Date: 2012-09-27
Type of information:
phase: 3
Announcement: completion of the study
Company: Pharming (The Netherlands) Santarus (USA)
Product: Ruconest® (Rhucin® in non-European territories - conestat alfa)
Action
mechanism: Ruconest®/Rhucin® is a recombinant version of the human protein C1 inhibitor (C1INH). This protein naturally occurs in the human body. It belongs to the class of serine-protease inhibitors or serpins. It regulates several inflammatory pathways in the body by inhibiting certain proteins (proteases) that are part of the human defense system. Deficiency of functional C1 inhibitor leads to excessive activation of the complement system and other immunological and haemostatic pathways, giving cause to angioedema attacks. These attacks are characterized by acute and painful swellings of soft tissues. Administration of C1 inhibitor protein can normalize the immune response and stop the angioedemic attacks.
Disease: acute attacks of angioedema in patients with Hereditary Angioedema (HAE)
Therapeutic area: Genetic diseases - Rare diseases
Country: USA
Trial
details: Pharming conducted Study 1310 with Ruconest® under a Special Protocol Assessment (SPA) agreement with the FDA, and the study is intended to support the submission of a BLA in the U.S.
In Study 1310, Ruconest® was evaluated for the treatment of acute attacks of angioedema in patients with HAE in an international, multicenter, randomized, placebo-controlled Phase III study comparing a single IV infusion of 50 U/kg of Ruconest® to a saline control with a primary endpoint of time to beginning of symptom relief. The time to beginning of symptom relief was defined as the time lapsed from the beginning of the infusion of study medication to the beginning of a persistent beneficial effect based on the patient’s responses to a Treatment Effect Questionnaire for the primary attack location.
A 90 day follow-up period was required for each patient enrolled, or until such time that the patient required open-label treatment for a subsequent attack during the 90 day period. The data from the open-label extension are being collected for additional efficacy and safety analyses. The study enrolled a total of 75 patients who were randomized 3:2 to receive either Ruconest® or saline.
Latest
news: * On September 27, 2012, Pharming has announced that it has completed the clinical phase of the US pivotal Phase III clinical study (Study 1310) evaluating the investigational drug Ruconest® (recombinant human C1 inhibitor) for the treatment of acute attacks of angioedema in patients with Hereditary Angioedema (HAE). All 75 randomized patients have now reached the final time points according to protocol. Over the coming weeks, the trial database will be finalized and locked. The results will be analyzed and subsequently announced. Positive results of the study will trigger a US$ 10 million milestone payment to Pharming from its US partner Santarus Inc.
* On September 5, 2012, Pharming has announced that it has called the second tranche of 16,000,000 shares under the €10 million equity working capital facility previously announced on August 1, 2012. Alongside, Pharming has reported that the pivotal Phase III Study (Study 1310) of Ruconest® is now entering its last weeks prior to completion, with 71 out of 75 patients either treated for a subsequent attack of HAE or reaching the Day 90 endpoint of the study.
* On July 5, 2012, Pharming has announced that it has reached full recruitment of its ongoing US pivotal Phase III clinical study (Study 1310) evaluating the investigational drug Ruconest® (recombinant human C1 inhibitor) for the treatment of acute attacks of angioedema in patients with Hereditary Angioedema (HAE). 75 randomized patients are in the study and no further patients will be entered.
Study 1310 will now continue until such time that either all of the treated patients have received an open label treatment for a subsequent HAE attack, or until 90 days have lapsed since their randomized attack. This will be followed by the analysis of the results. Positive results of the study will trigger a US$ 10 million m ilestone payment to Pharming from its US partner Santarus Inc.
Currently 53 of the 75 patients have experienced a repeat attack or achieved a 90 day attack free period.
* On June 15, 2012, Pharming has provided an update on study 1310. Recruitment for this US pivotal trial for Ruconest® is ongoing (70 of the 75 patients required for the completion of study 1310 have been treated. ) and it is expected that full enrollment could be achieved within the next few weeks, in line with expectations. However, the company has announced that an internal oversight could potentially delay the unblinding of the top-line data by up to three months in order to complete the statistical package required by the FDA. This matter is currently being investigated.
The potential delay relates to the final step to completion of the trial consists of an additional blinded follow up period of up to 90 days, depending on when patients experience a subsequent attack. Once the last patient has completed the blinded follow-up period (experienced an attack or reached the 90 day mark), the data base will be locked and data analysis will begin. Pharming\'s experience with this trial is that participating patients are typically having a subsequent attack significantly sooner than 90 days, which means that locking of the data base and top-line results would still become available in Q3, 2012, however if the last patient entering the trial takes the full 90 days then top line results will be in Q4 2012.
Pharming has also announced that it has engaged Roth Capital Partners and Nomura Code to assist it in exploring strategic alternatives which could include a merger, equity investment or sale. No decision has been made to enter into any specific transaction at this time and there is no certainty that Pharming will enter into a transaction in the future. This review will be accompanied by additional cost containment measures and the ongoing discussions on platform technology collaborations. The company expects to be able to update the market in Q3, 2012.
* On August 4, 2011, Pharming and Santarus have announced that they have reached agreement with the FDA on the design of a Phase III clinical study with Rhucin® under the Special Protocol Assessment (SPA) process that is intended to support the submission of a BLA. 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.
* On May 5th, 2011, Pharming has announced that following discussions with the FDA, Pharming and its U.S. commercialization partner, Santarus, Inc. have submitted an amendment to the protocol for the Rhucin® Phase III clinical study into which the first patient was enrolled in February 2011. Pharming still anticipates that the Phase III study will be completed within 12 to 18 months from its original initiation. Based on input from the FDA and from the FDA meeting minutes, Pharming and Santarus have submitted an amendment to the protocol, including an increase of the number of patients from 50 to approximately 75 and a modification to the manner in which the primary endpoint will be assessed. This modification eliminates the need for further validation of the visual analog scale.
* On February 2, 2011, Pharming Group and Santarus announced that Pharming has begun an international, multicenter, randomized, placebo-controlled Phase IIIb clinical study evaluating the investigational drug Rhucin® (recombinant human C1 inhibitor) for the treatment of acute attacks of angioedema in patients with Hereditary Angioedema (HAE). Pharming expects to enroll approximately 50 patients in the study which may provide additional data, if required by the FDA, in support of an approval for Rhucin® at the 50 U/kg dose. Data from the study will also be used to provide additional validation of the visual analog scale used in measuring the clinical effects of Rhucin®. The study is expected to be completed in 12 to 18 months. The safety and efficacy of Rhucin® for the treatment of HAE attacks were previously evaluated in two randomized placebo-controlled studies and four open label treatment studies. Both placebo-controlled clinical studies showed statistically significant and clinically relevant improvement in the primary endpoint of time to beginning of relief of symptoms at Rhucin® dosage strengths of 50 U/kg and 100 U/kg compared to placebo. Pharming submitted a Biologics License Application (BLA) for Rhucin® to the FDA in late December 2010. In total, the BLA dossier included nine clinical studies covering 714 administrations in 190 subjects.
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, Pharming is responsible for conducting and paying for the current clinical study with Rhucin® in the treatment of acute attacks of angioedema in patients with HAE.
