Diabetic foot gel linked to increased cancer risk

NewsBot · Mar 27, 2008

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Reuters are reporting:
Cancer risk seen with J&J foot gel: FDA
Thu Mar 27, 2008 4:54pm EDT

A Johnson & Johnson foot gel used by diabetics may increase the risk of cancer and death, U.S. health officials said on Thursday in announcing an investigation into the issue.

The Food and Drug Administration said a study of the gel, called Regranex, found an increase in the number of cancer deaths among patients who had been prescribed the gel three or more times.

Regranex, approved for U.S. patients in 1997, is a prescription gel used to treat diabetic leg and foot wounds.

"At this time, FDA believes that there may be some evidence for an increased risk of death from cancer in patients who had repeated treatments with Regranex," the FDA said in a statement. "Because there are known risks associated with diabetic foot and leg ulcers that do not heal, the potential risk of using Regranex should be weighed against the benefit for each individual patient."

Barbara Montresor, a spokeswoman for Johnson & Johnson's Ethicon Inc unit that makes the gel, said the company was working with the agency and that Regranex is safe when used as directed.

Patients with diabetes -- a disease in which blood levels of sugar are too high -- are more susceptible to developing leg and foot wounds because they are less able to feel their feet.

Concern arose following a study of adult diabetes patients through an insurance plan database that found an increase in cancer deaths from January 1998 through June 2003. No single type of cancer was identified, the FDA said.

The agency did not say who conducted the study or how many patients were included, and an FDA spokeswoman declined to comment.

In an earlier study completed in 2001, more cancers were found in Regranex patients than in those who did not use the gel, the agency added.

Ethicon's Montresor did not immediately respond to a request seeking more details on the studies.

Shares of Johnson & Johnson closed down 8 cents at $64.62 on the New York Stock Exchange.
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Link to story

NewsBot · Mar 27, 2008

Here is the FDA statement on this:
Communication about an Ongoing Safety Review Regranex (becaplermin)

This information reflects FDA’s current analysis of available data concerning this drug. Posting this information does not mean that FDA has concluded there is a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising healthcare professionals to discontinue prescribing this product. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA has received information regarding a study that was performed to investigate the possibility of an increased risk of cancer in patients with diabetes who applied the product Regranex (a topical medicine) directly to their foot and leg ulcers. This study was done using a health insurance plan database of patients with diabetes who were at least 19 years of age or older, with no history of cancer and either prescribed Regranex or not. In this study, among those who were prescribed Regranex three or more times, there was an increase in the number of patients who died as a result of cancer. There was not enough information to say whether there was an increase in the number of patients that developed new cancers.

At this time, FDA believes that there may be some evidence for an increased risk of death from cancer in patients who had repeated treatments with Regranex. Because there are known risks associated with diabetic foot and leg ulcers that do not heal, the potential risk of using Regranex should be weighed against the benefit for each individual patient.

What does FDA know now about these data?
Regranex is a medicine that is a recombinant form of human platelet-derived growth factor which is applied directly to diabetic foot and leg ulcers that are not healing. The recombinant form of platelet growth factor has a biologic activity that is much like that produced naturally by the body. Growth factors cause cells to divide more rapidly. It is for this reason that the manufacturer continued to monitor studies begun before Regranex was approved in December 1997 for any evidence of adverse effects such as increased numbers of cancers. In a long term safety study completed in 2001, there were more cancers in people who used Regranex than in those who did not use it.

Following the report of the study completed in 2001, an additional study was performed using a health insurance database that covered the period from January, 1998 through June, 2003. This study used the database to identify two groups of patients with similar diagnoses, drug use, and use of health services, one of which used Regranex and one group that did not. The results of this study showed that deaths from cancer were higher for patients who were given three or more prescriptions for treatment with Regranex than those who were not treated with Regranex. No single type of cancer was identified, but rather deaths from all types of cancer, combined were observed.

This communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. FDA will communicate our conclusions, resulting recommendations and any regulatory actions to the public after the review of the data are completed.
The FDA urges healthcare professionals to promptly report serious and unexpected adverse reactions associated with Regranex to the FDA MedWatch reporting program, as described below.

online at www.fda.gov/medwatch/report.htm
by returning the postage-paid FDA form 3500 (available in PDF format at www.fda.gov/medwatch/getforms.htm) to 5600 Fishers Lane, Rockville, MD 20852-9787
faxing the form to 1-800-FDA-0178
by phone at 1-800-332-1088
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Admin2 · Mar 27, 2008

Related threads:
OASIS vs Regranex Gel
Press Release: Becaplermin Gel & Diabetic Ulcers

NewsBot · Apr 22, 2008

We initially missed this, here is the companies response to the FDA concerns from March 27:

Press Release:
BioMimetic Therapeutics Addresses FDA Communication on Regranex Safety Review

Franklin, Tenn. – March 27, 2008 - BioMimetic Therapeutics, Inc. (NASDAQ: BMTI) today addressed a communication the U.S. Food and Drug Administration ("FDA") released on its website this afternoon regarding the agency's ongoing safety review of Regranex®, a Johnson & Johnson product. Regranex is composed of recombinant human Platelet-Derived Growth Factor (rhPDGF-BB) (becaplermin) in a non-sterile ointment, which has been approved since 1997 for the chronic treatment of non-healing diabetic foot ulcers. The FDA communication specifically addresses Regranex use and does not address other rhPDGF-BB containing products. BioMimetic has not received any communications from the FDA related to today's web posting regarding Regranex.

The FDA communication provided information regarding a study that was performed to investigate the possibility of an increased risk of cancer in patients with diabetes who applied the product Regranex (a topical medicine) daily, directly to their dermal ulcers for up to 140 consecutive days. According to the communication, "posting this information does not mean that FDA has concluded a causal relationship between the drug product and the emerging safety issue. Nor does it mean that FDA is advising healthcare professionals to discontinue prescribing this product."

In the study referenced in the FDA communication and highlighted below, there appeared to be inconsistent data. One analysis indicated no elevation in risk of cancer while another analysis suggested that among those who were prescribed Regranex three or more times, there was an increase in the number of patients who died as a result of cancer.

BioMimetic has obtained a copy of a published abstract that provides data that is discussed in the FDA communication. The abstract titled "A Cohort Study of the Risk of Cancer in Regranex (Becaplermin) Users and Matched Comparators" can be found in the journal Pharmacoepidemiology and Drug Safety, 2007, Volume 16, Issue S2, pages S167-168. A full copy of the abstract can be purchased at the publisher's website, (http://www3.interscience.wiley.com/journal/114293165/issue). The study results reported in the abstract were obtained from data contained within the Ingenix Research Data Mart, a health insurance claims database. The reported results stated that there were 47 (2.9%) confirmed cancers among 1,622 becaplermin initiators and 86 (3.1%) confirmed cancers among 2,809 comparators (non-becaplermin treated). The abstract further indicated that there was no elevation in risk of cancer for subjects with one becaplermin dispensing compared to those with none or for subjects with three or more becaplermin dispensings compared to those with none.

In a separate mortality analysis based on 16 cancer deaths, the authors stated that there was an elevated risk for the four deaths among subjects with three or more becaplermin dispensings compared to those with none. The authors concluded, however, that the incidence of increased mortality "is based on a small number of cases and may reflect chance or residual confounding in the mortality models, which had too few deaths to address the confounders in the incidence." Moreover, a conclusion provided in the abstract stated that "this study suggests no relationship between becaplermin exposure and cancer incidence."

Based on these published study results, which BioMimetic has reviewed but did not take part in, BioMimetic does not believe that an increased risk for cancer or cancer deaths has been demonstrated for the chronic administration of becaplermin up to multiple months, much less for a single application of becaplermin as is done with the product candidates from BioMimetic Therapeutics.

BioMimetic obtained one FDA approved product, GEM 21S®, and has two product candidates in clinical development, GEM OS1 and GEM OS2. The product and product candidates contain the same drug product (becaplermin) as Regranex. For GEM 21S, over 50,000 units have been sold with no reported serious adverse events associated with the product. The use of GEM 21S for approved periodontal applications, and the ongoing clinical studies with GEM OS1 and GEM OS2 for orthopedic applications, use a single application of the product at the time of surgery, rather than multiple daily applications for up to 140 days, as is currently approved for Regranex.

