Clostridium difficile infection (CDI) is a dangerous disease affecting millions of people worldwide.
Studies show growing incidence and mortality rates.
Morphochem has set out to introduce an innovative intravenous therapy for CDI, based on a novel antibacterial: MCB3681.
We are truly excited about this opportunity to fill an unmet medical need and make a difference for CDI patients.
Moving forward with the clinical development of our compound, we are now headed for Phase 2 studies.
Are you interested in being part of this effort? Get in touch. We are currently exploring partnering options.
IND application submitted to U.S. FDA in May 2016.
Morphochem will be present at both the 2016 BIO International Convention in San Francisco and the 2016 ASM Microbe in Boston.
We look forward to meeting you there!
Clostridium difficile—also known as C. difficile or C. diff—is a rod-shaped, Gram-positive bacterium which can cause gastrointestinal infections. Transmitted through spores, the disease mainly affects people with weak immune systems. Key risk factors therefore include advanced age, hospitalization, and the intake of medicines that damage the gut flora, such as antibiotics.
Up to 40 percent of patients develop severe forms of CDI, manifested in colonic inflammation, fever, high white-blood-cell count, and/or impaired kidney function. Of this group, about one-fourth are admitted to intensive care and may undergo major surgery due to complications such as ileus (intestinal blockage), toxic megacolon (intestinal dilatation), colonic perforation, or refractory colitis. Usually referred to as “severe and complicated CDI”, these conditions can be fatal for patients as there is no effective cure.
Having identified CDI as a threat to public health with limited treatment options, the U.S. FDA has included C. diff in its list of pathogens where related therapies may be designated as Qualified Infectious Disease Products (QIDP) under the GAIN Act (GAIN: Generating Antibiotics Incentives Now).
Public U.S. statistics recently identified CDI as one of the primary causes of healthcare-associated infections, ranking even above MRSA. In 2011, almost half a million Americans were newly infected; over 29,000 patients died within 30 days of diagnosis—more than twice the number of annual deaths from HIV/AIDS.
Recurrences have tripled over the past decade, due to increased (mis-) use of antibiotics, the growing numbers of immunosuppressed and/or elderly patients, and the emergence of new, hypervirulent C. diff strains. The latter now account for over 50 percent of cases. At present, 20 to 30 percent of CDI patients in the U.S. and Europe are expected to relapse—an alarming development.
For 2021, experts forecast over 1.5 million CDI infections for the U.S. and Europe combined and even higher numbers for Asia. The threat to public health is clearly increasing.
As almost all available analyses have focused on inpatients, the total cost burden on the healthcare system is likely to be underestimated. After all, a sizeable part of it has yet to be quantified: Figures do not include patients discharged to long-term care, the numerous instances of CDI onset in long-term care facilities, recurrent episodes, and people treated in outpatient settings. Recurrences in particular are associated with excessive cost, mostly attributable to significantly extended hospital stays.
Most patients diagnosed with mild to moderate CDI are given oral antibiotics, such as metronidazole, vancomycin, and/or fidaxomicin. Dosages are usually increased when the disease reaches a severer stage. For patients experiencing aggressive complications—that is, one in every ten—there is presently no proven effective therapy. Major and life-changing surgery such as colectomy is often inevitable.
Our compound MCB3681 is targeted at this particular group. We are developing an intravenous therapy for severe CDI, which should lead to improved cure rates and a major improvement in patients‘ quality of life.
Severe CDI is typically associated with profuse watery diarrhea causing accelerated excretion of any orally administered drug. When the patient’s condition is further complicated by colonic dilation, blockage, perforation, or refractory inflammation, oral therapy tends to be ineffective or not feasible at all: Patients usually have difficulties swallowing, and even if the intake of tablets is possible, conditions such as ileus or toxic megacolon may slow or block the passage through the digestive system. As a result, sufficient concentrations of antibacterials in the intestine are difficult to achieve with oral medication.
Intravenous therapy, by contrast, is expected to transport the antibacterial through the blood stream and intestinal wall and/or through the biliary system into the gut, thereby providing better access to the site of infection as well as the extended drug exposure needed for efficacy. Only a few of the antibacterials currently known generate sufficiently high fecal concentrations after intravenous administration and are active against C. diff.
At present, two intravenous antibiotics are administered against severe CDI where oral treatment is impossible: IV metronidazole and tigecycline. Although both lack regulatory approval for CDI, they are listed as therapy options in the current treatment guidelines issued by professional associations. These recommendations, however, are based on weak and low-quality evidence—simply because there is very little data on effective treatment for severe and complicated CDI.
The fact that these intravenous therapies are recommended despite their lack of approval shows that 1) intravenous treatment is considered a necessity by the medical community, and 2) there is no better intravenous treatment available to date. In short, an efficacious, approved intravenous therapy for severe CDI will fill an unmet medical need.
Our compound MCB3681 is a small-molecule antibacterial of a new class. It is targeted at the intravenous therapy of severe CDI—the first to undergo clinical development and pursue regulatory approval in the United States and Europe.
In pre-clinical studies, MCB3681 has demonstrated remarkable Gram-positive antimicrobial activity. It was particularly effective against C. diff clinical isolates (N = 335), regardless of both their virulence—including hypervirulent NAP1—and their resistance to other antibacterials. We detected no cross-resistance to any established class of antibacterials. (See our Downloads and Links section for further details.)
Due to its narrow Gram-positive spectrum and favorable impact on the commensal flora, MCB3681 has the potential to target C. diff bacteria selectively and provide a cure for severely ill CDI patients.
We are presently preparing a Phase 2 study for intravenous administration of MCB3837, the prodrug of MCB3681, to patients diagnosed with severe CDI. The study is planned to start in the second half of 2016.
European authorities are considering similar supportive measures to accelerate the development of antibiotics addressing unmet medical needs.
*GAIN is short for Generating Antibiotics Incentives Now. The GAIN Act forms part of the Food and Drug Administration Safety and Innovation Act, FDASIA.
Morphochem is a clinical-stage pharmaceutical company located in Munich, Germany. We are a 100-percent subsidiary of Biovertis AG, which is headquartered in Vienna, Austria. Biovertis’s major shareholder is TVM Capital.
At Morphochem, we are committed to the development and commercialization of MCB3681, a compound that will provide the basis for an innovative intravenous therapy for severe Clostridium difficile infections. Our lean operations reflect our dedication to this purpose.
As outlined here, MCB3681 has the potential to solve an urgent medical problem and address a sizeable market.
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