True To Its Cancer Focus, Medarex Outlicenses C. Diff Therapy To Merck

Medarex and partner Massachusetts Biologic Laboratories will split equally $60 million upfront and potential milestones worth $165 million.

Medarex signed a worldwide licensing agreement with Merck & Co. for its Phase II Clostridium difficile therapy, putting the biologic into the hands of a partner with the expertise and global reach to fully exploit the asset, Chris Schade, Medarex's chief financial officer, said April 21.

The deal garnered Princeton, N.J.-based Medarex and its partner, Massachusetts Biologic Laboratories, an upfront payment of $60 million, with future development and approval milestones worth another $165 million. All payments are to be divided equally between Medarex and MBL, which is affiliated with the University of Massachusetts Medical School. MBL is the only non-profit FDA-licensed manufacturer of vaccines and other biologic products in the U.S.

Medarex first teamed up with MBL in 2002, marrying the biotech's proprietary antibody platform with the academic group's expertise in infectious disease. Their first project explored a therapy to combat severe acute respiratory syndrome (SARS). Since then they've collaborated on other projects, but the goal with C. diff was to create a therapy that could simultaneously attack two different disease-causing toxins secreted by the bacteria.

The resulting cocktail, administered intravenously, contains an antibiotic and two monoclonal antibodies. The first antibody, MDX-066 or CDA-1, is aimed at toxin A, while the other antibody, MDX-1388 or CDB-1, is aimed at toxin B. The idea, said Schade, is not to compete with the standard of care antibiotics, which include metronidazole and Viropharma's version of vancomycin, Vancocin , but to use the antibodies to block the nasty toxins and then "sop up the bacteria," with the antibiotics.

The C. diff organism is normally found in the intestinal tract, but is kept in check by other naturally occurring gut flora. Patients who are hospitalized or reside at long-term care facilities are especially prone to the opportunistic infection, which can move in and damage the lining of the colon in addition to causing severe diarrhea when antibiotics administered for other illnesses upset that complex microbial balance. Treatment involves administering yet more antibiotics. Because the microbial environment of the GI tract still isn't healthy, relapse occurs in about 20 percent of cases. Medarex and MBL believe their non-antibiotic therapy can overcome that cycle.

Positive Phase II data set Medarex/MBL therapy up for partnering

The partners had strong proof of concept when a 200-patient Phase II study of CDA-1/CDB-1 reported out in November. The patients were randomized to receive either SOC plus placebo or SOC plus the experimental therapy. Top-line data showed the recurrence rate in the placebo-treated group exceeded 20 percent for patients following successful treatment with antibiotics, while patients in the treatment group had a 70 percent reduction in recurrence rate (p=0.0004). Full results from the trial will be presented June 2 at Digestive Disease Week in Chicago.

According to Schade, after those results were released, the phone started ringing. Medarex and MBL chose Merck as a development and commercialization partner for the therapy based on the financial terms, Merck's developmental capabilities, particularly when it comes to regulatory approval for these types of compounds, and the company's "very strong commercial execution capabilities."

For Medarex, the decision to outlicense CDA-1/CDB-1 reflects the biotech's desire to remain focused on its areas of expertise: oncology and inflammation. The biotech's lead product is ipilimumab, a fully human cytotoxic T-lymphocyte-associated antigen-4 antibody partnered with Bristol-Myers Squibb as a treatment for melanoma, prostate, lung and other cancers (¹ (Also see "Medarex/BMS Working To Shift Ipilimumab Trial Endpoint" - Pink Sheet, 15 Jul, 2008.)).

It's not clear whether Merck will continue to look for additional treatments for C. diff beyond the Medarex/MBL products. It might be interested in OPT-80, an oral first-in-class macrocyclic antibiotic developed by San Diego anti-infectives firm Optimer that currently is in pivotal trials. If the Phase III data show efficacy, OPT-80 will be the first new C. diff therapy in decades and could command a premium from payers. (² (Also see "Optimer Rides High After OPT-80 C. Diff Trial Success" - Pink Sheet, 12 Nov, 2008.)).

Last year OPT-80 aced a non-inferiority trial against vancomycin; results of a similar trial are expected in mid-2009 with an NDA filing to follow in short order. In the North American trial, in addition to proving effective against C. diff, with a 77.7 percent cure rate, the antibiotic had a low recurrence rate, 13.3 percent compared to 24 percent in the vancomycin group.

- Shirley Haley ([email protected])