Friday, October 9, 2015

CTP-656 & GLPG1837 Drug Comparison

The North American Cystic Fibrosis Conference began yesterday.  Concert presented some new data for CTP-656, and Galapagos released phase 1 data for drug GLPG1837 today. Below is new data for drug GLPG1837, and an early comparison of CTP-656 and GLPG1837.

GLPG 1837
The half life (t 1/2) of 1837 runs between 6 and 15 hours depending on the dosage.  I selected a middle of the range dosage of 500 mg used in the phase 1, for comparison to CTP-656, regarding plasma concentration, and their distinct profiles.  

Plasma concentration 500 mg 12 hours fed around 200 (ng/mL) 
http://www.glpg.com/rd-cystic-fibrosis
 
CTP-656
The half life of CTP-656 is 15 hours with a 150 mg dose.  
plasma concentration 150 mg 12 hours fed 1306 (ng/mL)

Kalydeco
The half life (t 1/2) of Kalydeco is around 11 hours for a 150 mg dose.
plasma concentration 150 mg 12 hours fed 412 (ng/mL)

SAFETY PROFILE
-Concert said CTP-656 was similar to Kalydeco at all dose levels, and well tolerated up to 300 mg.
-Galapagos 500 mg dosed twice daily with six participants, all experienced tiredness, and five experienced headache, in healthy subjects.  Galapagos says final safety data is pending.

Bottom Line:
From the data above, it looks like GLPG1837 will have to be dosed twice daily judging by the half life range of 6-15 hours, and Galapagos did not breakout each individual dose with half life. Two distinct drugs, as plasma levels with CTP-656 150 mg at 12 hours is substantially higher than GLPG1837 500 mg.  Concert believes that QD dosage (once daily) is possible with CTP-656.  The company still has to run a multiple ascending dose phase 1 trial, evaluating CTP-656 against Kalydeco.  Galapagos plans to initiate a phase 2 clinical trial for CF patients by the end of 2015. Thank you for reading.  No positions in Galapagos.  
 

Monday, October 5, 2015

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.