First oral tablet for chemotherapy-induced diarrhea in dogs receives conditional FDA approval

Officials with the FDA have conditionally approved crofelemer delayed-release oral tablets (Canalevia-CA1; Jaguar Animal Health) for the treatment of chemotherapy-induced diarrhea in dogs. This novel drug is the first treatment to be approved for this condition.^1,2

"Diarrhea is a common side effect of chemotherapy in dogs, which can be so severe that cancer treatment must be halted. Chemotherapy drugs often have potential side effects, but, unlike in human medicine where patients may be willing to tolerate some discomfort in exchange for a potential cure, the primary purpose of cancer treatment in dogs and other pets is to extend survival without sacrificing quality of life and comfort," said Steven M. Solomon, DVM, MPH, director of the FDA's Center for Veterinary Medicine, in a prepared statement. "This new medication provides veterinarians and dog owners with another tool to help control the side effects of chemotherapy for dogs undergoing such treatment."

According to Jaguar Animal Health, crofelemer is a plant-based medicine extracted and purified from the red bark sap—or “dragon's blood"—of the medicinal Croton lechleri tree in the Amazon Rainforest. The company’s subsidiary, Napo Pharmaceuticals, has established a sustainable harvesting program, under fair trade practices, for crofelemer to ensure a high degree of quality, ecological integrity, and support for Indigenous communities.²

Crofelemer is approved for human use to treat noninfectious diarrhea in adults with HIV/AIDS who take antiretroviral therapy. In humans, crofelemer functions by inhibiting the secretion of chloride ions and water by intestinal epithelial cells, thereby normalizing the gastrointestinal tract. According to the FDA, it is thought that the drug functions similarly in dogs.¹

Crofelemer delayed-release tablets for dogs are available only by prescription and can be administered at home. This therapy received conditional approval through the FDA’s Minor Use/Minor Species pathway, which is an option for drugs intended for minor uses in major species such as dogs, cats, horses, cattle, pigs, turkeys and chickens; or for minor species. According to the FDA, an estimated 1% of dogs in the United States receive a diagnosis of malignant neoplasia (cancer) per year, and not all dogs that receive treatment suffer from chemotherapy-induced diarrhea. Therefore, the agency estimates the rate of occurrence of chemotherapy-induced diarrhea in dogs in the US to be fewer than 70,000 dogs, which qualifies it as a minor use in a major species.¹

In addition, the conditional approval allows an animal drug sponsor to legally market its product after demonstrating that the drug is safe and manufactured in accordance with full approval standards and that there is a reasonable expectation of the drug's effectiveness. The initial conditional approval is valid for 1 year with the potential for 4 annual renewals. During this time, the animal drug sponsor must demonstrate active progress toward proving substantial evidence of effectiveness for full approval. The animal drug sponsor has 5 years to obtain full approval after receiving conditional approval, or it will no longer be allowed to be marketed.¹

The reasonable expectation of effectiveness of crofelemer delayed-release tablets was established in a study with 24 dogs (12 treated and 12 control). A dog was considered a treatment success if its diarrhea resolved and didn't recur during the 3-day study. Resolution of diarrhea was defined as a fecal score of 1 (well-formed stool) or 2 (soft or very soft, moist stool that doesn't have a clear shape). On the third day, 75% of dogs in the treated group were treatment successes compared to 25% of dogs in the control group. Additionally, diarrhea had resolved by 48 hours in 33% of dogs in the treated group compared to none of the dogs in the control group.¹

Some of the most common adverse effects across the laboratory studies and field studies were abnormal feces (soft, watery, mucoid, discolored feces), decreased appetite and activity, and vomiting.¹ According to Jaguar Animal Health, managing adverse effects is imperative to maintaining successful cancer treatment. However, more than half of the US veterinarians who responded to a recent survey sponsored by the company reported that chemotherapy-induced diarrhea interferes with their patient's chemotherapy treatment plan.²

According to Lisa Conte, president and CEO of Jaguar Animal Health and parent of 2 Jack Russell Terriers, crofelemer delayed-release tablets fills a large gap in the canine cancer care field by providing relief to dogs with chemotherapy-induced diarrhea.²

"In a third-party survey of dog and cat owners, the majority of participants (58%) indicated that they believed that the benefits of chemotherapy did not counterbalance the impact of the potentially negative side effects which animals may experience during treatment,” said Conte. “[crofelemer delayed-release tablets] provide another option to address the comfort of dogs undergoing chemotherapy and supports the dog's ability to maintain control, which is important for maintaining a comfortable living environment in the family household."

According to the FDA, veterinarians should advise owners about the possible adverse effects before using the crofelemer delayed-release tablets. Additionally, the FDA is encouraging dog owners to work with their veterinary team to report any adverse events or effects potentially related to the use of any drug, including crofelemer delayed-release tablets.¹

References

1. FDA Conditionally Approves First Oral Tablet to Treat Chemotherapy-Induced Diarrhea in Dogs. FDA. December 21, 2021. Accessed December 21, 2021. https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-oral-tablet-treat-chemotherapy-induced-diarrhea-dogs
2. Jaguar Health announces FDA Conditional Approval of Canalevia-CA1 (crofelemer), the first and only treatment for chemotherapy-induced diarrhea (CID) in dogs to receive any type of approval from FDA. Jaguar Animal Health. December 21, 2021. Accessed December 21, 2021. https://jaguarhealth.gcs-web.com/news-releases/news-release-details/jaguar-health-announces-fda-conditional-approval-canalevia-ca1