ProFibrix US Phase II Study with FibrocapsTM Meets All Primary and Secondary Endpoints

ProFibrix B.V., a leader in the development of innovative products for hemostasis, today announced that its U.S. multicenter Phase II clinical trial with Fibrocaps in spinal, peripheral vascular and general surgery resulted in a highly statistically significant reduction in mean time to hemostasis (TTH) and incidence of hemostasis at 3, 5 and 10 minutes, as compared to active control.

A total of 70 patients were enrolled in the company’s U.S., prospective, randomized, single-blind, controlled, multicenter Phase II study with lead product Fibrocaps for mild to moderate surgical bleeding. The US study results confirm the efficacy and safety results recently reported from the Dutch Phase II study in hepatic resection. Both studies demonstrate that Fibrocaps has a very good safety profile comparable to active control, along with rapid hemostatic activity across multiple surgical indications.

Dr. Neil Singla, one of the Principal Investigators of the US Phase II study, said: “The combined ease of use and efficacy of Fibrocaps in spinal and vascular surgery constitute a great leap forward in hemostasis in these surgical settings. These surgeries require optimal precision and thanks to the rapid time to hemostasis of Fibrocaps we can quickly and safely obtain a clear field of vision during these interventions.”

Jan Öhrström, CEO of ProFibrix said: “We are delighted that the positive results of the US Phase II study confirm the results from our European study reported in November 2011. In fact, the results of the two Phase II clinical trials have de-risked the Fibrocaps program substantially. We plan to initiate a pivotal Phase III trial in H1 2012, and target a BLA filing in 2013. Based on its strong and competitive properties, we believe that after launch Fibrocaps should be able to command a large share of the US$ 1 billion topical hemostat market.”

About Fibrocaps

Fibrocaps is a mixture of two essential blood clotting proteins, fibrinogen and thrombin, and is a unique dry powder topical fibrin sealant being developed to stop bleeding during or after surgery. Fibrocaps is clearly differentiated from existing liquid tissue sealants and hemostats: it is ready for immediate use, and is stable at room temperature.

About the Study

The Phase II clinical trial of Fibrocaps (FC-002 US) was a prospective, randomized (2:1), single-blind, controlled study in 70 subjects undergoing spinal (n=37), peripheral vascular (n=30) and general surgery (n=3). The study was conducted at 8 sites across the U.S. Fibrocaps was considered to have a very good safety profile, with no adverse events attributed to Fibrocaps, which is consistent with the previously conducted Phase II study. The primary efficacy endpoint of the study was a pooled intent-to-treat analysis of the mean TTH of Fibrocaps versus active control. The TTH means ± SD were 1.9 ± 1.3 min for Fibrocaps (n=47) and 4.8 ± 3.1 min for control (n=23) (p<0.001). The secondary endpoints of incidence of hemostasis at 10, 5 and 3 min were all statistically significant, with p-values of 0.003, 0.001 and <0.001, respectively.

ProFibrix conducted the Fibrocaps Phase II study in the U.S. under an open IND with the FDA. For more details on the study, please go to http://www.clinicaltrials.gov.

ProFibrix to present today at Biotech Showcase in San Francisco

ProFibrix will present at the Biotech Showcase 2012 in San Francisco, on Wednesday, Jan. 11, 2012. Jan Öhrström, CEO of ProFibrix, will make a formal presentation on the company at 9:45 a.m. in the Stockton Room. The Biotech Showcase runs parallel to the 30th Annual J.P. Morgan Healthcare Conference, and takes place at Parc 55 Wyndham San Francisco - Union Square.

About ProFibrix

ProFibrix (www.profibrix.com) was founded in 2004 and is headquartered in Leiden, The Netherlands, with a subsidiary in Seattle, WA, USA. The company leverages its expertise in fibrinogen technology to develop and bring to market innovative products for the hemostasis and regenerative medicine markets. Human fibrinogen plays a pivotal role in blood clotting and tissue healing. ProFibrix is led by a team with extensive commercial, clinical and scientific experience in the hemostasis field.

