Apitope moves Graves’ disease candidate toward Phase 2; a primer on autoimmune disease “for people in a hurry.”

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The News:

Apitope International NV has taken a step closer to developing the first new treatment option in decades for thyroid disorder Graves’ disease after posting positive results in a first-in-human trial of its ATX-GD-59 antibody.

The British-Belgian biotech said the Phase 1 trial shows signs of efficacy in the majority of patients with Graves, an autoimmune disease affecting up to 10 million people across the US and Europe that leads to an overgrowth of the thyroid gland.

Armed with the clinical data, Apitope said it intends to press on with a Phase 2 trial in the first quarter of 2019, giving it a second mid-stage clinical candidate in addition to multiple sclerosis therapy ATX-MS-1467, says FierceBiotech.

In Graves’ disease, the immune system mistakenly attacks the thyroid gland, causing it to become overactive and enlarged. Excess levels of thyroid hormones in turn can cause skin abnormalities, tremors, weight loss, osteoporosis and eye complications including blindness.

ATX-GD-59 is designed to reduce levels of thyroid hormones by targeting the underlying immunological basis of the disease and in the study was able to reduce levels of thyroid stimulating hormone receptor (TSHR) antibodies “with close correlations between percentage decreases in antibody and thyroid hormone levels in line with the mechanism of action.”

There are already drugs available such as methimazole and propylthiouracil that try to block the production of thyroid hormones, but these have a high failure rate, according to endocrinology professor Simon Pearce, MD, of Newcastle University in the UK, the lead investigator in Apitope’s trial.

Second-line treatment is limited to invasive surgery and radioiodine therapy to destroy the thyroid and means patients must take lifelong thyroid hormone replacement therapy, while in some cases surgery can result in scarring and vocal cord damage.

“ATX-GD-59 demonstrates the potential to address the high medical need for a new, safe and effective treatment for the neglected field of those suffering from Graves’ disease,” said professor Pearce.

Apitope’s decision to move ahead with the program comes against a backdrop of very little R&D effort in Graves’ disease and what seems to be some recent failures. GlaxoSmithKline spinout Thyritope Biosciences was launched in 2014 to work in this area, but now seems to be inactive. Novartis has also been developing CD40 antigen inhibitor CFZ533 in Phase 2 for the disease, but only lists organ transplantation as a target indication.

Last October, Apitope said it intended to raise new funds through an IPO on the Euronext exchange in order to provide funds for the development of its clinical pipeline, including the MS program and a third in uveitis–but hasn’t yet followed through on those plans.

Steve’s Take:

Given all the recent attention to the phenomenal breakthroughs in the immuno-oncology space, with checkpoint inhibitors like Merck’s Keytruda and CAR-T cell therapy like Novartis’s Kymriah, I thought it might be useful to focus briefly on autoimmune disease–a treatment field that doesn’t get nearly as much coverage.

With copious appropriation of some highly coherent elucidation from Healthline, here’s an ultrashort primer on auto-immunity to help shine a light on this often-misunderstood disease category.

So, what’s an autoimmune disease? It’s a condition in which your immune system mistakenly attacks your body.

The immune system normally guards against germs like bacteria and viruses. When it senses these foreign invaders, it sends out an army of soldier cells (also called killer T cells) to attack and destroy them. Normally, the immune system can tell the difference between foreign cells and your own cells.

In an autoimmune disease, the immune system mistakes part of your body–like your joints or skin–as foreign. It releases proteins called autoantibodies that attack healthy cells. Some autoimmune diseases target only one organ. Type 1 diabetes damages the pancreas. Other diseases, like lupus, affect the whole body.

Why does the immune system attack the body?

Doctors don’t know what causes the immune system to run amok. Yet some people are more likely to get an autoimmune disease than others. Women get autoimmune diseases at a rate of about 2 to 1 compared to men–6.4% of women vs. 2.7% of men. Often the disease starts during a woman’s childbearing years (ages 14 to 44).

Some autoimmune diseases are more common in certain ethnic groups. For example, lupus affects more African-American and Hispanic people than Caucasians. Certain autoimmune diseases, like multiple sclerosis and lupus, run in families. Not every family member will necessarily have the same disease, but they inherit a susceptibility to an autoimmune condition.

Because the incidence of autoimmune diseases is rising, researchers suspect environmental factors like infections and exposures to chemicals or solvents might also be involved. A “Western” diet is another suspected trigger. Eating high-fat, high-sugar, and highly processed foods is linked to inflammation, which might set off an immune response. However, this hasn’t been proven.

Another theory is called the hygiene hypothesis. Because of vaccines and antiseptics, children today aren’t exposed to as many germs as they were in the past. The lack of exposure could make their immune system overreact to harmless substances.

Bottom Line:

Researchers don’t know exactly what causes autoimmune diseases. Diet, infections, and exposure to chemicals all might be involved.

There are more than 80 different autoimmune diseases. But borrowing from astrophysicist Neil de Grasse Tyson, here are the most common ones for “people in a hurry.” (Graves and celiac have already been mentioned herein.)

  1. Type 1 diabetes

The pancreas produces the hormone insulin, which helps regulate blood sugar levels. In type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the pancreas.

High blood sugar can damage blood vessels, as well as organs like the heart, kidneys, eyes, and nerves.

  1. Rheumatoid arthritis

In rheumatoid arthritis (RA), the immune system attacks the joints. This attack causes redness, warmth, soreness, and stiffness in the joints. Unlike osteoarthritis, which affects people as they get older, RA can start as early as your 30s.

  1. Psoriasis/psoriatic arthritis

Skin cells normally grow and then shed when they’re no longer needed. Psoriasis causes skin cells to multiply too quickly. The extra cells build up and form red, scaly patches called scales or plaques on the skin. About 30% of people with psoriasis also develop swelling, stiffness, and pain in their joints. This form of the disease is called psoriatic arthritis.

  1. Multiple sclerosis

Multiple sclerosis (MS) damages the myelin sheath–the protective coating that surrounds nerve cells. Damage to the myelin sheath affects the transmission of messages between your brain and body. This damage can lead to symptoms like numbness, weakness, balance issues, and trouble walking. The disease comes in several forms, which progress at different rates. About 50% of people with MS need help walking within 15 years after getting the disease.

  1. Systemic lupus erythematosus (lupus)

Although doctors in the 1800s first described lupus as a skin disease because of the rash it produces, it actually affects many organs, including the joints, kidneys, brain and heart. Joint pain, fatigue, and rashes are among the most common symptoms.

  1. Celiac disease

People with celiac disease can’t eat foods containing gluten — a protein found in wheat, rye, and other grain products. When gluten is in the intestine, the immune system attacks it and causes inflammation. Celiac disease affects about 1 percent of people in the United States. A larger number of people have gluten sensitivity, which isn’t an autoimmune disease, but can have similar symptoms like diarrhea and abdominal pain.

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