Genentech’s Not So Great UC Treatment Results

The latest round of the new trial results from Genentech’s UC treatment etrolizumab were disappointing, putting at risk a once promising treatment for this painful disease.

What is Ulcerative Colitis?

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that can cause intense pain and make it hard to digest food. It can affect people of any age but onset is often early in life.  Many patients begin to feel its effects between the ages of 15 and 30. It causes long-lasting inflammation and ulcers (sores) in the digestive tract, affecting the innermost lining of the large intestine (colon) and rectum.

As the disease progresses, symptoms usually develop and increase over time. Cases of advanced UC that occur suddenly are very rare. The effects of ulcerative colitis can be mild, causing bloating or intestinal discomfort.  They can also be quite debilitating and sometimes lead to life-threatening complications. While it has no known cure, proper UC treatment can greatly reduce symptoms and damage to the body caused by the disease. In some cases, treatments can completely stop symptoms and even cause long-term remission.

All inflammatory bowel diseases, of which ulcerative colitis and Crohn’s Disease are the most common, are serious. When any part of your digestive system is inflamed or damaged, it will lessen the quality of your life and can cause digestive issues. Long term damage can occur if aggressive UC treatment is not used. About 40% of patients have mild IBD, 35% moderate IBD, and 25% severe IBD. Many people don’t recognize IBD symptoms even though IBD is one of the most common disorders seen by physicians. There are not many effective treatments for those with the advanced form of the disease, which is why Genentech undertook development of its drug etrolizumab.

Causes and Risk Factors for Ulcerative Colitis

The causes of ulcerative colitis are well known. The disease occurs when your body’s immune system fails to recognize your digestive tract as part of your body. The immune system will normally attack invaders in your body, including viruses and bacteria. When someone has an IBD, the immune system attacks the good gut bacteria and the cells that line your colon because it thinks they are invaders trying to do you harm. The soldiers of your immune system are white blood cells and it is they that launch the attack.

Like many immune system diseases, the medical establishment is not sure why a perfectly functioning immune system becomes faulty and attacks what it is supposed to protect, but it might be in the genes because the disease tends to run in families and with certain groups. Risk factors that might indicate you have a higher likelihood of getting the disease include:

• Sex: Approximately 60% to 65% of individuals who report IBS are female.
• Ethnicity: The risk is highest in people of Ashkenazi Jewish descent.
• Age: It is most often diagnosed between the ages of 15 and 30 years old or older than 60.
• Personal History: Your risk could be up to 30% higher if you have a close relative with the condition.

It has been determined that neither food nor stress causes UC but they, along with Vitamin D deficiency, can trigger a flare-up.

Treatments for Ulcerative Colitis

Treatments for UC vary depending on the severity of the disease. If it is mild, treatments range from lifestyle changes including regular exercise, reduction of stress, and eating a healthier diet.

For mild to very severe cases medications and other treatments are available. Doctors may prescribe several treatments based on the symptoms the patient presents. Medications include:

• Antibiotics: For gut infections.
• Immunomodulators: These target your immune system to get it to stop attacking your gut.
• Biologics: Safer because they are made from proteins in living cells instead of chemicals.
• Loperamide. Diarrhea is a big problem and this drug can slow or stop diarrhea.
• Aminosalicylates: They are 5-aminosalicylic acid (5-ASA) and help fight inflammation and ease symptoms.
• Corticosteroids: Used in severe cases for short periods of time.

Although this current crop of treatments can often prove effective, too often patient symptoms are not alleviated and the disease can progress unchecked. Many companies have been working on advanced UC treatments; Genentech was taking a leading position with its drug etrolizumab.

Genentech’s UC Treatment Shows Poor Test Results

Genentech is one of the companies working on therapies to both prevent the disease from progressing and to ease the disease’s most painful and dangerous symptoms. Etrolizumab is Genentech’s first investigational dual anti-integrin studied in inflammatory bowel diseases (IBD). It is designed to target IBD on two fronts by selectively inhibiting α4β7 and αEβ7 to control both the trafficking of immune cells into the gut and their inflammatory effects on the gut lining. This type of drug is sorely needed as an alternative preventative and therapy.

The drug has shown strong promise in earlier trials for its use as a UC treatment and was part of the largest clinical trial program ever undertaken in inflammatory bowel diseases. However, the potential treatment showed poor results in its latest trial phase. These results are disappointing, to say the least, and point to the drug potentially not having the efficacy originally hoped.  Chief medical officer and head of Global Product Development for Genentech, Levi Garraway, said he was disappointed in the results from the study because people with ulcerative colitis need new treatment options. One bright spot is that there were no safety issues reported in the use of etrolizumab.

As the company analyzes the data, Genentech continues to be hopeful that etrolizumab will emerge as an investigational induction and maintenance treatment for those suffering from irritable bowel disease.

In the meantime, with millions of people suffering from this debilitating and advancing disease, the search for safe and more effective UC treatments continues.