbbVie are developing, aiming to address 90% of all CF patients.

The corrector GLPG2222 is dosed once daily, and will now be tested with the potentiator GLPG2451 which is also a once daily dosing, in a phase 1 clinical trial for healthy volunteers, with readout by the end of 2016.  Thank you for reading. 

 

Galapagos Updates Cystic Fibrosis Program

Galapagos (GLPG) and AbbVie developed a partnership aimed at treating 90% of the Cystic Fibrosis population with a triple combination drug therapy.  The triple combo will involve a potentiator and two correctors for patients with the F508del mutation.  Under the agreement dated back to September of 2013, Galapagos leads discovery and development through phase 2, shares Phase 3 responsibility with AbbVie.  Below is a list of potential candidates that GLPG will be taking to the clinic for further exploration. 

Potentiators:
GLPG1837  Completed phase 1 multiple dosing trial, and heading into phase 2 for G551D and S1251N CF 2016.  
GLPG2451  Additional potentiator expected to move into a phase 1 clinical trial 2Q 2016.

Correctors:
GLPG2222  First generation corrector began dosing in healthy volunteers January.  Expects top line results in Q2 2016.  GLPG receives $10 million milestone from ABBV.
GLPG2851  Another first generation corrector, aiming to initiate phase 1, end of 2016.  
GLPG2665  Next-generation corrector, expected to enter phase 1, middle of 2016.  
GLPG2737  Next-generation corrector, expected to enter phase 1, Q4, 2016.  

Bottom Line:  It's good to see a company attempt to improve upon the currently approved combo Orkambi for Cystic Fibrosis people.  By the end of 2016, we should at least have some indication how corrector GLPG2222 and possibly GLPG2665 have done in phase 1 clinical trials.  Thank you for reading.