Monoclonal Antibody Decoder

I've created a simple online tool, the MAB Decoder (see the top right of this page) to decode the generic name of any monoclonal antibody. For example, type in the common Crohn's medication infliximab to find from which animal species it is derived, and what part of the body it acts upon. This can be important because human-sourced antibodies are often better tolerated than those from other animals, which may influence your choice of medications. New monoclonal antibodies are being generated all the time, and often you'll see some new ones mentioned in passing. With this tool you simply enter their names to be able to learn more about them.

The MAB Decoder works with generic rather than brand names. Humira, for example, should be entered as adalimumab (the generic name of monoclonal antibodies always end in -mab). Incidentally, it is useful to be familiar with generic names because brand names may vary from country to country.

You can read more about monoclonal antibody naming at Wikipedia.

Although I created this tool to investigate Crohn's drugs, it will decipher monoclonal antibody names for all conditions. You can also try creating your own names, like humungofungomab!

October summary of biologics

Medscape [direct link requires subscription] has released a new summary of the latest findings in biologic therapy for Crohn's disease. Their previous summary on recent anti-TNF research was in June. Although that's still well worth reading, there have been much activity in this area since then.

This article discusses combination therapies, first-line therapy (i.e. should biologics be used earlier in the treatment regime), switching biologics if they become ineffective, safety and newer biologics which have only recently been approved for use. Most of these have been reported in detail previously, but it's handy to have them summarised in one place.

Post AntiTNF biologics

The most recent successfully-introduced medications for the treatment of Crohn's disease, infliximab and adalimumab, have targeted tumor necrosis factor (TNF). However, they are ineffective for some people, and become ineffective in others over time. The Lancet(free registration required) reports some of the different directions that researchers have been examining for further biologic agents, their safety and effectiveness in trials.

Investigators have long sought to identify a micro-organism that causes inflammatory bowel disease. The present theory suggests a breakdown in the balance
between putative species of protective versus harmful bacteria—a notion that has been termed dysbiosis.

Whilst many current drugs reduce the symptoms of Crohn's by suppressing the immune system, research is continuing into drugs that act as immune stimulators.

As a result of decades of intensive research, treatment for inflammatory bowel disease is undergoing a transition from the era of TNF antagonists to an era of novelbiological agents, including those that are able to stimulate the innate immune system.

As you might expect for a medical journal it's quite a technical article, but well worth the effort to see what possible treatments are just around the corner. For easier reading there's a summary at Medical News Today.

Summary of latest anti-TNF research

Medscape (free subscription, or go via Google) has a great in-depth interview with David A. Schwartz, Director of the IBD Center at Vanderbilt University Medical Center, about the latest developments in anti-TNF medications for the treatment of Crohn's Disease. He manages to translate medical-journalese into language that non-medical professionals can understand. It includes important information regarding safety and effectiveness of newer therapies.

Towards the end of the interview he indicates the method of delivery is one important factor in patients' preference for newer biologics over the original infliximab (noting that infliximab must be delivered intravenously by a medical professional, whereas other drugs can be administered by the patient themself at home):

100% of patients who had received both intravenous and subcutaneous anti-TNF therapy preferred the subcutaneous route. The main reasons given for this preference included that the infusions were painful as well as the autonomy that subcutaneous administration provided.

Tysabri approved for Crohn's in USA

Bloomberg.com reports that the Food and Drug Administration has approved Tysabri (Natalizumab) for treating Crohn's disease in some cases. Tysabri is already being used for the treatment of Multiple Sclerosis, but was briefly withdrawn after some serious side effects. European regulators refused to approve it for Crohn's disease.

Boston.com has further information:

European regulators recently rejected a similar request to use the drug as a Crohn's treatment, arguing the risk of infection outweighed the relatively modest benefit of Tysabri.

Biogen Idec temporarily shelved the drug three years ago after it was linked to a rare brain disease. The company says there have not been any additional cases of the disease since sales resumed in 2006, with new guidance on how it should be used. But some doctors remain wary of the treatment, even though it has been shown to be highly effective in some patients.

