Shire Regenerative Medicine Initiates Two Phase 2 Studies Evaluating SRM003 (VASCUGEL®) In Patients With End-Stage Renal Disease Undergoing Arteriovenous Access Creation For Hemodialysis

Shire plc (LSE: SHP, NASDAQ: SHPG) today announced enrollment of the first patients in two Phase 2 studies designed to evaluate the efficacy and safety of SRM003 (VASCUGEL) in improving Arteriovenous Fistula (AVF) maturation and AV Graft (AVG) patency to facilitate hemodialysis in patients with End Stage Renal Disease (ESRD).

ESRD is advanced and irreversible kidney disease, treated mainly by hemodialysis or kidney transplantation. It is estimated that each year, there are more than 570,000 patients with ESRD treated in the U.S. and more than 250,000 patients in the EU^i,ii.

“There are currently no approved therapies that directly target the underlying physiological processes associated with the failure of AV access sites in hemodialysis patients,” said Steven Steinberg, MD FACP, president of the California Institute of Renal Research and the coordinating investigator for both studies. “I am excited to be involved in testing the efficacy and safety of SRM003 and look forward to seeing the product’s potential for improving hemodialysis access in AVF and AVG patients with ESRD.”

The first study, AVF01-SRM003, will evaluate the efficacy and safety of SRM003 in improving the rate of AVF maturation and use in subjects with ESRD undergoing surgery for the creation of an AVF in the upper extremity to facilitate hemodialysis access.

The second study, AVG01-SRM003, will evaluate the efficacy and safety of SRM003 in extending the duration of primary patency after placement of an AVG in the upper extremity in subjects with ESRD.

These are multi-center, single-blind, randomized, controlled studies, and they will enroll approximately 200 adult subjects each in 50 U.S. sites. In both studies, each treatment group will include approximately 100 subjects who will receive either SRM003 (two or three SRM003 sponges placed at time of AVF or AVG surgery, respectively) or standard practice at participating sites.

It is hypothesized that when placed outside the blood vessel, the seeded SRM003 gelatin matrix containing endothelial cells can provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.

Shire obtained the rights to VASCUGEL (developed under Shire as SRM003) when it acquired substantially all the assets of Pervasis Therapeutics in April 2012. This acquisition also provided Shire with a new cell-based technology platform.

“Achieving these clinical milestones less than one year after we acquired VASCUGEL from Pervasis Therapeutics demonstrates our unique ability to leverage our competencies in advancing development-stage regenerative medicine therapies,” said Jeff Jonas, MD, President of Shire Regenerative Medicine.

Diabetes is the global leading cause of ESRD, and accounts for approximately 40% of patients with ESRD treated in the U.S.  The development of SRM003 as a treatment option for improving AV access to facilitate hemodialysis in patients with ESRD furthers the Company’s commitment to therapies to help patients with diabetes, which includes DERMAGRAFT^®, approved in the U.S., Canada, Mexico, Israel, and Malaysia for use in the treatment of diabetic foot ulcers greater than six weeks duration.

About SRM003

SRM003 is composed of allogenic human aortic endothelial cells cultured in a gelatin matrix, Gelfoam^®.  SRM003 is placed on the outside of the blood vessel at the arteriovenous (AV) access site during the surgical intervention for the treatment of vascular injury associated with the intervention. SRM003 has received Orphan Product and Fast Track designation from the U.S. Food and Drug Administration and Orphan Product designation from the European Medicines Agency.

About Arteriovenous (AV) Access for Hemodialysis

End-stage renal disease (ESRD) is an advanced and irreversible kidney disease, treated mainly by hemodialysis or kidney transplantation. It is estimated that each year, there are more than 570,000 patients with ESRD treated in the U.S. and more than 250,000 patients in the EU^i,ii. Approximately 70% of these patients receive hemodialysisi. Before patients can undergo hemodialysis, an arteriovenous (AV) access site must be created where blood can be removed, filtered and returned to the body. The majority of AV access is achieved through either an AV fistula, where the vein is connected directly to the artery, or an AV graft, where the vein and artery are connected via a synthetic tube. There are an estimated 100,000 AV fistulas and 60,000 AV grafts occurring annually in the U.S.^iii,iv  Unfortunately, complications following AV access procedures are common and can include infection, blood clots, and narrowing of the vessel, which frequently lead to AV access failure. An estimated 60% of AV grafts fail after one year, requiring a procedure to restore flow or to create another AV access site^v,vi.

