Ipilimumab

Ipilimumab

Monoclonal antibody
Type	Whole antibody
Source	Template:Infobox drug/mab source
Target	CTLA-4
Identifiers
CAS Number	477202-00-9
ATC code	none
Chemical data
Formula	C6742H9972N1732O2004S40
Molar mass	148634.914 g/mol[[]]

Ipilimumab (also known as MDX-010 or MDX-101) is a human monoclonal antibody being developed by Bristol-Myers Squibb. It is intended to be used as a drug to activate the immune system. Ipilimumab is undergoing clinical trials for the treatment of melanoma., non small cell lung cancer (NSCLC), small cell lung cancer (SCLC) and metastatic hormone-refractory prostate cancer.

Mechanism of action

Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that is believed to play a critical role in regulating natural immune responses. The absence or presence of CTLA-4 can augment or suppress the immune system's T-cell response in fighting disease. Ipilimumab is designed to block the activity of CTLA-4, thereby sustaining an active immune response in its attack on cancer cells.

Clinical trials

As of October 2007 there are two fully human anti CTLA-4 monoclonal antibodies in advanced clinical trials. Ipilimumab, which is an IgG1 isotype, and Tremelimumab (from Pfizer) which is an IgG2 isotype.

On December 10, 2007, Bristol-Myers Squibb and Medarex released the results of three studies on ipilimumab. The three studies tested 487 patients with advanced skin cancer. One of the three studies failed to meet its primary goal of shrinking tumors in at least 10.0% of the study's 155 patients. Side effects are often considered acceptable risks for cancer drugs given the severity of the disease, and ipilimumab is no exception. The medication caused rashes, diarrhea and hepatitis in a number of the patients being tested. Despite the weaker-than-anticipated results, the companies are still planning to meet with regulatory agencies to discuss moving ahead with the medication. They hope to submit a filing to the U.S. Food and Drug Administration seeking approval in the first half of 2008. Since patients suffering from extremely serious diseases like melanoma have so few treatment options, the companies believe that even the marginal success rate will be appealing to some.

As of September 2008, Medarex is performing a Phase I/II dose escalation clinical trial of ipilimumab in metastatic hormone-refractory prostate cancer (HRPC). As of 2009, some of the patients with advanced prostate cancer had their tumors drastically shrink, promoting further trials.

On 19 June 2009 the Mayo Clinic reported two prostate cancer patients involved in a Phase II study using MDX-010 therapy who had been told initially that their condition was inoperable but had their tumors shrunk by the drug such that operation was possible and are now cancer-free as a result. This press report however has been criticized as being somewhat inaccurate and entirely premature. The clinical trials are still at an early stage and are being run alongside other treatments - which could be the real explanation for the tumor shrinkage. It is far too early to say whether ipilimumab has made any difference at all.

On June 5, 2010 Reuters reported on a clinical trial presented at the American Society of Clinical Oncology. The study showed an improvement in median survival from 6 months to 10 in patients with advanced melanomas, over treatment with an experimental vaccine called GP-100 (total n=676). Additionally, one year survival was 25% in patients treated with the vaccine, versus 46% in those treated with ipilimumab, and 44% for those receiving both.

The Phase III clinical studies on the drug were controversial for the use of the unconventional method of using a control arm (as opposed to using a placebo or standard treatment). The study tested ipilimumab alone, ipilimumab with a vaccine (called gp100) and the vaccine alone. Patients had a higher survival rate with ipilimumab alone, however it is not fully clear whether the vaccine caused toxicity, which would make the drug perform better by comparison. Catherine Arnold, a Credit Suisse analyst, wrote in a research note that "The design of this ipi study had left us skeptical on the chances that it would be sufficient for approval, given the low dose and the use of the vaccine as a comparison.”

External links

• U.S. National Library of Medicine: Drug Information Portal - Ipilimumab

pl:Ipilimumab