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Protalix Undervalued Due To Ghost Of Shire, Upside On Fabry Approval Significant

Christiana Friedman profile picture
Christiana Friedman


  • Protalix has a BLA already submitted with the FDA for the approval of PLX-102 for Fabry Disease.
  • Sanofi’s competitor, Fabrazyme, almost reached $1B in global revenue last year.
  • PLX-102 has significant advantages over Fabrazyme, including lack of immunogenicity and easier administration schedule.
  • The main risk is what happened to Shire in 2012 with a similar drug molecule for Fabry, which is why I believe the stock is trading very cheap here.
  • If Protalix can get past the ghost of Shire, now Takeda, and achieve FDA approval, the upside from here could be significant.

What would you value a developing biotech with BLA submission just filed with the FDA? In this case, a BLA filed for a drug with the potential to outcompete a Sanofi (SNY) near-blockbuster, and the company is flush with cash after closing a $44M private placement. Somewhere near all-time lows? That's where Protalix BioTherapeutics (NYSE:PLX) is, and to me, it looks unjustified, though understandable. If the FDA approves its BLA application for its Fabry disease drug, though, I believe the upside revaluation could be particularly significant.

Though there is one major hangup for the stock (I'll get into that in a minute), the lack of enthusiasm for a stock like Protalix in this particular scenario would make sense if the chances for approval were a long shot. It would also make sense if the chances for success in the market were slim, even if approval looked likely. If you look at the data and the partnerships involved, though, the drug in question, PLX-102, looks to have both a high probability of FDA approval and market success if approved.


Fabry disease is a genetic disorder affecting 1 in 40,000 people where they lack an enzyme that normally breaks down a fatty substance in the blood, preventing it from sticking to the arterial walls. People with this disease can’t break it down and it gets stuck, mimicking cardiovascular disease. Patients generally take enzyme replacement therapy once every two weeks, and the current market leader is Sanofi’s Fabrazyme. Fabrazyme is the most popular drug for Fabry disease, selling €410M and €813M worldwide (see page 64) last year, putting it just under blockbuster status.

The other option for patients is Galafold, which works differently. Developed by Amicus Therapeutics (FOLD), it is advantageous because it is an oral therapy. It works by binding to

This article was written by

Christiana Friedman profile picture
Being involved in the medical industry and patient care, I developed an interest in new therapies for diseases I come into contact with in my work. Fundraising for hospitals is part of my past, now semiretired from the medical field but staying in through retail investing.

Analyst’s Disclosure: I am/we are long PLX. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Comments (16)

kesegeo profile picture
Hello Christiana! The reason why Protalix undervalued made in the title of the article seems to be unconvincing, to say the least. Replagal was the first ERT for Fabry disease approved in 2001. It has been compared with placebo in two studies which measured the effects of Replagal on pain, its effect on the mass of the left ventricle (heart muscle), a measure of the amount of Gb3 in the heart cells involving a total of 40 male patients. A further study was carried out in 15 female patients. Fabrazyme was approved in 2 years through the FDA’s accelerated approval program which allows using surrogate or interim measures in a clinical trial. But this way requires confirmatory Ph4 trial which Fabrazyme failed to get through. So when Shire turned to the FDA for BLA, an additional study was required, given the extremely scarce data that allowed to get the right to sell Replagal in Europe. And Shire has withdrawn application not because it "wasn't worth it" (the US market is the biggest), but because there was no chance to pass additional study. Your phrase "Since PLX-102 and Replagal are based on the same molecule, it would stand to reason that PLX-102 could have similar problems getting approved" perplexed me. Please explain how the "same molecule" can slow down the annualized eGFR slope by 80% of the study participants from ‑5.90 mL / min / 1.73m2 / year while on agalsidase alfa to -1.19 mL / min / 1.73m2 / year on PRX -102 in all patients? PTX-102 in addition to those listed by you, has many other advantages compared to Repagal.


That is, comparing these two drugs is simply not serious.
OPRX-106 possible future treatment for Inflammatory bowel disease (IBD) not for "irritable bowel disease" (do you mean Irritable Bowel Syndrome ?)
NDHT profile picture
Very good points.
William Meyers profile picture
Very informative article. In addition to the Shire thesis, I think this company is simply not on many analysts' radar. Long.
What percentage of Fabry patients can get by with Galafold? Seems like the remainder is just a portion of a niche market, with other companies targeting this disease as well. All their other projects on hold, while they throw a Hail Mary to save the company. Is that an accurate characterization?
Tombelge profile picture
Galafold is only relevant to up to 30% of the total Fabry patient population because Galafold only works on Fabry patients with an amenable mutation.

Thus while PRX-102 would be directly relevant for the 70% of the total Fabry patients, it will also be relevant to those taking Galafold, but not necessarily seeing any benefits from it.

Thus realistically PRX-102 would be relevant to about 75-80% of the total Fabry patient population.
PLX_2_20 profile picture
In England, a higher portion of the Fabrys community has that amenable gene variant...like 42%. They say overall its like 32% have that amenable trait, but that doesn't include the reduction in those females who wish to have children and adolescents who aren't approved for that small molecule. So maybe 25% can take Galafold. Galafolds results are quite similar to Fabrazyme and Replagal, i.e., the eGFR slope is in the very high range and kidney dialysis/failure will be the eventual broken path taken. Moreover, vascular cell walls will continually slope downward on blood viscosity and cleaning. And, thats the true benefit and cost savings to humanity with patients infusing 102 over all other forms of treatment. Dialysis alone is started to get billed at 50k a pop and when 102 puts a stop/delays by 25 years.... it will truly be a blessing to patients, families, governments, insurance. Literally, Ive seen dozens of testimonies from families participating in the various PLX 102 trials and all are speaking of the wonders of 102!! World wins with 102 Infusions!
Excellent analysis as always.
There is of course the matter of future competition:
- Gene therapy products in phase 1/2 from Sangamo and Avrobio.
- Glucosylceramide synthase inhibitors: Venglustat (Sanofi, phase 2) and Lucerastat (Idorsia, phase 3).

