The U.S. Food and Drug Administration approved Stelara (ustekinumab), a biologic product for adults who have a moderate to severe form of psoriasis.

Plaque psoriasis is an immune system disorder that results in the rapid overproduction of skin cells. About 6 million people in the United States have plaque psoriasis which is characterized by thickened patches of inflamed, red skin, often covered with silvery scales.

“This approval provides an alternative treatment for people with plaque psoriasis, which can cause significant physical discomfort from pain and itching and result in poor selfimage for people who are selfconscious about their appearance,” said Julie Beitz, M.D., director, Office of Drug Evaluation III, in the FDAs Center for Drug Evaluation and Research.

Stelara is a monoclonal antibody, a laboratoryproduced molecule that mimics the bodys own antibodies that are produced as part of the immune system. The biologic treats psoriasis by blocking the action of two proteins which contribute to the overproduction of skin cells and inflammation.

Three studies of 2,266 patients evaluated the biologics safety and effectiveness.

Since Stelara reduces the immune systems ability to fight infections, the product poses a risk of infection. Serious infections have been reported in patients receiving the product and some of them have lead to hospitalization. These infections were caused by viruses, fungi, or bacteria that have spread throughout the body. There may also be an increased risk of developing cancer.

The FDA is requiring a risk evaluation and mitigation strategy or REMS for Stelara that includes a communication plan targeted to healthcare providers and a medication guide for patients.

Stelara is manufactured by Centocor Ortho Biotech Inc. of Horsham, Pa., a whollyowned subsidiary of Johnson & Johnson of New Brunswick, N.J.

The Medicines Company (NASDAQ MDCO) announced the withdrawal of the European marketing authorization application (MAA) for the 200mg 37 day daily dose therapy of oritavancin, its investigational antibiotic drug candidate for the treatment of complicated skin and skin structure infections (cSSSI) caused by gram positive pathogens.

The MAA was filed in Europe in June 2008, by Targanta Therapeutics Corp. (Targanta). The Medicines Company acquired Targanta in February 2009. During their review of the MAA this year, the European Medicines Agency (EMEA) expressed concerns similar to those raised by the Food & Drug Administration (FDA) in their complete response letter, issued December 2008, to Targantas new drug application for oritavancin. Feedback from both agencies indicated that another trial would be required before approval could be considered. The Medicines Company has formally notified the EMEA of its decision to withdraw its MAA for the 200mg daily dose of oritavancin.

The Medicines Company is in dialogue with the FDA regarding plans for a global Phase 3 program. The Company also intends to confer with the European regulators to ascertain their support for the program design. As stated previously, the Company anticipates the start of the program in 4Q 2009, with an expected enrollment period of 12 years.

About Oritavancin

Oritavancin is an investigational, semisynthetic lipoglycopeptide antibiotic with potent and rapid bactericidal (killing) activity against a broad spectrum of grampositive bacteria, including methicillinresistant staphylococcus aureus (MRSA). The Medicines Company is developing an IV formulation of oritavancin for the treatment of complicated skin and skin structure infections caused by grampositive bacteria. Future indications for the IV formulation may include anthrax, bacteremia, and surgical prophylaxis. In addition, The Medicines Company is developing an oral formulation of oritavancin for the treatment of Clostridium difficile.

Source

Early results of a trial found that a new drug that targets a genetic mutation found in over half of melanoma cases and some other cancers caused tumors to shrink and patients to live around 6 months longer without their disease getting worse, including those whose cancer had spread to the liver, lung and bone.

The results of the phase I trial on the experimental drug PLX4032 were released earlier this week at the American Society of Clinical Oncology conference in Orlando, Florida. The drug is being developed by Roche and Plexxikon.

Principal investigator Dr Keith T Flaherty, assistant professor at the Abramson Cancer Center of the University of Pennsylvania, said that

“PLX4032 has shown both tumour shrinkage and delay in tumour progression in patients whose tumours harbour a BRAF mutation, as well as improved quality of life for symptomatic patients.”

“Seven years after BRAF mutations were first identified we have validation that this mutation is a cancer driver and therapeutic target,” he said, adding that he and his coinvestigators were very excited about this new development, especially for their melanoma patients for whom there are few treatment options.

The gene mutation also occurs in about 10 to 15 per cent of colorectal tumors and 8 per cent of other solid tumors, said the researchers.

The trial showed that patients treated with PLX4032 had a median progression free survival of at least six months, including those with advanced metastatic cancer that had spread to other organs such as liver, lungs and bone. Current treatments usually give patients with advanced stage melanoma about two months extra life before their disease progresses.

The researchers also found thatPLX4032 was well tolerated at therapeutic doses.
Nine mutationpositive melanoma patients showed partial responses and four mutationpositive melanoma patients showed minor responses.
Disease control lasted up to 14 months with continuous therapy, with many responding patients still receiving treatment.
A small group of patients without the BRAF mutation did not respond to treatment, and progressionfree survival was less than two months, consistent with historical data.
Drugrelated adverse events included rash and photosensitivity and were classified as mild in grade.Roche also reported that

“Serious adverse events, including diagnosis of cutaneous squamous cell carcinoma, were observed in some patients after chronic treatment; however the safety profile has been warranted favourable for this population and the trial authorised to proceed to the next stage of investigation.”

PLX4032 targets and destroys cancer cells that carry the BRAF mutation.

BRAF is a gene that plays an important role in cell growth and division. The mutation, however, leads to uncontrolled cell growth and division which then causes 60 per cent of melanomas, the most deadly form of skin cancer, and about 8 per cent of all solid tumors.

Roche told the press they expect the new drugs “potency and selectivity” will lead to a treatment that is “both effective and well tolerated”.

Roche and its partner Plexxikon are also working on a companion diagnostic that will help identify which patients have the BRAF mutation.

The companies are now planning the next stage bigger trials and a registration programme starting later this year.

If this goes well, they will launch a tissuebased companion diagnostic test, which the companies describe as “another step forward in personalising cancer treatment”.

The two companies want to extent the use of PLX4032 for other cancers that harbour the BRAF mutation, and they are also developing the companion diagnostic test to select patients for clinical trials and then later for treatment with the drug.

Malingnant melanoma is the most serious form of skin cancer and about 160,000 people worldwide every year are diagnosed with it.

It is treatable if caught early, but once it has spread to other organs, the patients prospects are not good. Fewer than 2 per cent of patients with systemic metastases live more than two years.

Roche said the results on the new drug represent not only a step forward in understanding how to treat malignant melanoma but they also represent

“A significant advance in the use of biomarkers and diagnostic tools and the potential benefits of tailoring cancer treatment to individual patients.”

“Phase I study of PLX4032 Proof of concept for V600E BRAF mutation as a therapeutic target in human cancer.”
ASCO Abstract #9000, presented Monday 1 June 2009.
J Clin Oncol 2715s, 2009 (suppl; abstr 9000)

Sources Roche, ASCO abstracts, Vanderbilt University.

Written by Catharine Paddock, PhD