Baxalta's ADYNOVATE Meets Endpoints in Phase 3 Study of Hemophilia A Patients Under 12 Years of Age

- Topline results find no inhibitors to ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated], treatment were reported and nearly 73 percent of treated patients experienced zero joint bleeds

- ADYNOVATE approved for adults in November 2015, offers proven bleed prevention with a simple, twice-weekly dosing schedule

- These data will form the basis of a U.S. filing for a pediatric indication in early 2016

News provided by

Nektar Therapeutics

Dec 21, 2015, 08:26 ET

BANNOCKBURN, Ill., Dec. 21, 2015 /PRNewswire/ -- Baxalta Incorporated (NYSE: BXLT), a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, today announced initial results from a Phase 3 clinical trial of ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated], an extended circulating half-life recombinant Factor VIII (rFVIII) treatment for hemophilia A based on ADVATE [Antihemophilic Factor (Recombinant)]. ADYNOVATE was approved by the U.S. Food and Drug Administration (FDA) in November 2015 for use in adolescent and adult hemophilia patients (12 years and older) for on-demand treatment and control of bleeding, and prophylaxis to reduce the frequency of bleeding episodes.

The prospective, uncontrolled, open-label, multi-center Phase 3 study was designed to assess the safety and immunogenicity of ADYNOVATE. The study enrolled 73 previously-treated patients (PTPs) with severe hemophilia A younger than 12 years of age and assessed the treatment's hemostatic efficacy in prophylaxis and treatment of bleeding episodes. All participants received prophylactic ADYNOVATE treatment (median 1.9 infusions per week) and were followed for six months.

ADYNOVATE met its primary endpoint in the study, as no patients developed inhibitory antibodies to ADYNOVATE. In addition, no treatment-related serious adverse events were reported. More than 70 percent (72.7 percent) of patients had no joint bleeds while on treatment with ADYNOVATE and nearly 40 percent (37.9 percent) experienced zero bleeds. The median annualized bleeding rate (ABR) among patient participants treated with ADYNOVATE was 2.0 (range 0-49.8; mean ABR 3.0), which was comparable to the rates seen in the adult study.

"These initial efficacy and safety findings indicate a potentially valuable role for ADYNOVATE to treat pediatric patients with hemophilia A, with data consistent with what was reported in clinical studies among adult patients," said John Orloff, M.D., head of Research & Development and chief scientific officer, Baxalta. "We will continue to build evidence on the value of ADYNOVATE through our robust clinical development program, which will support additional global registrations in the coming years."

With the study results, the company plans to file for marketing authorization in Europe and aims to file for a pediatric indication in the U.S. in early 2016. ADYNOVATE is currently under regulatory review in Japan, Canada and Switzerland. Baxalta plans to present the complete data from this study at a congress in 2016.

In addition to an ongoing study in the surgical setting, Baxalta's continuation study remains ongoing to assess long-term safety and efficacy in PTPs with severe hemophilia A. The company has also recently announced the initiation of a study of previously-untreated patients (PUPs) with severe hemophilia A, as well as a study to evaluate pharmacokinetic (PK)-guided prophylaxis dosing with ADYNOVATE (the PROPEL study).

ADYNOVATE is built on the full-length ADVATE molecule, a leading treatment for hemophilia A that been used by patients worldwide for more than 12 years. Through a collaboration with Nektar Therapeutics (NASDAQ: NKTR), ADYNOVATE leverages proprietary PEGylation technology designed to extend the amount of FVIII available for use in the body. The technology was selected because it maintains the integrity of the parent molecule (ADVATE) and reduces the time at which the body clears ADYNOVATE, resulting in increased circulating half-life. This proprietary technology has been used for more than 15 years in a number of approved medicines that treat chronic or serious conditions.

About ADYNOVATE
ADYNOVATE, [Antihemophilic Factor (Recombinant), PEGylated], is a human antihemophilic factor indicated in adolescent and adult patients (12 years and older) with hemophilia A (congenital factor VIII deficiency) for:

On-demand treatment and control of bleeding episodes
Routine prophylaxis to reduce the frequency of bleeding episodes

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

Detailed Important Risk Information

CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies
Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS
Common adverse reactions (≥1% of subjects) reported in the clinical studies were headache and nausea.

For Full Prescribing Information, visit http://baxalta.com/assets/documents/ADYNOVATE_PI.pdf.

About ADVATE
ADVATE [Antihemophilic Factor (Recombinant)] is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

Control and prevention of bleeding episodes
Perioperative management
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

ADVATE is not indicated for the treatment of von Willebrand disease.

Detailed Important Risk Information

CONTRAINDICATIONS
ADVATE is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & PRECAUTIONS
Hypersensitivity Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting.

Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies
Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS
Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII.

The most common adverse reactions observed in clinical trials (frequency ≥5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

Please see full prescribing information for ADVATE at: http://www.baxalta.com/assets/documents/ADVATE_PI.pdf.

ADVATE has a demonstrated efficacy and safety profile for the treatment of hemophilia A. ADVATE is a full-length (derived from the complete FVIII gene) recombinant FVIII product that is processed without any blood-based additives. Because no blood-derived components are added at any stage of the manufacturing process, the potential risk of transmitting pathogens that may be carried in blood-based additives is virtually eliminated. There have been no confirmed reports of transmission of HIV, HBV or HCV with rFVIII treatments.

ADVATE is the world's most prescribed FVIII treatment. It is currently approved in 67 countries worldwide, including the United States, Canada, 28 countries in the European Union, Algeria, Argentina, Australia, Brazil, Brunei, Chile, China, Colombia, Ecuador, Hong Kong, Iceland, India, Iraq, Israel, Japan, Kuwait, Macau, Malaysia, Mexico, Morocco, New Zealand, Norway, Panama, Puerto Rico, Qatar, Russia, Saudi Arabia, Serbia, Singapore, South Korea, Suriname, Switzerland, Taiwan, Tunisia, Turkey, Ukraine, Uruguay, and Venezuela.

About Baxalta
Baxalta Incorporated (NYSE: BXLT) is a $6 billion global biopharmaceutical leader developing, manufacturing and commercializing therapies for orphan diseases and underserved conditions in hematology, oncology and immunology. Driven by passion to make a meaningful impact on patients' lives, Baxalta's broad and diverse pipeline includes biologics with novel mechanisms and advanced technology platforms such as gene therapy. The Baxalta Global Innovation and R&D Center is located in Cambridge, Massachusetts. Launched in 2015 following separation from Baxter International Inc, Baxalta's heritage in biopharmaceuticals spans decades. Baxalta's therapies are available in more than 100 countries and it has advanced biological manufacturing operations across 12 facilities, including state-of-the-art recombinant production and plasma fractionation. Headquartered in Northern Illinois, Baxalta employs 16,000 employees worldwide.

Forward-Looking Statements
This release includes forward-looking statements concerning ADYNOVATE, including expectations with regard to clinical trials, future regulatory actions and potential impact on patients. Such statements are made of the date that they were first issued and are based on current expectations, beliefs and assumptions of management.  Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond Baxalta's control and which could cause actual results to differ materially from those in the forward-looking statements, including the following: clinical trial results; satisfaction of regulatory and other requirements; actions of regulatory bodies and other governmental authorities; changes in laws and regulations; product quality, manufacturing or supply issues; patient safety issues; and other risks identified in Baxalta's filings with the Securities and Exchange Commission, all of which are available on Baxalta's website.  Baxalta expressly disclaims any intent or obligation to update these forward-looking statements except as required by law.