GLPG1837 for Cystic Fibrosis

Galapagos released phase 2, SAPHIRA(1) results this week with drug GLPG1837, for Cystic Fibrosis patients with the G551D mutation.  The link to the conference call is here http://edge.media-server.com/m/p/aen3zb2d.

Some details from the conference call:

• The company reported similar ppFEV1, in comparison to FDA approved Kalydeco
• Kalydeco patients at baseline had a sweat chloride reading of around 45 mmol/L
• After the seven day washout period, the sweat chloride level increased to a mean value of 98 mmol/L*
• After 28 days, and dosing up to 500 mg GLPG1837 twice daily, sweat chloride fell to 66 mmol/L
• For patients who exceeded the predicted target concentration, sweat chloride changed from a mean 94 mmol/L to 52 mmol/L
• Sweat chloride did not fall to the original baseline Kalydeco level, of around 45 mmol/L
• GLPG1837 was mentioned as being dose limited up to 600 mg twice daily

* The concentration of chloride in sweat is elevated in individuals with CF.

Thank you for reading.               

CTP-656 Clinical Trial Initiated

CTP-656 for cystic fibrosis patients with CFTR gating mutations is now loaded in the clinicaltrials.gov website here NCT02971839.  The phase 2 trial is expected to start enrollment in January of 2017 to avoid the busy holiday season approaching.  The readout completion date is by the end of 2017.  Sweat chloride will be the primary endpoint of the study with FEV1 secondary.  With only 6-8 patients in each arm, the trial is not specifically powered for efficacy, but more likely to compare the three different dosages, and decide which one will be taken further into a phase 3 clinical trial, where FEV1 will be the primary endpoint.

Estimated Enrollment:	40
Study Start Date:	January 2017
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CTP-656, Dose 1, QD Oral tablet dosed once-daily for 28 days	Drug: CTP-656, Dose 1 (QD)
Experimental: CTP-656, Dose 2, QD Oral tablet dosed once-daily for 28 days	Drug: CTP-656, Dose 2 (QD)
Experimental: CTP-656, Dose 3, QD Oral tablet dosed once-daily for 28 days	Drug: CTP-656, Dose 3 (QD)
Active Comparator: Kalydeco, 150 mg Tablet (open label) 150 mg, oral tablet dosed twice-daily for 28 days	Drug: Kalydeco, 150 mg Tablet (BID; open-label)
Placebo Comparator: Placebo, Oral Tablet, QD Oral tablet dosed once-daily for 28 days	Drug: Placebo (QD)

Detailed Description:

This is a randomized, parallel-group, double-blind, placebo controlled multicenter study to evaluate the safety and efficacy of CTP-656 in CF patients with CFTR gating mutations, compared to Kalydeco, for a total of 28 days. Subjects will be randomized to receive either double-blind CTP-656 or placebo, or open-label Kalydeco.

 

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

Kalydeco for G551D

Vertex Pharmaceutical's Cystic Fibrosis drug Kalydeco has been FDA approved for people with the G551D mutation since 2012.  Kalydeco has been proven very effective for these patients, as the results from clinical trials reveal.  Below (Vertex 2012 presentation) is sweat chloride, and FEV1 results from the phase 3 G551D clinical trial that led to FDA approval.

 

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The results above at 24 and 48 weeks show extremely sustainable efficacy, versus placebo. Other improvement considerations, would be the dosing of once daily to improve adherence, and bio-availability for oral consumption, with  low or moderate fat containing food.  Kalydeco is currently dosed 150 mg every 12 hours, and prescribed to be taken with fat-containing food. Thank you for reading. 

 

Contact: 586-431-8000                            

Is Adherence to Ivacaftor Suboptimal

From a recent issue of the Journal of Cystic Fibrosis, the authors make a strong case that twice daily Ivacaftor adherence is suboptimal.  Although used interchangeably, let's attempt to differentiate between compliance and adherence. If a doctor prescribes Ivacaftor 150 mg twice daily, and you accept and fill the prescription, you are in compliance with your doctor. Taking Ivacaftor twice daily is adherence to the prescription requirements.  The link to the article is below.  
Adherence_to_Ivacaftor_is_suboptimal
In the small sample study, the authors found that adherence was 61% among patients prescribed Ivacaftor.  Keep in mind they studied patients taking Ivacftor for the G551D mutation, which showed an improvement of over 10% percentage points in clinical trials, in the percent predicted FEV1.  The latest  FDA approved combo Orkambi (Ivacaftor and Lumacaftor) scored much lower on FEV1 for patients with F508del, than what Ivacaftor alone did for G551D patients. There are a few companies currently working on a once daily for CF patients, which could increase adherence rates to a higher level. Thank you for reading.