Evaluation of tafamidis as first-line therapeutic agent for transthyretin familial amyloidotic polyneuropathy

Figures & data

Figure 1 (A) Line drawing of tafamidis. (B) Structural model of how tafamidis is envisioned to bind to TTR.

Note: While two binding sites are shown binding in the first site makes the second site allosterically unavailable. Reprinted from Johnson SM, Connelly S, Fearns C, Powers ET, Kelly JW. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug. J Mol Biol. Copyright © 2012,with permission from Elsevier.⁴⁶
Abbreviation: TTR, transthyretin.

Table 1 Comparison of clinical changes over 18 months in FAP patients receiving tafamidis or placebo

	Intention-to-treat
	#	# completing	NIS-LL*	NIS-LL % responders**	TQOL‡	Σ3 NTSF‡‡	Σ7 NTs†	mBMI††
Tafamidis	65	48	+2.8	45	+2.5	+0.3	+1.5	+39
Placebo	63	47	+5.8	29	+8	+1.6	+3.1	−33
P-value			0.027	0.068	0.21	0.005	0.066	0.0001

Notes:

* NIS-LL Neuropathy Impairment Score-Lower Limbs: motor, sensory, reflex; the greater the score the greater the impairment;

** NIS-LL responder: increase < 2 points in course of study; a primary endpoint in the study;

‡ TQOL Norfolk quality of life diabetic neuropathy questionnaire: higher the score the worse the quality of life; a primary endpoint in the study;

‡‡ Σ3 NTSF Summated values of three small fiber functions: the higher the number the worse the function; secondary endpoint;

† Σ7 NTs: summated values of seven tests of large fiber function: lower is better than higher; secondary endpoint;

†† mBMI, modified Body Mass Index is calculated by multiplying MBI by serum albumin in g/L developed for the evaluation of FAP patients as candidates for liver transplantation. It is a measure of wasting and malnutrition that appears to be based on gastrointestinal autonomic dysfunction. Higher scores are associated with better metabolic status and predict better outcomes after liver transplantation for FAP. Secondary endpoint.

Abbreviation: #, number of subjects.

JohnsonSMConnellySFearnsCPowersETKellyJWThe transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drugJ Mol Biol201218520322244854

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