Building A Business On Biodegradability

The original idea was simple: Take old construction industry techniques for replacing cast iron with plastic pipe and combine them with the biodegradability featured in surgeons' suture materials. The result would be a variety of medical body implants that are biodegradable.

That idea was the basis for Inion, a Finnish company started in 2000 to develop such implants. Its first product, launched in 2001, was a set of plates and screws to treat fractures to bones in the face, jaw, and skull caused either by trauma or the surgical correction of facial defects.

Beyond that, Inion has built up a set of products designed to treat breaks in wrists, ankles, hands, feet, and other places. It also has a series of products for sports medicine, a $250 million-plus global market that the company says is the fastest growing segment of the orthopedics industry. And late last year, it introduced a biodegradable spinal-fusion system for spinal care, a global market that, at $3.9 billion, is much larger than all of Inion's other target markets combined.

Moreover, the company is banking on a new range of polymers for implants that, spurred by the properties of a plasticizer they contain, actually hasten bone-healing.

Last year, the company rang up sales of $9.5 million, up 11% from 2004. Net losses were $12.3 million, compared with a loss of $10.2 million in 2004, reflecting in part a 79% increase in R&D expenses, to $5.4 million. The picture is becoming increasingly positive, however, insists Chief Executive Officer Auvo Kaikkonen, who predicts that Inion will probably turn a profit by the end of 2007.

One hurdle slowing sales growth has been the company's reliance on distributors, exemplified by a hiccup with a major distributor. As a result, some impatient shareholders have forced Inion into an extraordinary general meeting set for Aug. 15 that will reshape its board of directors.

This action is disruptive and "creates additional uncertainty around the direction of the company in the short term," observed Julie Simmonds, a stock analyst at London-based Piper Jaffray & Co., in a note to clients last month. "We are not convinced that the proposed new members add the med-tech/orthopedics sales expertise we believe is required."

What Simmonds and other analysts following the company are convinced of, though, is the opportunity in biodegradable implants. Key to their attractiveness is just — their degradability. Kaikkonen points out that in the U.K. and Finland, for example, every fifth orthopedic surgery is for removal of metal parts put in earlier to help bones heal.

Jorge de Seabra, an orthopedic surgeon who practices in Portugal, tells C&EN: "I think it will be a major breakthrough if we can use biodegradable implants the same way we now use metal devices, since surgery to extract the metal-which is almost always necessary-would be avoided."

De Seabra adds that there are some concerns about the strength of the current generation of biodegradable polymers: "We are limited to some minor surgery of the upper limb, or the use of some pins and screws in the ankle, although there is work going on to increase the strength of the materials." It is that kind of work that Inion is tackling, Kaikkonen says.

Inion's forerunner companies began clinical trials of biomedical implants in Helsinki in 1985. Research teams in the Netherlands, the U.S., and Japan were also pursuing biodegradable implants, but no one else had reached the point of clinical trials.

One forerunner, Bionx, was primarily interested in sports medicine applications for biodegradable materials. However, Kaikkonen recalls: "I was heading the R&D department of Bionx. I am an orthopedic surgeon, and I thought this was really a pretty neat thing to do across other surgical disciplines as well."

The company's location in Finland proved a big plus. There were a growing number of companies in Finland servicing telecommunications giant Nokia, including firms with the capability to injection-mold small, precise, thin-walled plastic parts. In late 1999, Kaikkonen and four Bionx R&D engineers resigned to launch Inion to exploit the medical implants market.

The company is now selling, through distributors, in more than 60 countries on four continents. About 50% of its sales are in the U.S., 30% in Europe, and 20% from the rest of the world.

The market is developing slowly, though, Simmonds noted in a research note. "Conversations with surgeons and distributors suggest that the reluctance to use the products is partly lack of familiarity with resorbables, partly cost, and partly the requirement for early sales support when using the products."

On the other hand, Kaikkonen counters, "we see tremendous awareness among patients-that sort of feedback is very positive. If patients are able to make a choice, more than 95% will pick the biodegradable over the permanent."

According to Kaikkonen, the first work in biodegradable implants relied on glycolic acid-based polymers. However, glycolic acid "caused too many tissue reactions"—in the range of about 12%—giving biodegradable plastic implants an initial bad reputation.

The industry then turned to lactic acid-based polymers, which had an adverse reaction rate that could be brought down to less than 1%. But the switch, in turn, compromised the biodegradability, he says. Glycolic acid-based polymers degrade within about one year, while lactic acid-based polymers take perhaps five years.

Today, on the principle that "no one size fits all," Inion's polymer palette includes l-polylactic acid, d,l-polylactic acid, trimethylene carbonate, and polyglycolic acid, to meet different demands. For example, in a system of plate and screws, the screws go through bone, which has higher vascularity than muscle. Consequently, screws degrade faster than the plates. Inion's solution is to blend polymers to tailor the degradation rate.

"Physical blending is well-characterized in technical polymers, but nobody had done this on medical polymers," Kaikkonen says. "We investigated everything on the [Food & Drug Administration] list, for example, and looked at the blending. We characterized more than 600 blends to come up with about 25 commercially available products." That exercise has given the company a library of materials, dubbed Optima, which it can tailor for strength, biodegradability, and design features.

Inion's latest range of polymers, OptimaPlus, features N-methyl pyrrolidone (NMP). This well-known plasticizer, Kaikkonen points out, is listed on FDA's master list of materials for use in polymers holding parenteral drug suspensions. Its incorporation into Inion's implants to improve handling characteristics, however, yielded a felicitous surprise.

During routine animal tests of the plasticized polymer at the University of Zurich, the company detected unexpected acceleration of bone healing, an effect it finally determined was being caused by the NMP. Now Inion is running clinical trials that indicate that the therapeutic use of NMP enhances bone healing by up to 50%.

Inion's central R&D center in Cambridge, England, is spearheading NMP development and exploring the potential of small molecules and other entities that might have bioactivity if administered in the right doses. "We have run through nearly 500 substances," Kaikkonen says.

In April, the company received a U.S. patent covering the combination of its biodegradable polymers with bone morphogenetic proteins and pyrrolidones such as NMP. The proteins are of particular interest because they prevent the abnormal formation of bone in nonbony tissue such as muscle. Such bone formation is observed in up to 50% of patients receiving spinal fusion surgery and in as many as 71% of patients receiving total hip replacements, the company says.

Further opportunities for Inion, Kaikkonen suggests, lie in developing a system to deliver these therapeutic molecules. Such a system could be an implant, a gel, or something entirely different. As Inion has done with its biodegradable materials, "We have to look at things in a different way," Kaikkonen says.