By Jay W. Cormier –
On December 8, 2015, FDA issued a complex set of approvals for a unique product, Kanuma (sebelipase alfa). Kanuma is indicated for the treatment of a rare disease known as lysosomal acid lipase (LAL) deficiency. The list of distinguishing descriptors for the Kanuma application is lengthy: Kanuma received orphan product designation, received breakthrough therapy designation, was given priority review, and was granted a rare pediatric disease priority review voucher.
There is a lot to discuss about the Kanuma approval, and we will try to keep it high-level in the interest of our readers’ time. . .
Approval of Genetically Engineered Chickens
Kanuma is a biologic that is manufactured by chickens that express the biological product in its egg whites. Along with the Kanuma BLA approval, then, FDA’s Center for Veterinary Medicine also issued a new animal drug approval for the chickens that have been genetically engineered to produce the human protein in their eggs.
The “Kanuma Chickens” represent the third genetically engineered animal that FDA has approved via its new animal drug authorities. The first such approval was for a goat that produces a human biologic in its milk, which was approved in 2009 (see our post on the Atryn Goats here). The second was the genetically engineered AquAdvantage Salmon, which FDA approved last month for use as a food-producing animal (see our post on the salmon approval here). The Kanuma Chickens are the second CVM approval for an animal engineered to produce a pharmaceutical product, and the first approval of a genetically engineered chicken.
We note that although in 2014 FDA approved a biological product produced in genetically engineered rabbits (here), FDA did not issue a new animal drug approval for the animals. We assume that no animal approval was issued because the rabbits are neither produced nor housed in the United States (we note that this was the company’s argument to FDA regarding why it need not seek an animal drug approval for the rabbits – see here).
Priority Review Voucher
As we have analyzed previously (here), the value of a priority review voucher to a company fortunate enough to have one is escalating quickly. This represents the sixth such voucher granted by FDA, and the going price for the fourth voucher was $350 million.
Another interesting issue is that FDA granted the pediatric rare disease priority review voucher for a product that is intended to treat a rare disease, but one that affects both pediatric and adult populations, and one where the data supporting approval included studies in the adult population. Whether this is a one-off case or represents a loosening of how FDA limits the scope of what diseases are deemed to be “pediatric rare diseases” is yet to be seen.
Use of Historical Controls
As we have discussed with our readers previously (here), FDA’s views regarding the use and validity of historical controls has changed over time and is currently an area of increasing focus within FDA. One conclusion of recent FDA actions has been that FDA is moving away from accepting historical controls for registration, Phase 3, studies. But, the Kanuma approval relied heavily on historical controls for its pediatric indication. Before drawing too many conclusions about historical controls writ large, in the case of the pediatric form of LAL deficiency, pediatric cases almost always resulted in death by 24 months of age, whereas treated subjects survived. With that clear of a difference, the data is pretty compelling no matter your view on the validity of historical controls.