Hemostat Market Research Indicates Strong Growth

Source: Mediligence Blog

Transfusion Guidelines in Children Reviewed

December 29, 2011 — Thresholds for transfusing children vary from those in adults, according to a 2-part review study published in the January 2012 issue of Anaesthesia & Intensive Care Medicine.

"The transfusion of a blood product into a child is associated with a greater risk of harm when compared to an adult," writes Rachel Hartrey, MBBCh, FRCA, a consultant pediatric anesthetist at Southampton University Hospital National Health Service Trust in the United Kingdom. "The younger the child, the greater these risks are: 18:100,000 in all paediatric age groups, increasing to 37:100,000 in those less than 1 year of age; this compares to 13:100,000 in adults. These calculations are based on red cell transfusion alone and do not take into account risks posed by other blood products, in particular fresh frozen plasma...and platelets."

The first part of the review describes normal hematological ranges in infants and children, lower levels of hemoglobin that can be tolerated without undue risks, and how to evaluate blood loss to ensure that blood products are not transfused unnecessarily.

The second part of the review describes strategies to avoid transfusion of blood products, and which fluids to use instead, as well as recommendations regarding how much and which blood products to use when indicated to reduce adverse effects.

Normal hemoglobin values are highest at birth (14 - 24 g/dL), decreasing to 8 to 14 g/dL at 3 months, and then gradually increasing to 10 to 14 g/dL at age 6 months to 6 years, 11 to 16 g/dL at age 7 to 12 years, and 11.5 to 18 g/dL in adulthood.

Thresholds for Red Blood Cell Transfusions

For infants younger than 4 months, thresholds for red blood cell transfusions based on hemoglobin levels are 12 g/dL for preterm infants or term infants born anemic, 11 g/dL for chronic oxygen dependency, 12 to 14 g/dL for severe pulmonary disease, 7 g/dL for late anemia in a stable infant, and 12 g/dL for acute blood loss exceeding 10% of estimated blood volume.

For infants older than 4 months, thresholds for red blood cell transfusions based on hemoglobin levels are 7 g/dL in a stable infant, 7 to 8 g/dL in a critically unwell infant or child, 8 g/dL in an infant or child with perioperative bleeding, and 9 g/dL in an infant or child with cyanotic congenital heart disease (because of increased oxygen demand). To slow bone marrow stimulation in a child with thalassaemia major, the recommended threshold is 9 g/dL.

For a child with sickle cell disease (SCD), the recommended threshold is 7 to 9 g/dL, or more than 9 g/dL if the child has previously had a stroke. When a child with SCD undergoes major surgery, the threshold should be 9 to 11 g/dL, and sickle hemoglobin should be less than 30%, or less than 20% for thoracic or neurosurgery.

Strategies to Avoid Transfusion

Strategies to avoid perioperative transfusion of allogeneic blood include:

• maximizing preoperative hemoglobin;
• preoperative autologous donation, which is associated with risks including transfusing the wrong blood unit, wasting donated blood, bacterial contamination, and preoperative anemia;
• acute normovolemic hemodilution when major blood loss is expected;
• patient position to avoid increased venous pressure;
• use of tourniquets where appropriate;
• surgical technique to achieve hemostasis, using diathermy and tissue glues;
• deliberate hypotension (at a safe level);
• hypervolemic hemodilution, although infusing large volumes of fluid may dilute clotting factors and cause interstitial edema;
• use of tranexamic acid, although there is still uncertainty as to the most effective dose;
• and intraoperative cell salvage in operations in which major blood loss is anticipated. However, reactions to the retransfused blood have been reported, which may be caused by leukocyte stimulation or a reaction to the additives.

"Blood is not only involved in the carriage of oxygen, but has many other functions including haemostasis," Dr. Hartrey writes in the second part of the review. "Therefore it is little wonder that the development of a compound that deals with only one element of this (e.g. oxygen carriage) is compromised by side effects. Several of the proposed alternatives, including haemoglobin-based oxygen carriers...and fluorocarbon-based solutions, have been associated with significant clinical side effects such as abnormal clotting."

Dr. Hartrey has disclosed no relevant financial relationships.