The Wikipedia has more comprehensive background on the drug.

How do Tysabri and Cimzia work?

The Los Angeles Times has a good description of how two of the latest Crohn's medications operate:

Cimzia is also a TNF blocker, but unlike the others it contains only part of the antibody -- the portion that recognizes TNF. The rest of the antibody -- the part that can induce its own immune response -- is replaced with a compound called PEG.

This PEG tail stabilizes the drug, allowing it to stay in the patient's body much longer[...].

That means patients would only require treatment every other month, as opposed to every other week with Humira.

During inflammation, infection-fighting white blood cells of the immune system cruise through capillaries, searching for infection. When tissues are infected, they put out signals to slow down the blood cells and coax them to enter the tissue. [...]

Tysabri binds to those exit signs -- blocking them from recognition by the immune cells that are causing the Crohn's. So the white blood cells keep on moving, and the course of inflammation is stopped.

It'll be exciting to see how well these drugs operate on a wider variety of Crohn's patients, if and when they are approved.

Recent developments

Hidden behind the subscription wall of The Wall Street Journal is a nice summary of the current status of the various Crohn's treatment options. That article has now made its way into the free world via the naplesnews.com.

Amongst developments not yet reported in this blog is news of medicine which is potentially better than the highly-regarded anti-TNFs gaining popularity today. These include arthritis drug Orencia, interleukin-12 and interleukin-23 (interleukin has been mentioned previously), and a drug using adult stem cells.

Besides anti-TNFs, there is a rheumatoid arthritis drug from Bristol-Myers Squibb, called Orencia, that is being studied for Crohn's disease. The drug works on inflammation earlier in the process than do anti-TNFs. Bristol started the final phase of human testing of Orencia against Crohn's last month and is currently enrolling patients in a trial.
...
J&J and Abbott are working on drugs that inhibit two proteins called interleukin-12 and interleukin-23. Both companies are in the middle stages of human testing. Strober, of the National Institute of Allergy and Infectious Diseases, says the benefit could be tackling inflammation much earlier in its development than the anti-TNFs do, but that the drugs could carry an increased risk of infection.
...
Osiris Therapeutics, based in Baltimore, just got approval from the FDA to go into the third and final phase of human testing on a Crohn's drug that uses adult stem cells. The company says the agency gave the drug fast-track status, which means it could come to market as early as 2008.

The drug is thought to work by correcting inflammation only where it's taking place — which could help avoid excessive immune suppression.

Natalizumab potential for Crohn's downplayed

The Boston Globe reports that it is unlikely that natalizumab (marketed as Tysabri) will be a viable treatment for Crohn's disease. Earlier reports had looked promising.

Biogen Idec's chief executive, James Mullen, says the Cambridge biotechnology company is unlikely to receive approval from European regulators to use its drug Tysabri to treat patients with Crohn's disease, a debilitating intestinal ailment.
...
In a comprehensive safety review last year, the companies found two multiple sclerosis patients with PML who were also being treated with Biogen Idec's drug Avonex, another treatment for multiple sclerosis. One of those patients survived. Another patient in a Crohn's trial, who died from PML, had been treated with immunosuppressants.

That pattern suggested the risks of contracting PML while using Tysabri could increase if a patient is also being given a drug that affects the immune system. If so, that raises the risks of treating Crohn's patients with Tysabri, because many have weakened immune systems.

"Against the backdrop of PML, where you have a set of patients that already get bombarded with immunosuppressants over 20 to 30 years, [Crohn's] is not the first place we'd go to develop Tysabri," said Mullen. He said the drug looks more promising as a treatment for Lupus and certain cancers.

CBC News has further details from a north American perspective:

Caroline Stewart, an industry analyst for Piper Jaffray, said it would be difficult for Biogen Idec and Elan to match sales of the leading Crohn's treatment, Johnson & Johnson's Remicade, given Tysabri's PML risk.

"I think the sales in Crohn's are going to be limited, because it's not a life-threatening disease, and the potential side effects of Tysabri are life-threatening," Stewart said.

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.