On May 1, 2023, the US Food and Drug Administration (FDA) conditionally approved Varenzin-CA1 (molidustat oral suspension) for the control of nonregenerative anemia associated with chronic kidney disease in cats.

While previous treatment options were limited to blood transfusions, exogenous erythropoietin administration, and iron supplements, this new drug helps increase the production of endogenous erythropoietin in feline kidneys. It is given to cats by mouth once daily for up to 28 days and may be repeated as needed after pausing treatment for at least seven days.

But something else makes it newsworthy: Varenzin-CA1 is the first drug for cats to be approved under the FDA’s new expanded conditional approval (XCA) policy. This will allow cats who are “suffering from the disease to receive treatment while the full effectiveness data is being collected,” said the FDA.

To understand more about the implications of the expanded conditional approval program, NEWSTAT spoke with Elizabeth Luddy, DVM, deputy director of the Office of New Animal Drug Approval at the FDA Center for Veterinary Medicine.

Luddy said that in July 2021, the FDA issued final Guidance for Industry (GFI) #261, Eligibility Criteria for Expanded Conditional Approval of New Animal Drugs, which expanded the conditional approval authority of the FDA to approve new animal drugs for “certain diseases or conditions that would not be eligible for conditional approval under the Minor Use/Minor Species Provisions of the Food, Drug, and Cosmetic Act.”

Drugs that now may be eligible for conditional approval under GFI #261 include those that treat “serious or life-threatening diseases or conditions” and those that address an “unmet animal or human health need,” but that are also “complex or particularly difficult to study.”

What is expanded conditional approval (XCA)?

XCA can be granted for drugs intended to treat major species (horses, cattle, pigs, dogs, cats, chickens, and turkeys). Initial approval is for one year, with the possibility of renewal four more times up to a maximum of five years.

If the drug has not been fully approved by the five-year mark, it can no longer be marketed or sold. Luddy reports that the XCA is an alternative pathway that allows “needed animal drugs to be legally available in a faster timeframe than a full approval, while also ensuring that the drug is safe and has a reasonable expectation of effectiveness when used according to the label.”

The safety requirement is the same between full FDA approval and XCA. The effectiveness requirement, however, is not. While full approval requires the manufacturer to provide “substantial evidence” of the drug’s efficacy, XCA requires only a “reasonable expectation of effectiveness.”

Manufacturers who apply to renew their XCA annually must provide evidence that they are progressing toward demonstrating “full effectiveness” with each renewal, Luddy said, and the FDA works with them to make sure their efficacy studies are appropriately designed. In the cases where the drug sponsor cannot demonstrate continued progress toward full effectiveness, the FDA may not renew the conditional approval.

Reduce, replace, and refine the use of animals in research

Apart from Varenzin-CA1, other drugs that are conditionally approved through XCA include:

• KBroVet-CA1 for seizure control in dogs,
• Panoquell-CA1 for treatment of pancreatitis in dogs, and
• Vetmedin-CA1 to delay the onset of congestive heart failure in dogs (Vetmedin is fully approved for the management of signs of congestive heart failure, but not for the delay of onset of congestive heart failure).

KBroVet-CA1 has an interesting and unique conditional approval story. Potassium bromide has been used off-label for the treatment of seizures in dogs for many years, but it had never been evaluated by the FDA for approval until recently.

The manufacturer of KBroVet-CA1 used a literature review conducted by the FDA that included 111 studies and their safety data in lieu of performing their own studies. The FDA describes this approach as “innovative” and fitting with the FDA’s commitment to “reduce, replace, and refine the use of animals in research.”

It's important to note that the FDA does not allow for extra-label or off-label use of conditionally approved animal drugs. Luddy said, “Veterinarians can only prescribe these drugs for the labeled uses.”

This program will stop taking new applications on October 1, 2028, Luddy said, but she hopes to see manufacturers “bringing forward the kind of innovative and novel products that the program was designed to elicit.”

Further reading

FDA Conditionally Approves First Drug for Anemia in Cats with Chronic Kidney Disease:
https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-drug-anemia-cats-chronic-kidney-disease

FDA Conditionally Approves First Drug to Delay Onset of Congestive Heart Failure in Dogs:
https://www.fda.gov/animal-veterinary/cvm-updates/fda-conditionally-approves-first-drug-delay-onset-congestive-heart-failure-dogs

FDA Grants First Conditional Approval Under Expanded Authority to Control Seizures in Dogs with Idiopathic Epilepsy:
https://www.fda.gov/news-events/press-announcements/fda-grants-first-conditional-approval-under-expanded-authority-control-seizures-dogs-idiopathic

FDA Conditionally Approves First Drug to Manage Acute Onset of Pancreatitis in Dogs:
https://www.fda.gov/news-events/press-announcements/fda-conditionally-approves-first-drug-manage-acute-onset-pancreatitis-dogs

Emily Singler, VMD, is a 2001 graduate of Penn State University and a 2005 graduate of University of Pennsylvania School of Veterinary Medicine. She has worked in shelter medicine, private practice, and as a relief veterinarian. She currently works as a veterinary writer and consultant and has her own blog, www.vetmedbaby.com.  

Photo credit: © loongar E+ via Getty Images Plus

Disclaimer: The views expressed, and topics discussed, in any NEWStat column or article are intended to inform, educate, or entertain, and do not represent an official position by the American Animal Hospital Association (AAHA) or its Board of Directors.