About Dermagraft

Dermagraft is a cryopreserved human fibroblast-derived dermal substitute; it is composed of fibroblasts, extracellular matrix, and a bioabsorbable scaffold. Dermagraft is indicated for use in the treatment of full-thickness diabetic foot ulcers greater than six weeks duration, which extend through the dermis, but without tendon, muscle, joint capsule, or bone exposure. Dermagraft should be used in conjunction with standard wound care regimens and in patients that have adequate blood supply to the involved foot. Dermagraft is contraindicated for use in ulcers that have signs of clinical infection or in ulcers with sinus tracts. Dermagraft is contraindicated in patients with known hypersensitivity to bovine products, as it may contain trace amounts of bovine proteins from the manufacturing medium and storage solution.

 

For further information please contact:

Investor Relations
Eric Rojas
[email protected]
+1 781 482 0999

Sarah Elton-Farr
[email protected]
+44 1256 894157

Media
Jessica Mann (Corporate)
[email protected]
+44 1256 894 280

Katie Sweet (Regenerative Medicine)
[email protected]
+1 858 754 6761

 

NOTES TO EDITORS

Shire enables people with life-altering conditions to lead better lives.

Through our deep understanding of patients’ needs, we develop and provide healthcare in the areas of:

• Behavioral Health and Gastro Intestinal conditions
• Rare Diseases
• Regenerative Medicine

as well as other symptomatic conditions treated by specialist physicians.

We aspire to imagine and lead the future of healthcare, creating value for patients, physicians, policymakers, payors and our shareholders.

www.shire.com

 

FORWARD - LOOKING STATEMENTS - "SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995

Statements included in this announcement that are not historical facts are forward-looking statements. Forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, that:

• Shire’s products may not be a commercial success;
• revenues from ADDERALL XR are subject to generic erosion;
• the failure to obtain and maintain reimbursement, or an adequate level of reimbursement, by third-party payors in a timely manner for Shire's products may impact future revenues and earnings;
• Shire relies on a single source for manufacture of certain of its products and a disruption to the supply chain for those products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis;
• Shire uses third party manufacturers to manufacture many of its products and is reliant upon third party contractors for certain goods and services, and any inability of these third party manufacturers to manufacture products, or any failure of these third party contractors to provide these goods and services, in each case in accordance with its respective contractual obligations, could adversely affect Shire’s ability to manage its manufacturing processes or to operate its business;
• the development, approval and manufacturing of Shire’s products is subject to extensive oversight by various regulatory agencies and regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to significant delays, increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• the actions of certain customers could affect Shire 's ability to sell or market products profitably and fluctuations in buying or distribution patterns by such customers could adversely impact Shire’s revenues, financial conditions or results of operations;
• investigations or enforcement action by regulatory authorities or law enforcement agencies relating to Shire’s activities in the highly regulated markets in which it operates may result in the distraction of senior management, significant legal costs and the payment of substantial compensation or fines;
• adverse outcomes in legal matters and other disputes, including Shire’s ability to obtain, maintain, enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on Shire’s revenues, financial condition or results of operations;

and other risks and uncertainties detailed from time to time in Shire’s filings with the U.S. Securities and Exchange Commission, including its most recent Annual Report on Form 10-K.

 

ⁱ Policy Options for Kidney Health in Europe. European Kidney Health Alliance (http://www.era-edta.org/images/2012_EKHA-policy_paper.pdf)
ⁱⁱ 2011 United States Renal Data System Annual Data Report (http://www.usrds.org/2011/view/default.asp).
ⁱⁱⁱ Fistula First Breakthrough Initiative 2011 dashboard (http://www.fistulafirst.org/AboutFistulaFirst/FFBIData.aspx)
^iv National Kidney Foundation Kidney Disease Outcome Quality Initiative Guidelines (http://www.kidney.org/professionals/KDOQI/guideline_upHD_PD_VA/index.htm)
^v Dixon et al. DAC Study Group.Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med. 2009; 360: 2191-2201.
^vi Hayashi et al. Vascular access for hemodialysis. Nat ClinPractNephrol. 2006; 2: 504-513.

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