Do you have any insight as to how they fare compared to PLX product?
William Meyers profile picture
Lucerastat: fabrydiseasenews.com/...
From the article, skipped from Phase 1 trial to Phase 3 trial, no Phase 2. But certainly a potential competitor.
Tombelge profile picture
Gene therapy products are still in earlier phases of development and even if all goes well with thier programs, these won't be available on the market for at least another 7-10 years. Not an issue for PLX at the moment. And gene therapy in Fabry has had very mixed results.
Tombelge profile picture
Regarding Lucerastat: Not really a competitor at all. I encourage you to look at my newly posted investorshub post. And regards Lucerastat specifically I provide the following extract from my mentioned post:


Phase III clinical trial endpoint is Pain which as described above is a subjective measure and not that great specifically regarding keeping patients alive.

Secondly the Phase III trial is investigating Lucerastat as a MONOtherapy vs placebo if you believe it. Which means that in the trial they are not even going to be giving ERT to the patients.

The prior Phase I which showed interesting results was at least in combination with ERT to provide some sort of support to the patients.

Thus the Phase III design is in a sense dooming the patients and their physicians to accepting providing no clinically beneficial product to the patients when there is some available and that the new monotherapy is not even being investigated to improve the basic important clinical outcomes of Fabry disease.

Not a good trial design.

Secondly, initially they planned to enroll 100 patients acorss 29 sites in 9 countries. We can see that hasn't worked well for them at all, as currently on the clinicaltrials website, they are now planning for 108 patients across 58 sites across 15 countries. But while 23 of the planned sites are still not yet recruiting.

Also Perhaps the increase of 8 is also due to drop-out of the initial patients?

This Phase III was started in May 2018.

With regards potential time-frame to completion let us remember that it took Protalix 3 years to recruit the 100 patients needed for the BALANCE and BRIDGE studies. And that was with good pre-clinical data on Heart, Kidney function and better than current ERT data from Phase I/II on eGFR slope data in humans.
BALANCE the largest of the PLX studies with 78 patients recruited from 51 sites across 21 countries.

So we can see that it's not going to be easy to get patients into this trial.

And we know this isn't working out for them as on that presentation that Dr Warnock made last December, he stated without mentioning the name that there was a study in Fabry looking to use Pain as its primary endpoint, but for which as per explained above they are having issues with enrollment, surprise surprise.

Thus given the May 2018 start, the minimum 3 years to recruit if all centres are online, but that presently half of them are not, would put the timing to enrollment at a logical 6 years, but then add the lower reason for patients and physicians to enter the trial would probably put enrollment at about 9 years, even as new sites come online?? Then the endpoint in pain is at 6 months, so we are looking at about 10 years to data from this study??

If PRX-102 is approved it will be even more difficult to find the patients physicians wanting to enter this monotherapy trial. Even if it does complete the data are largely meaningless without heart or kidney function assessment in addition to nothing to compare against."
PLX_2_20 profile picture
Nice article! A few possible corrections or insights. One, Fabrazyme and Galafold/migalastat, both, never achieved full FDA approval. Shire's ERT's Replagal alpha-gal closely/more so resembles the Fabrazyme/beta-gal ERT molecule (not the PLX's 102 plant derived [tobacco] enzyme that's pegulated). Replagal's clinical results did not meet endpoints (just like Fabrazyme) and was such a small trial (6 patients if my memory serves me) that it saw a few participants drop out, e.g., the FDA did not allow entry into the USA for redundancy and ineffectiveness.

Maybe, going back and mentioning the approval of Elelyso/Uplyso in the EU/FDA, the deal with PFE and Brazil for that ERT for Gaucher's, and their currently approved manufacturing and research facilities. Already having a approved ERT and a approved self manufacturing campus is a huge positive to the underlining stock valuations.

The true ghost that haunts PLX is.... who is it a threat too and who doesn't want to run P3 trials against PLX's 102 data. And, convertible notes!
NDHT profile picture
It looks like that they had $14 million cash as of March 31, with the addition of $44 million, they should have ~$50 million by the end of June. However, they do have debts ($52 million?) due withing one year. Not sure how they will address this problem, especially if something goes wrong.

Last thing we want to see is what happened to Synergy.
Tombelge profile picture
If the product is approved by the FDA in approx end 2020, then that will trigger a milestone payment, which is likely to be quite significant out of the 1 billion dollars Chiesi has earmarked in milestone payments to PLX on PRX-102. Thus that FDA approval milestone payment could be used to pay that off, + any other revenues that may begin as soon as the product is launched. Additionally it may very well be possible for PLX to negotiation the notes due to a later date, which may well be in the interests of three fold PLX, us shareholders and the noteholders who will convert at a higher price, if sales and all go well.
Jehrune profile picture
Thanks for the article. Together with significant management changes and some good decisions in general (recent partnership with Kirin shows the commercialization possibilities of ProCellEx), this is lining up to be a winner for the next year.
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