Specialty biopharmaceutical company Santarus, Inc. and biotech company Pharming Group NV announced that they have reached agreement with the US Food and Drug Administration (FDA) on the design of a phase III clinical study with the investigational drug RHUCIN (recombinant human C1 inhibitor) under the Special Protocol Assessment (SPA) process that is intended to support the submission of a Biologics License Application (BLA).

RHUCIN is being evaluated for the treatment of acute attacks of angioedema in patients with Hereditary Angioedema (HAE) in an international, multi-centre, randomized, placebo-controlled phase III study at a dosage strength of 50 U/kg with a primary endpoint of time to beginning of relief of symptoms. The phase III study was initiated in February 2011, but the FDA subsequently requested modifications to the study protocol.

Following discussions with the FDA and implementation of the Agency's recommended changes to the study protocol, the FDA has confirmed that Pharming's proposed trial design, clinical endpoints and statistical analyses are acceptable to the FDA. As a result of the discussions with the FDA, the changes to the study design include, as previously announced, a modification to the way the primary endpoint will be assessed and an increase in the number of patients from 50 to approximately 75. The protocol will also be changed to allow the introduction of open-label doses of RHUCIN as a rescue medication. The study is still expected to be completed by the third quarter of 2012.

“We are pleased to have reached agreement with the FDA under an SPA on the protocol for the phase III clinical study to support a BLA for RHUCIN in the US. Over the past months we have continued to open additional investigational sites and to screen patients for eligibility who can now be randomized into the amended trial,” said Rienk Pijpstra, MD, MBA, chief medical officer at Pharming.

Santarus has licensed certain exclusive rights from Pharming to commercialize RHUCIN in North America for the treatment of acute attacks of HAE and other future indications. Under the terms of the license agreement, a $ 10 million milestone is payable to Pharming upon successful achievement of the primary endpoint of the phase III clinical study.

The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design of proposed protocols that are intended to form the basis for a BLA or New Drug Application (NDA). Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in all the data contained in the BLA or NDA submission.

RHUCIN (INN conestat alfa) is a recombinant version of the human protein C1 inhibitor (C1INH). RHUCIN is produced through Pharming's proprietary technology in milk of transgenic rabbits and in Europe is approved under the name RUCONEST for treatment of acute angioedema attacks in patients with HAE. RHUCIN has been granted orphan drug designation in the U.S. for the treatment of acute attacks of HAE, a genetic disorder in which the patient is deficient in or lacks a functional plasma protein C1 inhibitor, resulting in unpredictable and debilitating episodes of intense swelling of the extremities, face, trunk, genitals, abdomen and upper airway. The frequency and severity of HAE attacks vary and are most serious when they involve laryngeal edema, which can close the upper airway and cause death by asphyxiation. According to the U.S. Hereditary Angioedema Association, epidemiological estimates for HAE range from one in 10,000 to one in 50,000 individuals.