FDA Approves Removal of Boxed Warning From Regranex (Becaplermin) Gel, 0.01% as Multiple Studies Demonstrate Product Safety

Smith & Nephew (LSE:SN, NYSE:SNN), the global medical technology business, announces that the U.S. Food and Drug Administration (FDA) has approved the removal of the boxed warning regarding increased rate of mortality secondary to malignancy from the prescribing information of REGRANEX gel.

This decision is based on an evaluation of multiple post-market studies that demonstrated no increased safety risk with the use of REGRANEX gel.^1,2 The boxed warning was added to the REGRANEX gel label in 2008 following an initial retrospective study using medical claims database. Smith & Nephew submitted data to the FDA to petition for the removal of the boxed warning, they included results from an extension of the initial retrospective study and two additional postmarketing studies.

The three-year extension of the initial retrospective study observed that the additional mortality data attenuated the earlier safety signal. A retrospective study using medical claims from the Veteran Affairs health care database of patients without prior cancer evaluated 6,429 REGRANEX gel users compared to 6,429 patients without REGRANEX gel treatment over 11 years and provided substantial evidence for no increased incident cancer  or cancer mortality with REGRANEX gel use.

A second retrospective study using medical claims from the Veteran Affairs health care database of patients with prior cancer. The study evaluated patients with recently diagnosed malignancy in the prior one, two or three years before REGRANEX gel use compared to patients that did not receive REGRANEX gel over an 11-year study period. The rate of death due to cancer was similar in both groups and showed no evidence for increased risk of cancer death with the highest REGRANEX gel use.

REGRANEX gel is the first and only FDA-approved recombinant platelet-derived growth factor therapy for the treatment of lower extremity diabetic neuropathic ulcers. An estimated 15% of diabetics experience such diabetic foot ulcers in their lifetime. REGRANEX gel helps to heal these types of wounds an average of six weeks earlier than placebo gels, and is shown to provide a greater incidence of complete closure at 20 weeks compared to standard of care.²

The removal of the boxed warning from the REGRANEX label marks a milestone for the industry. This is the first time a single company successfully argued for the removal of a boxed warning, and the associated warnings within the label, based on clinical study findings and not requiring an advisory committee meeting. 

Mike Zagger, SVP Advanced Wound Management at Smith & Nephew, said:

“The clinical effectiveness of REGRANEX gel is well documented, and we are delighted that the FDA has now recognized the significant set of data in documenting its historical safety. This decision will reinforce, for both providers and patients, that REGRANEX gel is an appropriate first-line therapy for the treatment of lower extremity diabetic neuropathic ulcers and should be an integral part of any treatment regimen for this condition.”

REGRANEX gel is only available in the U.S.

REGRANEX gel is indicated for the treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply when used as an adjunct to, and not a substitute for, good ulcer care practices. The efficacy of REGRANEX gel has not been established for the treatment of pressure ulcers and venous stasis ulcers. The effects of REGRANEX gel on exposed joints, tendons, ligaments, and bone have not been established in humans. REGRANEX gel is a non-sterile, low bioburden preserved product. Therefore, it should not be used in wounds that close by primary intention. Malignancies distant from the site of application have been reported in both a clinical study and in postmarketing use. The benefits and risks of REGRANEX gel treatment should be carefully evaluated before prescribing in patients with known malignancy.

See complete prescribing information for more details.

Smith & Nephew is a global medical technology business dedicated to helping healthcare professionals improve people’s lives. With leadership positions in Orthopaedic Reconstruction, Advanced Wound Management, Sports Medicine and Trauma & Extremities, Smith & Nephew has around 15,000 employees and a presence in more than 100 countries. Annual sales in 2017 were almost $4.8 billion. Smith & Nephew is a member of the FTSE100 (LSE:SN, NYSE:SNN).

For more information about Smith & Nephew, please visit our website www.smith-nephew.com, follow @SmithNephewplc on Twitter or visit SmithNephewplc on Facebook.com.

To learn more about what we do to help reduce the human and economic cost of wounds,  visit www.closertozero.com.

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