Regranex: Opening a Tube of It is like Opening Pandora’s Box

Armand Rossetti

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According to Sharon Bourke, et al., authors of a paper entitled, “A Photo-Cross-linked Poly(vinyl Alcohol) Hydrogel Growth Factor Release Vehicle for Wound Healing Applications” that appeared in the December issue of AAPS Pharmaceutical Sciences, Regranex gel, the only commercially available wound treatment using PDGF, shows only a moderate increase in the incidence of complete healing of diabetic ulcers (from 25% and 35% in placebo groups to 48% and 50% in treated groups, respectively.

Furthermore, Regranex is not the sole effective alternative to traditional care and treatment. In April 2004 a paper entitled, “Effectiveness of Oasis^® Wound Matrix Versus Regranex^® in Treating Diabetic Wounds” appeared in Wound Repair and Regeneration. Oasis wound Matrix is actually processed and end sterilized porcine small intestine, and patients can cut Oasis to size. Further information on Oasis is available at this website.

The author of the Oasis-Regranex comparison study presented interim data from 88 patients who participated in a multicenter, prospective, randomized clinical trial. Patients in the trial presented with chronic, full-thickness, diabetic ulcers and they received either weekly treatment with Oasis Wound Matrix or daily treatment with Regranex (becaplermin) gel. The patients then underwent evaluation after 12 weeks of treatment. The results showed that 53% of those treated with Oasis healed versus 35% of those who received Regranex treatment. As a result, Oasis treatment proved to be at least as effective as treatment using Regranex.

In fact, doctors and patients have many available alternatives to using Regranex. In addition to Oasis, Doctors may decide to use silver dressings like Aquacel Ag (ConvaTec) and Acticoat.

When applied, silver replaces sodium ions in the wound fluid and the silver ions act as antimicrobials to promote faster healing. The ConvaTec preparation is a silver impregnated dressing that uses hydrofiber, and which results in scaffold-type healing. Therefore, it is evident that unpredictable, blood vessel forming, platelet derived growth factor (PDGF) found in Regranex is not the only alternative to traditional treatment considting only of cleaning and debridement.

Likewise, doctors can choose to treat diabetic wound patients with Hyalofil (hyaluronan) a polysaccharide (sugar) glycosaminoglycan that is an important component of the gel like substance found in animal connective tissue. It is the same type of material that the Chinese were turning from being benign and beneficial to being dangerous by over-sulfating it to mimic heparin.

Once again, Regranex is platelet derived growth factor (PDGF), and as such it promotes angiogenesis, which means that it makes new blood vessels very rapidly. Scientists know that rapid blood vessel growth is good when it feeds the growth of normal cells, but that it is bad when the vessels feed cancerous cells. The problem is that PDGF does not discriminate between creating blood vessels for feeding good or bad cells.

We can see just the opposite effect on angiogenesis with Fosamax, where Fosamax (alendronate) causes less angiogenesis. The lack of normal angiogenesis may be a factor in slow healing of the jaws, and in the eventual promotion of osteonecrosis (death of bone cells in the jaw). Therefore it seems obvious that we do not want to influence the body in ways that we cannot control.

According to an article in the Annals of Internal Medicine (Volume 141, Number 2, 20 July 2004; “Current Clinical Issues”, pp. 165-68) the angiogenic switch is poorly understood:

“Abnormal angiogenesis appears to occur when cancer or other diseases control the normal processes of angiogenesis, a process triggered by the so-called angiogenic switch. The angiogenic switch, the precise molecular mechanisms of which are poorly understood, stimulates overproduction of proteins that promote angiogenesis by binding with receptors on endothelial cells.”

Besides, we have seen that Regranex marginally more effective in treating diabetes related wounds that available alternatives? BlueShield of Northeastern New York also understands that Regranex is an expensive alternative wound care therapy that is marginally more effective than alternatives:

“Notes:

• In a randomized, double-blind study of Regranex® gel (100mcg/g once daily for 16 weeks) in patients with Stage III or IV pressure ulcers, the incidence of complete ulcer closure was 15% (28/189) in the becaplermin group and 12% in the vehicle control group. The difference was not statistically significant.

• In two small, randomized, double-blinded studies of Regranex® gel (100mcg/g once daily for 16 weeks) in patients with venous stasis ulcers, the combined incidence of complete closure was 46% (30/65) in the becaplermin group and 39% (26/67) in the vehicle control group. The difference was not statistically significant.”

If the switch is poorly understood, then manufacturers have to be wary in cluding the switch in their products and placing the switch on the market.

Here is some surprising information that I have obtained.

Over the years, doctors from different subspecialties have come to realize that patients with Down syndrome (with three copies to chromosome 21 [trisomy 21]) have unsurpassed protection against certain diseases. For example, according to oncologists, cancer is almost unheard of among people with this syndrome. Cardiologists have seen that non-congenital heart problems rarely affect people with Down syndrome. Endocrinologists report that Down syndrome patients never present with diabetic retinopathy. Of course, until recently, nobody knew why this was the case.

However, in 2003, researchers discovered that the extra chromosome 21 in Down syndrome provides the body with an extra copy of “collagen XVIII,” which provides endostatin. And, Endostatin plays a key role in inhibiting angiogenesis (blood vessel growth). As mentioned, uncontrolled blood vessel growth is characteristic of cancer. However, excess blood vessel growth is also characteristic of heart disease and diabetic retinopathy- all the diseases that Down syndrome protects against.

In my first post on Regranex, I stated the following:

“Regranex is a recombinant form of human platelet-derived growth factor (PDGF), and it has a biologic activity that is similar to growth factor that the body produces naturally. Since growth factors cause cells to divide more rapidly, Regranex’ manufacturer, Ortho-McNeil (Ortho), continued to monitor studies begun before the FDA approved Regranex in December 1997, for evidence of adverse effects. Ortho Diagnostics was looking for evidence of increased numbers of cancers (Ortho-McNeil is a subsidiary of Johnson & Johnson (J&J)).”

Knowing what I know after a further, but brief investigation, I think that what the FDA is permitting Johnson & Johnson to do by marketing a product containing PDGF is the same as permitting borderline if not frank engagement in human experimentation. After all, if the angiogenic switch is poorly understood, the FDA should not be permitting Johnson & Johnson to be pulling that switch on unwary consumers.

Uncontrolled angiogenesis, dispensed as a salve from a tube, seems to be a very dangerous thing, and certainly a risk not worth taking.