Humira released in USA

As expected, the new biologic medicine Humira has been approved by the FDA for adult use. According to the Wikipedia it may come in preloaded pen devices , which do sound like an improvement on the old manual syringe.

The story appeared in the Chicago Tribune's business pages:

"Humira has been shown to reduce signs and symptoms, and to induce and maintain clinical remission of Crohn's disease in patients who have had an inadequate response to conventional therapy, and in those patients who did not benefit from treatment, or who were intolerant to previous treatment with Remicade therapy," said Dr. Douglas Throckmorton, deputy director of the FDA's Center for Drug Evaluation and Research.

Abbott's drug also could be more convenient, the company and analysts say. Unlike Remicade, which has to be infused by a physician in the doctor's office, Humira is the only new Crohn's treatment that can be injected by the patient on his own.

Better surgery for Crohn's

Newswise has an excerpt from an article in the Journal of Surgery which contains interesting research into the long-term success of surgery that avoids removing parts of the bowel.

Among other findings, the study supports the notion that strictureplasty -- a bowel-sparing surgical procedure commonly used to correct Crohn's-related strictures -- is less likely to lead to stricture recurrence later on, compared to surgical excision ("resection") of the stricture.

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In decades past, Crohn's patients typically underwent surgical removal of the bowel at the point of stricture, although in recent years, corrective, bowel-sparing "strictureplasties" have become much more common. Dr. Michelassi has been a pioneer in developing new strictureplasty techniques. But he says that, up till now, surgeons lacked good information on the long-term consequences of these operations compared with resection.

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The study also found that up to a third of recurrences occur away from the site of the original operation. Furthermore, the type and site of prior surgery appears to influence the pattern of recurrence, the researchers found. The study also provides new guidance on what surgeons call "prophylactic strictureplasty" -- procedures aimed at preventing stricture-related trouble.

"Sometimes we encounter a stricture that isn't giving the Crohn's patient any symptoms right now. We know, though, that these strictures can lead to trouble in about 25 percent of cases," Dr. Michelassi explains. "Based on our findings, we would now advise that if an asymptomatic stricture can be fixed using bowel-sparing strictureplasty, then the surgeon should go ahead and perform that type of prophylactic procedure," the NewYork-Presbyterian/Weill Cornell expert says. "However, if fixing the problem requires bowel resection, then we would advise leaving the stricture alone, because there's still a 75 percent chance it will not cause the patient any harm."

Humira nears US release for Crohn's

The Boston Globe has an update on new medication that is expected to be released to US consumers soon. Crohn's afflicted people outside the US will probably welcome this news, as it will introduce a large new population for the drugs to be tested on. It'll be interesting to see if Humira lives up to its promise of providing longer-term remission than infliximab (Remicade).

Within days, Illinois-based Abbott Laboratories expects to win federal approval to sell its drug, Humira , currently used to treat rheumatoid arthritis, psoriatic arthritis, and a disease that causes arthritis of the spine, to combat the intestinal disorder.

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In clinical trials, 21 percent of patients who had stopped responding to Remicade were coaxed into remission by week four on Humira, compared with 7 percent who achieved remission on a placebo. Those results were impressive enough for the FDA to speed its handling of the drug -- trimming the review from 10 months to six months and indicating that an approval decision could come by the end of February.

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.
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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.
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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.
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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.

Vaccine hope

The Scotsman has a very optimistic article about a Crohn's vaccine that seems to work in mice:

John Hermon-Taylor, professor of surgery at St George's Hospital in London, believes he has made the breakthrough that could spell the end of the incapacitating disease.

Prof Hermon-Taylor has conducted pre-clinical vaccine tests on mice and says preliminary results returned no signs of side-effects or adverse reactions.

He said: "The vaccine proved highly successful in both treatment and prevention in pre-clinical trials.

Lest everyone gets their hopes up too high, as far as I'm aware, the theory on which this vaccine is based, stated in the article as fact, is still unproven:

Crohn's is a severe inflammation of the small intestine and the colon that can require surgery. It is caused by the bug MAP (Mycobacterium avium subspecies paratuberculosis), which is widely carried and contracted by farm animals.

Still, I have my fingers crossed that vaccine is a success in humans.

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.

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"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.