Growth factors: The magic pill’ for promoting natural healing?
Procedure has good outcomes, but skeptics remain
A handful of biotechnology companies are searching for what could be the pot of gold at the end of the wound care rainbow. Namely, they are looking for a substance that unequivocally and reliably improves wound healing under a wide range of circumstances. Think of a magic salve that, once applied to a wound, immediately promotes healing.Obviously no such product exists, but some researchers are focusing on naturally occurring molecules known as growth factors, which are thought by many to play an important role in the intricate sequence of events that transpires during wound repair.
The notion that specific, identifiable, and isolatable chemicals within the body might be harnessed to heal wounds is a tempting notion for biotechnologists seeking a magic salve for chronic wounds. But turning theory into practice has proved a vastly complex and elusive exercise.
Only one growth factor, Procuren (actually a combination of several individual growth factors), is in widespread use in the United States. Procuren is a platelet-derived growth factor assayed from a small sample (110-150 cc) of the patient’s own blood. Once the platelets are separated from the blood sample and exposed to thrombin — an enzyme involved in the conversion of fibrin to fibrinogen, which is crucial for blood clotting — they release a variety of growth factors.
The final compound is a topical ointment containing not one but several growth factors that are thought to play important roles in the early phases of wound healing. Because Procuren is autologous, it is not considered a pharmaceutical and thus does not need marketing approval from the U.S. Food and Drug Administration (FDA).
In contrast to autologous growth factors, recombinant growth factors are lab-synthesized copies of the body’s naturally occurring substances. (See story on growth factor science, p. 88.) A number of companies are researching these molecules for use in wound healing, but the number of patients receiving treatment is relatively small, and clinical data are scarce. Considered pharmaceuticals, recombinant growth factors are regulated by the FDA. None has received marketing approval.
Procuren is manufactured by Curative Health Services in East Setauket, NY. Curative also operates about 150 wound care franchises around the United States, often subcontracting its program to individual hospitals; Procuren is often part of the company’s standardized wound care protocol.
Too good to be true?
Procuren was used to treat about 38,000 wound patients between 1988 and 1996, says Mark Doyne, MD, Curative’s vice president of medical affairs. A number of clinical studies, both prospective and retrospective, have been conducted on the agent. Curative touts a cure rate of 82% among patients who complete the Procuren program. The company also claims that the program reduces the cost of patient care.
A complete Procuren regimen lasts about 16 weeks — fewer if healing occurs more rapidly. Individual hospitals set the cost, which reportedly ranges from $60 to $80 per day, Doyne says.
But Curative’s prominence and its claims of Procuren’s effectiveness also have made it a target of harsh criticism. The most common charge is that Curative has not shown conclusively that Procuren alone, and not Curative’s extensive wound care protocol, is directly related to measurable wound healing responses.
Curative’s approach to wound care has been described as aggressive, and the company prides itself on its multidisciplinary, thorough treatment protocols. All patients consult with physicians and nurses. If necessary, they receive X-rays, full blood work-ups, and vascular testing. Wounds often are debrided surgically.
Damning with real praise
Ironically, some of the same people who question Procuren’s efficacy laud Curative’s program. "It’s well-contained. All wound care programs should be as good as that," comments one wound care clinician who is skeptical of Procuren.
Another clinician familiar with Curative’s program, who also requested anonymity, added: "I’m not really sure if it’s the autologous growth factors that are having the positive effects on healing, because Curative is so aggressive with wound debridement. If you take a wound that is full of dead tissue and clean it up to good healthy bleeding tissue and then apply growth factors, it’s going to be very difficult to tell whether all of the effect is from growth factors or the combination of everything else Curative is doing."
As proof of its success, Doyne points to a study conducted by Arthur D. Little Inc. (and partially funded by Curative). That research compared the cost-effectiveness of comprehensive wound management with and without Procuren. The investigators concluded that the program including Procuren was about 40% less expensive per patient healed compared with the non-Procuren regimen. A series of other clinical studies, both prospective and retrospective, also seems to bathe Procuren in a favorable light.
Still, not everyone is convinced about what is causing the good outcomes. "In the scientific community, many clinicians feel that Curative has not made an impressive demonstration of the efficacy of its growth factor formula," says Jeffrey M. Davidson, PhD, professor of pathology at the Vanderbilt University School of Medicine and a research scientist at the Department of Veterans Affairs Medical Center in Nashville, TN.
"That’s probably because of the overall treatment effect. But if you look at the total technology, it seems to be very effective in wound treatment, and Procuren is part of the package," Davidson explains.
How much?
The cost of the treatment also raises concerns for some. Sources who have worked with the Curative program tell Wound Care that the actual cost can be far higher than Curative’s estimate, even reaching into many thousands of dollars early in the treatment period. Curative reiterates that pricing is determined by individual facilities.
In addition, if results are unsatisfactory after a properly followed, standard 16-week Procuren clinical pathway, all future Procuren for that patient will be supplied at no charge, says Victoria Travis, MSHA, program director of Curative’s Denver Wound Care Center.
Critics point out that despite Curative’s public praise of Procuren, only about a quarter of Curative patients receive it. "If it were really a panacea, [Curative] would use it on everybody, and everybody would be healing," says one clinician. "They tend to be very careful about who they try growth factors on."
Doyne responds by saying that the patient selection process is indeed very careful. "Procuren jump-starts or stimulates the body’s natural healing process," he says. "It’s applied in situations where there is an increased risk to healing, such as in patients where revascularization is not possible or has failed, in immunocompromised patients, or in patients where healing has been resistant for other reasons. It’s not a magic bullet. If there’s not adequate blood supply to the wound, for instance, it won’t work. Procuren should be used in the context of a well-organized, comprehensive wound care program."
Medicare steps back
Finally, Curative drew unwanted attention when Medicare, which had reimbursed for Procuren, dropped that coverage after deciding that there wasn’t enough proof of its effectiveness. The proportion of Curative patients who received Procuren quickly dropped from about 80% to its current 25%.
Curative admits the sharp decline. "Yes, that’s true," Travis says. "With all medications, all healing tools, sometimes there’s an initial overuse. Then the medical community sees what the results are and is able to adjust. I think that’s exactly what happened with Medicare and Procuren."
Curative says that about 300 commercial health insurance payers cover Procuren and that the number is growing. But the largest percentage of Procuren patients are on Medicare and fixed incomes. "We will find a way to get them Procuren, which may include a sliding-fee scale," Travis says.
Nature’s cocktail’
Despite the barrage of criticism, others in the growth factor hunt recognize the potential of Procuren.
"There’s good rationale to believe that using a combination of several growth factors is a good way to stimulate healing," explains John McPherson, PhD, senior vice president of research and development at the Genzyme company in Framingham, MA, which is researching recombinant platelet-derived growth factor.
"It’s sort of nature’s own cocktail of growth factors normally involved in initiating or stimulating wound healing responses," McPherson says. (For more information on Genzyme’s efforts, see story, p. 86.)
Reference
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