When diseases aren’t caused by chemicals, external allergens or other living organisms like viruses or bacteria, surely the symptoms are limited? Wrong. Painful and dangerous, inflammation can arise out of the blue – and treatment of such diseases is difficult.
The body’s immune system can be equally as toxic to foreign organisms as it can to its own tissues. A hyperactive immune system, or having certain over-sensitive types of antibodies, can wreak havoc on the body.
We discuss many well-known Autoimmune disease on a regular basis, such as Multiple Sclerosis (attack of the myelin sheath of nerve cells), Diabetes mellitus type 1 (attack of the pancreatic cells which secrete insulin) and Rheumatoid arthritis. Last week was World Lupus Day, and Lupus erythmatosus is another such example of the body’s fight against itself (read more here).
And I’ve also looked into a couple of examples for Rare Disease Day. But there are still many we do not hear about often enough.
So here I’ve tried to outline 7 other Autoimmune diseases that are less well known in Biotech….
P.S. It is often the case that these diseases occur together, as different symptoms arise in different organs which are afflicted by the same set of antibodies.
Various types of autoimmune antibodies can cause inflammation of the thyroid gland, which in response causes deregulation (such as under or oversecretion) of the hormone thyroxine.
Grave’s Disease is when antibodies behave like the stimulatory pituitary hormone (TSH), which causes the thyroid to secrete too much – and this can be incredibly serious. Typically this condition requires ablation of the gland (or resection) and then life-long hormone replacement therapy…going from excess (hyperthyroidism – and in extreme cases, a Thyroid Storm) to too little (hypothyroidism).
Generally you don’t hear about thyroid disorders in biotech unless it’s in relation thyroid cancer…and from my understanding the cheap and easy production of synthetic thyroxine (e.g. Levothyroxine) means finding a cellular therapy for the auto-antibodies is less of a priority.
This is understandable to an extent, as once patients with Grave’s have had the thyroid gland removed, treatment of hypothyroidism is considerably easier than treating certain cancers (for example). Still, Endocrinology is an incredibly complex and nuanced field, and there is an increasing number of patients for which ‘synthroid‘ treatment does not work.
This has therefore led to the search for other sources of hormone extract which works better (such as the traditional Pig extract which contains both types of thyroxine hormone – dubbed ‘Armour’ by Forest Pharmaceuticals). Anyway…it’s a pretty sensitive topic (no pun intended) which I will try and explore better in another article.
One mis-conception of dermatological conditions like Psoriasis is that is mostly just cosmetic damage and discomfort the skin plaques cause, but this is not true. Like with burn victims, during flare-ups the percentage coverage of skin which is affected can also be very serious, leaving patients unable to regulate their body temperature normally and vulnerable to life-threatening infections.
Today better palliative care is available, along with better ‘controls’ of the flare-ups (mostly pharmaceutical – but also via UV light therapies). Regarding therapeutics, there are also several biotechs with ongoing trials in the EU.
Here’s a quick animation of some of the symptoms in Psoriasis (and Psoriatic arthritis)…
These include trial therapy and research from dermatology specialist Leo Pharma in Denmark, the Zurich-based Delenex Therapeutics (which has a Phase Ib/IIa intradermal candidate) and Sweden based Affibody (our last Biotech of the Week). Switch Biotech in Germany also has a Phase I and pre-clinical programme for psoriasis.
Big Pharma players include Samsung Bioepis which has just gotten EMA approval for a biosimilar of Janssen’s Remicade, and AbbVie’s blockbuster Humira, which has a rival biosimilar in Phase III from Merck. Novartis already has FDA approval of their secukinumab for moderate to severe cases.
Although this is just mentioning a couple of examples. You can read more on the National Psoriasis Foundation.
As a general term for the inflammation of the uvea, optic nerve and vitreous of the eye, the general treatment of Uveitis is corticosteroid (anti-inflammatory) eye drops. It can be caused by a variety of other autoimmune diseases including Crohn’s (which we discuss a lot in Biotech) and sarcoidosis, yet is the eye inflammatory disease responsible of 10-15% legal blindness in developed countries.