As stated above, BioMimetic has not received any communications from the FDA related to today's web posting regarding Regranex. The Company will provide updates as new information becomes available.
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NewsBot · Jun 6, 2008

Update

Press Release from the FDA:
FDA Announces New Labeling Changes for Regranex
Product to carry boxed warning

The U.S. Food and Drug Administration today announced the addition of a boxed warning to the label of Regranex Gel 0.01% (becaplermin) to address the increased risk of cancer mortality in patients who use 3 or more tubes of the product. Regranex is a topical cream indicated for the treatment of leg and foot ulcers that are not healing in diabetic patients.

The WARNINGS section of the product has been updated to include a BOXED WARNING and a description of the epidemiologic data that is the basis for the revised label. These data come from a retrospective study that compared cancer incidence and cancer mortality among 1,622 patients exposed to Regranex to 2,809 otherwise similar patients who were not exposed. The results were consistent with no overall increase in cancer incidence among the patients exposed to Regranex. However, there was a five-fold increased risk of cancer mortality in the group exposed to three or more tubes of Regranex.

"In announcing this label change, FDA still cautions health care professionals to carefully weigh the risks and benefits of treating patients with Regranex," said Susan Walker, M.D., director of the Division of Dermatological and Dental Products. "Regranex is not recommended for patients with known malignancies."

In late March FDA issued an Ongoing Safety Review Communication on Regranex notifying the public that it was conducting a safety review. This follow-up communication is in keeping with FDA’s commitment to notify the public of any regulatory changes with this FDA approved product.

Regranex is a medicine that is a recombinant form of human platelet-derived growth factor which is applied directly to diabetic foot and leg ulcers that are not healing. The recombinant form of platelet growth factor has a biologic activity that is much like that produced naturally by the body. Growth factors cause cells to divide more rapidly. It is for this reason that the manufacturer continued to monitor studies begun before Regranex was approved in December 1997 for any evidence of adverse effects such as increased numbers of cancers. In a long term safety study completed in 2001, there were more deaths from cancer in people who used Regranex than in those who did not use it.

Following the report of the study completed in 2001, an additional study was performed using a health insurance database that covered the period from January, 1998 through June, 2003. This study used the database to identify two groups of patients with similar diagnoses, drug use, and use of health services, one of which used Regranex and one group that did not. The results of this study showed that deaths from cancer were higher for patients who were given three or more prescriptions for treatment with Regranex than those who were not treated with Regranex. No single type of cancer was identified, but rather deaths from all types of cancer, combined were observed.
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Link to FDA press release

Press Release from Johnson and Johnson:
ETHICON, INC. Announces Revised Label For REGRANEX® (becaplermin) Gel 0.01%

Somerville, NJ (June 6, 2008) -- ETHICON, INC. today announces revised labeling for REGRANEX Gel, a topical formulation of recombinant human platelet-derived growth factor indicated as an adjunct to the treatment of lower extremity diabetic neuropathic ulcers.

The WARNINGS section of the label has been updated to include a BOXED WARNING and a description of the epidemiologic data that is the basis for it. These data come from a retrospective study that compared cancer incidence and cancer mortality among 1,622 patients exposed to REGRANEX Gel to 2,809 matched comparators. The results were consistent with no overall increase in cancer incidence among patients exposed to REGRANEX Gel, however, there was a five- fold increased risk of cancer mortality in the group exposed to three or more tubes of REGRANEX Gel, based on four cases. The types of cancers varied and were remote from the treatment site.

The BOXED WARNING states "An increased rate of mortality secondary to malignancy was observed in patients treated with three or more tubes of REGRANEX Gel in a post-marketing retrospective cohort study. REGRANEX Gel should only be used when the benefits can be expected to outweigh the risks. REGRANEX Gel should be used with caution in patients with known malignancy."

