A great Biotech investment opportunity: Amicus Theraputics (NASDAQ: FOLD) - Migalastat HCl for Fabry Disease

Amicus Therapeutics (NASDAQ: FOLD) is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule, orally administered drugs known as pharmacological chaperones, for the treatment of a range of human genetic diseases.

Amicus (NASDAQ: FOLD) is focused on three key strategic priorities:

• The Phase 3 development of its lead program, AT1001 (migalastat HCl) for the treatment of Fabry disease;

A Quick overview of Fabry Disease

• Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called α-galactosidase A (α-GAL). 

Nature.com

• The role of α-GAL within the body is to break down a complex lipid called globotriaosylceramide (GL-3).  Reduced or absent levels of α-GAL activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. 

• This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including

• Pain
• Kidney failure
• Increased risk of heart attack and stroke.

• Most individuals with Fabry disease have missense mutations in the GLA gene. Missense mutations can alter the structure of α-GAL, which results in the accumulation of the enzyme in endoplasmic reticulum (ER).

• As a result of the accumulation of α-GAL in the ER, the enzyme is unable to reach the lysosome, the part of the cell where α-GAL does its work of breaking down substrate.

Market opportunity 

• It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. The market opportunity is endless with number of Fabry patients on treatment projected to grow by 12%.

• Fabry disease is an X-linked recessive genetic disorder that affects both men and women. 

Amigal (migalastat HCl)

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=47206758

Migalastat HCl bind to destabilized α-galactosidase A enzyme (α-GAL) and thereby restore its intended biological function of degrading globotriaosylceramide (GL-3) substrate in lysosomes. 

Amicus completed multiple Phase 2 studies of AT1001 for the treatment of Fabry disease. 
In total, 26 male and female subjects were treated for either 12 or 24 weeks. 
Twenty-three of the 26 subjects continued to receive treatment in an ongoing Phase 2 Extension Study designed to evaluate the long-term safety and efficacy of AT1001.
Results from the Phase 2 studies of Amigal indicated that there were no drug-related serious adverse events. The most common adverse events were headache, arthralgia and diarrhea.  
In subjects identified as responders to AT1001, treatment resulted in increased levels of the target enzyme (α-Gal A), as measured in white blood cells and in the kidney, and reduced levels of the target substrate (GL-3), as measured in renal interstitial capillary cells from kidney biopsies and in urine.
Additional preliminary results from Phase 2 extension study showed that eGFR has remained stable out to 2-3 years for all subjects continuing in the extension study and the average annual rate of change in eGFR in subjects identified as responders to migalastat HCl, excluding hyperfiltrators, was +2.0 mL/min/1.73m2.  Additionally, trends of reduced proteinuria continued to be observed in subjects identified as responders to AT1001

Phase 3 design:

• Purpose: compare the effect of AT1001 (migalastat hydrochloride) versus placebo on kidney globotriaosylceramide (GL-3).
• Study design: double-blind, randomized, placebo-controlled study will be conducted in 60 patients at approximately 40 sites worldwide. The study will consist of two stages and an open-label treatment extension phase
• Primary outcome: kidney GL-3 (assessed histologically in kidney biopsy samples)
• Secondary outcome:  urine GL-3 levels, renal function (assessed by iohexol GFR, eGFR, and 24-hour urine protein) , and safety and tolerability
• Estimated Primary completion date: July 2012
• For more info: http://clinicaltrial.gov/ct2/show/NCT00925301?term=NCT00925301&rank=1
• Results expected in 3Q of 2012. It is also being evaluated in different indication in Study 013 with results expected in 3Q-4Q of 2012.

In terms of fundamentals of this company, they have $108.2M in cash as of March 31, 2012. The company is planning on spending around $37-43M in R&D.  I do not believe the company will need additional capital through its Phase 3 data release and/or NDA submission. 

From the Phase 2 results, and the design of Phase 3 trial, I believe the data should be positive. Since 65% of the patients from phase 2 remained on the migalastat HCl monotherapy shows a strong efficacy and safety in this patient population. So far from the observation, there is low dropout rate which significantly strengthens the potential for positive data of phase 3 trial. In addition, GlaxoSmithKline invested additional $18.6million equity investment in this company which now brings their ownership to 19.9%. With positive phase 3 result, they may buyout this company due to its smaller size. 

In my opinion, this company should do well in near term as it approaches its phase 3 data release. I strongly believe that the share prices should reach $7-9 with positive result but once again we should see more momentum in share price as the company updates on specific date of data release.  Once again, this company can possibly be bought out by GlaxoSmithKline on a positive result and its deep pipeline with various candidates.

Price target: $8 

Disclosure: Long 

Resources: Amicus Theraputics Website, Reuters, Stockcharts, Clinicaltrial.gov, Pubmed Chemical, and nature.com