Novartis’ secukinumab is also being investigated for uveitis (as well as Psoriasis), and is an antibody which binds to interleukin (IL)-17A.
AbbVie on the other hand has a Phase III adalimumab trial ongoing. And TxCell, from Nice (France), has been granted EU and US Orphan Drug Designation for its T-cell based therapy for autoimmune uveitis. Then there is Apitope in the UK, which has a T-cell platform immunotherapy which is also being investigated for Psoriasis and Grave’s disease.
Sarcoidosis is one example of a less-well understood inflammatory condition, whereby inflammatory cells build up in certain tissues (particularly the lungs) to form granulomas. These most commonly cause respiratory problems and chest pain, although they can also occur in any other tissues, including the brain (which can obviously be very serious…).
Janssen has investigated Remicade (infliximab) for pulmonary sarcoidosis, and acquired Centocor Inc. (which in 2014 also trialled the antibodies ustekinumab and golimumab in a Phase II).
Celgene (US) has also had a rich history with investigating therapeutics for sarcoidosis, although most trials were withdrawn (for various reasons). This included an effective Phase III small-molecule inhibitor (CC-100004), which although worked to reduce inflammation in sarcoidosis, unfortunately also had various adverse effects limiting its use.
AbbVie’s Humira (adalimumab) was also proposed for a trial in sarcoidosis by the University of Chicago, but terminated due to the failure to recruit enough patients in 2011.
This can cause a range of symptoms including weakness (due to a lack of adrenaline and cortisol), pain, low blood pressure (due to salt loss) and hyperpigmentation of areas of the skin. Crises can also occur when the hormone levels drop too low.
Although treatable with regular hormone replacement therapy (i.e. to replace coritsol), life-long treatment can be cumbersome and similar to diabetics, patients sometimes have to carry around syringes of cortisol for emergency use.
As far as I can tell, use of biologicals to treat Addison’s faces the same situation as for Thyroiditis and Grave’s disease: although hormone replacement therapy is life-long, finding an antibody therapy to help manage Addison’s is less of a priority compared to other Autoimmune indications. Nonetheless, I would be interested to hear of any such trials run by biotechs on this indication.
Vitiligo is often mistaken for hyperpigmentation of the skin, but is in fact the opposite – the loss of skin pigment. Phototherapy and topical agents such as corticosteroids are normally prescribed, but there is still no effective and safe treatment for this disease.
Leaving aside short term side effects (such as sunrush/erythema and sunburn) which are reversible and infrequent, the main problem with phototherapy is represented by the cumulative long term effects of UV therapy. This can cause premature ageing of the skin and an risk of skin cancer. Therefore, the aim is to get the best results from phototherapy whilst limiting its length.
The University of Navarra is one example of an institution looking at grafting of autologous (patient derived) melanocytes into afflicted areas of skin in a Phase I/Phase II. Otherwise, an Australian biopharma Clinuvel Pharmaceuticals has a candidate called SCENESSE – a chemical analogue of α-MSH which was recently granted EMA authorisation.
Granulomatosis is a type of vasculitis which encompasses many syndromes and diseases, some of which are poorly understood and have no clinical trials in place (e.g. Cogen’s Syndrome). Caused by the inflammation of blood vessels, the symptoms can arise in multiple tissues and cause many knock-on pathologies.
To find out about some of these diseases, you can read more on Vasculitis UK.
The biotech Kineta (in the US) and the University of Groningen (Netherlands) were researching a drug derived from Sea Anenomes (Dalazatide). It was found to have positive effect on a complication derived from Granulomatosis with Polyangiitis diseases.
The NIAD has also run multiple trials for the disease: Phase I trial for rituximab in patients with relapsed cases, as well as a trials of daclizumab for Wegener’s Granulomatosis. It seems as there is a strong case for biologicals in the treatment of this spectrum of diseases.
But instead, what I found when writing this short review, was that it surprising how large a gap in the Biotech field there was for Endocrine disorders (like Addison’s and Grave’s). It would be interesting to hear some of your thoughts on this!