The Company has worked closely with the FDA to ensure that the REGRANEX Gel label provides physicians and patients with the information they need to make the most appropriate and informed treatment decisions. ETHICON, INC. is committed to broadly disseminating this new prescribing information about the safety of REGRANEX Gel through a "Dear Healthcare Professional" letter and its field-based employees.

"We remain confident in the safety and efficacy of REGRANEX Gel when used according to its label," said James C. Hart, MD, Vice President, Global Medical Affairs, ETHICON. "The benefits of REGRANEX Gel have been established in well-controlled studies and confirmed in clinical practice."

REGRANEX Gel, manufactured by OMJ Pharmaceuticals, Inc. for its distributor Ortho-McNeil, is commercialized in the United States by Johnson & Johnson Wound Management, a division of ETHICON, INC.
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CNN are reporting:

Shares of New Brunswick, N.J.-based Johnson and Johnson fell $1.20 to $65.76
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NewsBot · Jul 16, 2008

Here some marketing spin, just received in the inbox from J & J:

Johnson & Johnson Wound Management is pleased to announce that REGRANEX Gel, ranked #1 in doctor satisfaction by Podiatrists and Surgeons in a survey of advanced wound therapies1, is once again available for you and your patients.

REGRANEX Gel, in conjunction with good wound care, has been proven to help heal diabetic foot ulcers more effectively than standard wound care. Diabetic Foot Ulcers can be deficient in growth factors2 and REGRANEX Gel is the first and only FDA-approved growth factor that activates cells to form new granulation tissue and blood vessels, closing DFUs fast.3 In a pivotal randomized controlled trial comparing REGRANEX Gel to placebo gel control, 50% of REGRANEX patients experienced complete wound closure at 20 weeks versus 35% in the control group and the average healing time was 12.3 weeks.4

Some wounds are difficult to heal. REGRANEX Gel can help this problem in many patients by delivering the growth factor directly to the ulcer in a simple-to-use gel.

Additionally, REGRANEX Gel has the evidence to prove it: in vitro, in vivo and in practice. From Randomized Controlled Trials to numerous patient case studies, the efficacy of REGRANEX Gel's is well supported and provides significant value to wound care clinicians and their patients.

"We want to do what's best for our patients, and we want to be sure that we're using cost effective therapy for treating our patients. So, it's very important that we have evidence or some science behind the therapies that we're using," said Dr. Terry Treadwell, MD, FACS, founder of the Institute for Advanced Wound Care and editor of Wounds peer-reviewed journal. "When we're looking for the best for our patient with evidence-based care, there are only a few options out there and REGRANEX is one of them."5

Diabetic Foot Ulcers are costly to treat and can become medical emergencies - they don't have to be. REGRANEX Gel has extensive insurance coverage making it accessible to your patients.
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NewsBot · Aug 9, 2008

Becaplermin gel in the treatment of diabetic neuropathic foot ulcers.
Papanas N, Maltezos E.
Clin Interv Aging. 2008;3(2):233-40.

Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery
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NewsBot · May 22, 2010

Benefit-risk assessment of becaplermin in the treatment of diabetic foot ulcers.
Papanas N, Maltezos E.
Drug Saf. 2010 Jun 1;33(6):455-61.

Becaplermin is a recombinant platelet-derived growth factor composed of two B chains that is approved for the treatment of neuropathic diabetic foot ulcers extending into or beyond the subcutaneous tissue in patients with adequate arterial perfusion. The aim of this review is to assess the benefits and risks associated with the use of this agent. Randomized controlled trials have provided evidence for the efficacy of becaplermin in increasing healing rates, and cost analyses have repeatedly shown a favourable cost-effectiveness ratio. However, clinical experience has not met these high expectations and becaplermin is not widely used. Moreover, this agent has not been compared with other additional treatment modalities, notably bioengineered skin substitutes and extracellular matrix proteins, and such comparisons are eagerly awaited. Of particular note, increased cancer risk has been reported in patients treated with more than three tubes of becaplermin; thus, this agent should be used only when the anticipated benefits outweigh the potential harm, and with extreme caution in patients with diagnosed malignancy. Finally, longer follow-up data are necessary to shed more light on the potential risk of malignancy in connection with becaplermin use.
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NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

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