Alopecia Areata Clinical Trial Comparison

Concert Pharmaceuticals, just released CTP-543 Phase 2 Results for patients with moderate to severe Alopecia Areata. The phase 2 results included the 12 mg cohort of the clinical trial, in addition to the already completed 8 mg results. Below are comparison's made with Pfizer's drug PFE-06651600 Phase 2 Alopecia Areata. As seen by the data below, Concert's CTP-543's 12 mg results are shown to be the most efficacious versus their own 8 mg arm, and against Pfizer's PFE-06651600 at 24 weeks. The SALT % Increase (mean) drop from baseline (CTP-543 SALT dropped- 50%), is on a percentage basis the largest SALT improvement of the three results below. Results below are relative improvement from baseline, not placebo adjusted.

• SALT Score of 100 = zero hair growth
• SALT Score of 0 = full hair growth 

The percentage drop of SALT score (hair growth improvement) is one of the tools used to evaluate the efficacy of different Alopecia clinical trial drugs. Next CTP-543 will be tested in two large phase 3 clinical trials, but that won't occur until around mid 2020. 
                                                                  

PFE-06651600
	Total (n=45) at 24 weeks
		Baseline	End of Treatment
SALT (mean)		88.1	54.5
SALT Increase (mean)		-33.6
SALT % Increase (mean)		0	38.1%
% SALT Reduction		% of 45 Patients Achieving Better SALT Scores
30%			47.9%
50%			37.5%
75%			27.0%
90%			25.0%
100%			12.5%
CTP-543 8mg
	Total (n=38) 24 weeks
		Baseline	End of Treatment
SALT (mean)		89.1	51.7
SALT Increase (mean)		-37.4
SALT % Increase (mean)		0	42.0%
% SALT Reduction		% of 38 Patients Achieving Better SALT Scores
30%			not measured
50%			47.0%
75%			29.0%
90%			16.0%
CTP-543 12mg
	Total (n=36) 24 weeks
		Baseline	End of Treatment
SALT (mean)		87.3	43.6
SALT Increase (mean)		-43.6
SALT % Increase (mean)		0	50.0%
% SALT Reduction		% of 36 Patients Achieving Better SALT Scores
30%			not measured
50%			58.0%
75%			42.0%
90%			36.0%

Smoking Cessation and AXS-05

A phase 2 Smoking Cessation trial with AXS-05 was completed in April of 2019 by Axsome Therapeutics and sponsor Duke University here Phase 2 Smoking Cessation. From the Axsome press release following results, a quote by James Davis of Duke University and principal investigator of the phase 2 clinical trial had the following to say.
"The findings in this trial are notable because AXS-05 was compared to bupropion, an approved treatment for smoking cessation," said James Davis, MD, Medical Director of the Duke Center for Smoking Cessation, and principal investigator of the trial. "The improvement of AXS-05 over bupropion observed in this trial is similar in magnitude to the improvement over placebo reported for the approved smoking cessation treatment varenicline in studies with a similar design. Reduction in ad-lib smoking was selected as the primary endpoint in this trial, because it has been shown to correlate with smoking abstinence. I look forward to the continued evaluation of AXS-05 as a smoking cessation treatment."
Varenicline is also known under commercialization as Chantix. The drug was developed by Pfizer, and FDA approved in 2006, with patent extending to 2020. After 2020 generic companies can replicate the drug and sell it at much lower prices. The drug has produced annual revenues of around $1 billion for Pfizer, even though the safety profile has come under scrutiny from the FDA. The side effect profile for Chantix is below. 
The most common side effects of CHANTIX include nausea (30%), sleep problems (trouble sleeping, vivid unusual strange dreams) constipation, gas, and/or vomiting.
The potential opportunity for Axsome Therapeutics with AXS-05, would be exhibiting similar efficacy as Chantix has in clinical trials, but with fewer side effects associated with treatment. Current chart below.

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CTP-543 and PFE-06651600

Now that Concert Pharmaceuticals has press released their top line results for CTP-543 8mg twice daily, CTP-543 Results from Interim Analysis of Phase 2a Trial in Patients with Alopecia Areata, a comparison can be made with Pfizer's  phase 2 results for drug PFE-06651600 for moderate to severe Alopecia Areata. In the comparison below, I am focusing on SALT % Increase (mean) End of Treatment. In this category CTP-543 had a 42.00% mean increase of SALT score after 24 weeks, versus a 38.13% increase for Pfizer's drug PFE-06651600. Concerts phase 2 study testing up to 8mg, may not be the highest dose available, as the company is currently testing a 12mg arm in the same phase 2 study.

PFE-06651600
	Total (n=45)	24 weeks
	Baseline	End of Treatment
SALT (mean)	88.1	54.5
SALT Increase (mean)	-33.6
SALT % Increase (mean)	0	38.13%
% SALT Reduction		% of 45 Patients Achieving Better SALT Scores
30%		47.9%
50%		37.5%
75%		27.0%
90%		25.0%
100%		12.5%
CTP-543 8mg
	Total (n=38)	24 weeks
	Baseline	End of Treatment
SALT (mean)	89.1	51.7
SALT Increase (mean)	-37.4
SALT % Increase (mean)	0	42.00%
% SALT Reduction		% of 38 Patients Achieving Better SALT Scores
30%		not measured
50%		47.0%
75%		29.0%
90%		16.0%
100%		0.0%

Janus Kinase Inhibitors for AA

The race is on for an effective and safe drug to treat Alopecia Areata. The two companies at the foremost of drug discovery are Pfizer with drug PF-06651600 and Concert Pharmaceuticals with CTP-543.  So how do the two JAK Inhibitor drugs stack up in limited clinical trials to date.
Columbia University 20 mg bid Ruxolitinib
n=12
% SALT Score Improvement (mean)
66.9%

Liu, King Study 10 mg bid Ruxolitinib
n=8
% SALT Score Improvement (mean)
61.2%

Pfizer PF-06651600
n=45
% SALT Score Improvement (mean)
38.1%                                                               
Next we will add the results of Concert's phase 2 clinical trial of CTP-543 with the 4mg and 8mg doses once press released expected fourth quarter. Thank you for reading.

Pfizer's PF-06651600

Pfizer and Concert Pharmaceuticals are the two companies with the most advanced drugs for the indication of Alopecia Areata. Pfizer has press released results for their lead candidate PF-06651600 here Phase 2 Data in Alopecia Areata. The drug achieved a -33.6 reduction in SALT score at 24 weeks from a baseline of 88.1. Below are the percentages of reduction of SALT score points for both Pfizer drugs. PF-06651600 is the drug that the company will be taking forward into phase 3 clinical trials.
  
Table. Percentage of Patients with Better SALT Scores at Week 24 Weeks
Improvement in SALT ScorePF-06651600 Group %, PF-06700841 Group, %

30%                                                 47.9                                  59.6   

50%                                                 37.5                                  48.9

75%                                                 27.0                                  38.3

90%                                                 25.0                                  31.9

100%                                               12.5                                   12.0

In the Columbia University phase 2 clinical trial Ruxolitinib for Alopecia Areata, 20mg bid dosing achieved good results based on the percentage of SALT improvement from baseline. At this time we do not know what the maximum dose that the FDA will allow Concert to run in clinical trials, as it is currently testing 8mg. CTP-543 is the deuterated version of Ruxolitinib currently in phase 2 clinical trials for Alopecia Areata. Thank you for reading.