Aduro Biotech Drops After Quietly Disclosing Patient in Top Phase II Program Developed Serious Infection
Published: Nov 30, 2015
November 24, 2015
By Alex Keown, BioSpace.com Breaking News Staff
BERKELEY, Calif. – Aduro Biotech ’s dropped more than 14 percent Tuesday afternoon after it quietly reported a trial patient taking an experimental engineered-bacterial pancreatic cancer treatment developed a serious infection related to the medication.
California-based Aduro is developing cancer treatment that is a combination of GVAX pancreas and CRS-207, an immunotherapy using and engineered listeria bacteria to target cancerous cells and induce an immune response. The company noted that the combination treatment can cause some adverse side effects, including the development of lymphopenia. Some patients in a Phase IIa clinical trial did come down with the illness, but the company also noted one patient developed a more serious infection. Buried on page 31 of a filing to the U.S. Securities and Exchange Commission is a one-paragraph report of the patient being diagnosed with Listeria monocytogenes. The company said the event was diagnosed by the treating investigator as a case of listeriosis.
“With respect to this event, our understanding is that, in violation of the protocol, the patient’s central line port had been accessed during infusion of CRS-207 being given through a separate line. Several weeks after the CRS-207 infusion, the patient developed symptoms suggestive of an infection; therefore, per institutional practice, urine, stool and blood samples (from both the patient’s central line port site and from a peripheral vein) were collected. The blood culture from the port site was positive for Listeria monocytogenes, and was determined subsequently to be CRS-207 while all other cultures, including from the peripheral vein, were negative,” Aduro said in its filing.
Since the diagnosis, the company said the patient was administered intravenous antibiotics to fight the infection. After the round of antibiotics, follow-up cultures taken from both port and peripheral vein of blood as well as samples of sputum, stool and urine were negative for Listeria. At the request of the patient and the investigator, this patient continues to receive study treatment, the company said in its filing.
Despite the report of infection, Aduro said it will continue to run all clinical trials as planned. The company will hold a conference call on Nov. 25 at 7 a.m. Eastern Time to discuss the report and other matters.
In its filing, Aduro said the infection was treated as a Grade 3 on the U.S. Food and Drug Administration (FDA)’s toxicity grading scale. Grade 3 is considered severe, while Grade 4 is life-threatening and Grade 5 is death.
In the filing, Aduro noted that undesirable side effects attributed to the company’s therapies could “cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or comparable foreign regulatory authorities.”
In October, the FDA placed a hold on Advaxis 's experimental cancer treatment axalimogene filolisbac following the death of a patient. Like Aduro’s combination treatment, Advaxis’ therapy uses listeria to help trigger the body’s immune system to fight the cancerous cells. The Advaxis’ trial patient was hospitalized and treated for Listeria monocytogenes two years after taking axalimogene filolisbac as part of an investigator-initiated trial in 2013. In a statement, Advaxis maintains the patient’s death was a result of the severity of her cancer and not due to the company’s experimental cancer treatment. It is seeking proof from the FDA that the drug was not a factor in the death.
On Monday, Aduro Biotech announced the European Medicines Agency (EMA) granted Orphan Drug Designation to CRS-207 for the treatment of malignant pleural mesothelioma (MPM). Company stock is currently trading at $27.33 per share.