Lev Pharmaceuticals, Inc. said the Blood Products Advisory Committee to the US Food and Drug Administration (FDA) voted unanimously that there is sufficient evidence of the safety and efficacy for the approval of Cinryze (C1 inhibitor) for the prophylactic treatment of hereditary angioedema (HAE), also known as C1 inhibitor deficiency.
If approved, Cinryze would be the first C1 inhibitor replacement therapy for patients with HAE in the US. HAE is characterized by extremely painful, debilitating and sometimes fatal swelling of the extremities, face, genitals, abdomen and laryngeal tract. These attacks, which affect an estimated 10,000 people in the US, are usually unpredictable and may be spontaneous or precipitated by emotional or physical stress.
"The advisory committee's support of Cinryze represents an important advancement for HAE patients, caregivers, advocates and physicians who treat this devastating disease," said Joshua Schein, chief executive officer, Lev. "We look forward to continuing to work with FDA to secure approval of Cinryze in order to serve the patients and families who suffer from HAE".
The FDA had issued a complete response letter in January, in which the FDA requested information with respect to chemistry, manufacturing, and controls (CMC), as well as additional analyses of existing efficacy data from the Cinryze trials. No additional safety information and no additional clinical trials were requested in the FDA's letter. Lev subsequently filed its complete response to the FDA.
The FDA will review the advisory committee's recommendations in connection with its consideration of Lev's BLA.
Cinryze is a plasma-derived C1 inhibitor product that has been studied for the prophylactic and acute treatment of HAE. C1 inhibitor has been used for more than 35 years in Europe to treat patients with C1 inhibitor deficiency.
In the phase III prophylactic treatment trial, Cinryze decreased the normalized number of HAE attacks compared to placebo. The trial had a crossover design with 22 subjects in the efficacy data set. The difference between the number of angioedema attacks during treatment with Cinryze and the number during treatment with placebo was statistically significant (p less than 0.0001). During 12 weeks of prophylactic treatment with Cinryze, the number of attacks per patient ranged from 0 to 17.6 with a mean of 6.3 and a median of 6 attacks. During 12 weeks of treatment with placebo, the number of attacks per patient ranged from 6 to 20.5 with a mean of 12.7 and a median of 13.5 attacks. The clinically and statistically significant results for the primary endpoint demonstrating the efficacy of Cinryze were supported by statistically significant and clinically meaningful differences in all of the secondary endpoints, with Cinryze demonstrating reductions in the severity and duration of attacks, number of days of swelling, and need for open-label Cinryze rescue therapy.
In the phase III acute treatment trial, the median time to the onset of unequivocal relief of symptoms for an acute attack was significantly different between the Cinryze group and placebo group (greater than 4 hr). The application for the treatment of acute attacks of HAE was not presented before the Blood Products Advisory Committee and is currently under active review at FDA.
Additionally, Cinryze has been well tolerated with an adverse event profile no different from placebo. The most common adverse reactions observed have been upper respiratory infection and sinusitis. No drug-related serious adverse events (SAEs), no immunogenicity and no decrease in efficacy have been observed.