Optimer's Dificid positive in post-hoc Phase III analysis in cancer patients
This article was originally published in Scrip
A post-hoc analysis of two Phase III clinical trials for Optimer Pharmaceuticals' Dificid (fidaxomicin) tablets as a treatment for Clostridium difficile-associated diarrhoea (CDAD) in cancer patients found higher clinical cure rates, better sustained response and lower recurrence of the bacterial infection than in study subjects who took oral vancomycin.
The data were taken from two studies that included 153 cancer patients treated for at least eight days with the macrocyclic antibacterial (known as Dificlir in Europe) or vancomycin. Optimer presented the post-hoc findings at the 22nd European Congress of Clinical Microbiology and Infectious Diseases in London on 31 March.
"This data is highly supportive of our strategy and focus on subpopulations. In the case of oncology, our drug is superior across all endpoints of this disease. It will prove invaluable to patients and in reducing the cost and the burden of this disease," said Optimer president and CEO Pedro Lichtinger in an interview with Scrip.
Cancer patients in both studies - subgroups of Optimer's original Phase III clinical trials used to win US FDA approval in 2011 - had significantly lower CDAD cure and sustained response rates than patients without cancer. However, Dificid was five times more likely than vancomycin to produce a clinical response and three times more likely to show a sustained response, while patients treated with vancomycin were 2.6 times as likely to have a recurrence of the infection.
Dificid performed better than vancomycin across all of the studies' clinical endpoints: clinical response (97.3% vs 87.5%, 95% CI 1.07-23.98; p=0.041), sustained response (83.6% vs 61.3%, 95% CI 1.50-6.91; p=0.003) and disease recurrence (14.1% vs 30.0%, 95% CI 0.16-0.89; p=0.025).
"This is absolutely phenomenal for our drug. These are fragile patients where they don't have the immune system to help them out," Mr Lichtinger said.
Cancer patients treated with Dificid had similar cure, recurrence and sustained response rates as non-cancer patients, while cancer patients treated with vancomycin more often had worse outcomes than patients without cancer. The safety profile was similar for both drugs in cancer patients with CDAD, an infection that's often caused by broad spectrum antibiotics that disrupt gastrointestinal flora and allow C. difficile bacteria to flourish.
Infections caused by C. difficile and the resulting diarrhoea are particularly dangerous for cancer patients with immune systems weakened by chemotherapy or stem cell transplants, and who often have prolonged hospitalisations and exposure to antibiotics. Cancer patients with solid tumour or haematologic malignancies account for 16% of hospital CDAD cases, according to Optimer.
During a 5 December 2011 day of presentations to Optimer investors, Dr Roy Chemaly, director of infection control and the antimicrobial stewardship programme at the University of Texas MD Anderson Cancer Center and an associate professor of medicine, said that CDAD lengthens hospitalisations and prevents advanced cancer patients from receiving stem cell transplants and chemotherapy, because they cannot be treated until they are infection-free.
That's why it's important for cancer patients to have access to antibiotics that treat CDAD effectively and with a lower likelihood of recurrence, Dr Chemaly explained.
Dificid is approved to treat CDAD in the US and EU, but Optimer will seek US FDA approval for indications that include prophylactic use in certain sub-populations, such as cancer patients. The company is designing clinical trials to prophylactically treat patients undergoing bone marrow transplants, who incur $130,000 in additional health care costs in California when they contract C. difficile infections.
Astellas is Optimer's development and commercialisation partner in Europe. On 29 March, the two companies announced a new partnership in Japan that gave Optimer a $20 million upfront payment, up to $70 million in milestone payments and additional payments equivalent to royalties on future Dificid sales in Japan (scripintelligence.com, 30 March 2012).