Interleukin receptor mutation found

A variety of media outlets have covered the new research that has found a gene mutation relating to the inflammation protein interleukin-23. (The roles of the different interleukins are summarised in the Wikipedia.) In this study, the DNA of people with Crohn's was compared with that of people without Crohn's. A mutation in the interleukin-23 receptor was one of their findings.

The BBC notes:

The fault is in a gene receptor present in healthy people without inflammatory bowel disease but rare in those with the condition.

Further background is provided by the Baltimore Sun:

In 2001, scientists identified the first major gene underlying Crohn's disease. Called Nod2, the gene regulates the immune system's response to bacteria in the gut. People with one flawed copy have twice the normal risk of developing the disease, researchers found. Two flawed copies and the risk jumps 20- to 40-fold.

Researchers have since uncovered a handful of other suspicious gene mutations thought to play a role in inflammatory bowel disease. But the new finding marks the first time researchers have identified a mutation that may actually help protect against Crohn's.

The potential result of this finding is better drug therapies, eventually.

Natalizumab long-term remission results

Elan and Biogen Idec announced that a trial has found that natalizumab (sold as TYSABRI) maintained remission in Crohn's disease patients treated for longer than 2 years.

93% of TYSABRI patients who were in remission at month 12 of ENACT-2, were still in remission following 6 additional TYSABRI infusions in the open-label extension study and 86% were still in remission after 12 additional infusions.

These results were based on approximately 90 patients who were in remission after 15 months of continuous TYSABRI therapy in the ENACT-1 and ENACT-2 trials and elected to enroll in an open-label extension trial. A subpopulation of 22 patients was previously exposed to infliximab therapy. In this subpopulation, 91% were in remission after additional 6 and 12 infusions of TYSABRI, and 82% who had previously failed therapy with infliximab were in remission at the same time points.

"What is truly exciting is that patients who enter remission on TYSABRI may remain in remission in the long-term without loss of efficacy over time. These data are a significant advance for the field and suggest that TYSABRI may be an alternative biologic outside the anti-TNF class for patients suffering from Crohn's disease," said Remo Panaccione MD, Director, Inflammatory Bowel Disease Clinic, University of Calgary, Calgary, Canada, who presented the data at UEGW.

Natalizumab, like infliximab, is a monoclonal antibody (all generic medicine names ending in -mab are monoclonal antibodies). It is also used to treat multiple sclerosis, but was withdrawn from market in 2005 due to safety concerns. In mid 2006 it was reapproved for use in the US and Europe. More details are in the Wikipedia.

Prochymal phase II trial results

Osiris Therapeutics have announced encouraging results from their small trial of Prochymal in patients who had failed to respond to standard treatments.

Prochymal is a preparation of mesenchymal stem cells specially formulated for intravenous infusion. The stem cells are obtained from the bone marrow of healthy adult donors.

Comments were made by the lead investigator, Dr. Jane Onken:

“To understand the significance of this trial, it is important to appreciate just how sick these patients were,” said Dr. Onken. “On average, they had suffered with Crohn’s disease for 14 years and were unable to find relief with currently available therapy. It was in this difficult-to-treat population that we observed clinical improvement upon administration of the stem cell therapy.”

The Baltimore Sun had a talk with one of the participants of the trial:

The change, he said, began sometime in May, about eight weeks after he'd received an experimental stem-cell treatment developed by Baltimore's Osiris Therapeutics, which yesterday announced results of the 10-person clinical trial Gagne took part in.

...

"I have hopes, but I'll be very candid. I've been on other treatments as long as 13, 14, 15 months that worked reasonably well. The vote is still out on this," he said. "Right now, it's probably the best treatment that I've ever had based on the results that I've achieved, but [I'm waiting to see] if it works like this for, let's say, 15, 16, 24 months."

The Baltimore Sun has further details in their business section.

Prochymal, which Osiris says interacts with immune cells to reduce inflammation and aid tissue repair, already is in late-stage trials as a treatment for a rare inflammatory condition associated with bone marrow transplants. If approved, it would likely be the first pure stem cell product on the market.

What is Cimzia?

The last time I mentioned Cimzia it was so new that I couldn't find any information about how it actually worked. Now, that august journal of medical knowledge, BusinessWeek online, fills in the gaps, in an interesting interview with the CEO of Cimzia developer UCB, Roch Doliveaux:

BW: Analysts reckon Cimzia has blockbuster potential. What other Crohn's disease drugs are on the market, and how is Cimzia different?

RD: The biggest rivals are Remicade from Johnson & Johnson and Abbott's Humira, a drug currently approved for use in rheumatoid arthritis that's expected to gain additional approval for use in Crohn's.

Both of these drugs are monoclonal antibodies, which are derived from very large molecules. These drugs require a lengthy, complex, and expensive manufacturing process. Because they're large molecules, they tend to penetrate tissues poorly, so they must be administered by injection. Also, these larger antibodies can often trigger unwanted immune responses.

In contrast, Cimzia is the next generation of antibodies. We use the smallest possible fragment of an antibody, called a nanobody. As these nanobodies are much smaller, they're able to penetrate tissue in the body more easily. The big advantage with nanobodies, we believe, is that it requires a much simpler manufacturing process, which means that over time it will be a lot less expensive than monoclonal antibodies to produce.

The way Cimzia is administered is also unique. While Remicade is given by an intravenous infusion at the doctor's office or hospital, Cimzia is the first Crohn's drug that is able to be given by injection through the skin. It's similar to the way diabetics are able to self-inject insulin.

Of course, if they made it into a pill instead of an injection, they'd get an even more enthusiastic response. However, the ability to inject yourself at home is a massive advantage over endless visits to the doctor.