PERTH, Australia – Following stunning interim clinical results for its Celgro nerve regeneration treatment in quadriplegic patients, regenerative medicine company Orthocell Ltd. will focus all its efforts on gaining early FDA approval based on the early results.

Orthocell CEO Paul Anderson told BioWorld that interim results saw 96% of nerve repairs restored voluntary movement to previously paralyzed muscles, and that all quadriplegic patients increased movement and power of affected muscles following Celgro nerve regeneration treatment.

"This is an interim announcement of 12 patients in 12 months, and one of the exciting pieces of that is the movement from more simple nerve repairs to more complex nerve repairs for quadriplegic patients. It's been a stunning piece which has been so rewarding and such a fantastic set of outcomes for these patients who are continuing to improve," he said.

The original protocol didn't include quadriplegics. The treatment started with the simplest of these nerves, such as distal repairs in the lower arm, and then the team moved to the brachial plexus nerve in the shoulder, and then it went onto quadriplegic patients after seeing successful results.

"The old concept of curing quadriplegics through a magic stem cell bullet is really challenging and still a ways off," he said, noting that the focus has turned to giving function back to quadriplegics who have lung function but can't use their arms and legs. The surgery uses Celgro to join seven nerves together and to redirect some of those nerves in the arms.

Patients participating in the trial had previously suffered traumatic nerve injuries following motor vehicle, sporting and/or work-related incidents, resulting in impaired use of the affected limbs and, in more severe cases, quadriplegia (partial or total loss of use of all four limbs and torso).

Some patients experienced significant pain and were unable to perform basic daily tasks such as eating, bathing and dressing without assistance. In many cases, patients were unable to work and participate in recreational activities.

"Observing the positive progress of the initial patients gave me the confidence to use Celgro in more severe cases, such as quadriplegia," said Alex O'Beirne, orthopedic nerve specialist and clinical trial lead at St John of God Hospital in Murdoch, Western Australia.

Celgro is a collagen medical device scaffold that augments the surgical repair of damaged or degenerated tissue. The product acts as a scaffold that works with the tissues' own endogenous cells, or cells can be added to it.

"This bioactive chamber wraps around the nerve and not only protects it from the outside world but it enhances the repair mechanisms internally," Anderson said.

Trial results

A clinical follow-up of the first 12 patients 12 months after surgery found voluntary muscle movement was restored in 96% of nerve repairs, and 86% of patients who required prescription pain medication, including opioid-based drugs, were able to significantly reduce or stop their medication completely.

The procedures involved 25 nerve transfers augmented with Celgro. Participants had nerve injuries of varying severity, from peripheral nerve injury (three patients), to more complex injuries of the brachial plexus and spinal cord (nine patients in total), resulting in impaired use of the affected limbs and in the more severe cases, quadriplegia.

Roughly 66% of nerve repairs resulted in meaningful functional recovery of muscles controlled by the repaired nerve.

Almost half the nerve repairs (11 of 25) were performed in three quadriplegic patients. The results showed that 73% of nerve repairs resulted in meaningful functional recovery of affected muscles within 12 months. A quadriplegic patient with complete paralysis regained sufficient arm and hand function to perform tasks such as brushing teeth, drinking from a cup, and transferring into and out of his wheelchair.

The trial is expected to complete next year, and patients are continuing to improve out to the 24-month mark, the CEO said.

The interim data provides the company with the clinical data needed to get to Europe and Australia. Anderson said results "surpasses anything on the market," and he expects to get approval before the study is completed.

Competitive space

Although there are other collagen scaffolds on the market, they have come from medical device companies, not regenerative medicine, and the overwhelming focus has been on strength, Anderson said.

"This is one of the only collagen medical devices in the world that has been developed by regenerative medicine people that understand the cellular interactions.

"If you look at the other scaffold devices on the market, almost none of them are platform technologies, and that's because they don't meet the fundamental requirements for regenerative medicine. They're either too thick or too thin or too strong or not strong enough or simply don't integrate with the tissue well enough."

One major competitor in the U.S. is made from pigs' intestines and is very rigid, he said. Another product uses human skin from cadavers, which has "zero role to play in regenerative medicine," he said.

Celgro has marketing authorization in the EU for bone and tendon repair, and Orthocell has submitted an application to Australia's Therapeutic Goods Administration (TGA) for bone and tendon repair.

The company had been preparing a 510(k) to submit to FDA in the fourth quarter for the bone repair indication, but "because of these exciting results, we are now accelerating the regulatory approval processes in the U.S. for nerve regeneration, and we have started our communication with the FDA around what that package needs to look like."

He said he expects to submit the package early next year.

The CEO said the company will file European and Australian submissions simultaneously for the nerve regeneration indication. Nerve repair has the most potential in terms of outcomes for patients, he said.

"It's such a phenomenal set of outcomes and such an emotional story, that this is a company-making dynamic indication that we'll make a priority in our regulatory development process."

More than 20 million people in the U.S. suffer from peripheral nerve injury as a result of motor vehicle, sporting or work-related incidents, at an annual cost of about $150 billion. Celgro's addressable market in peripheral nerve repair is estimated to be worth more than $1.1 billion per year.

In June, Orthocell raised AU$10 million (16.5 million shares at AU40 cents per share) to accelerate commercialization of Celgro for dental bone, tendon and nerve repair into the U.S. market. The placement was not underwritten.

The company has enough runway for the next 24 months, which will take it to market and hopefully attract a partner in the U.S. or Europe, Anderson said.

Autologous stem cell therapies

Orthocell has commercialized two autologous cell therapies for treating damaged and degenerated tendons (Ortho-ATI) and damaged and degenerated cartilage (Ortho-ACI). Ortho-ATI is available in Australia and New Zealand for patients who have failed conservative treatment options such as corticosteroid injections and exercise programs and have ongoing symptoms.

The Australian company signed a partnership with Depuy Synthes Products for its Ortho-ATI stem cell technology for regenerating tendons and ligaments. That deal was facilitated by Johnson & Johnson Innovation in early 2017. (See BioWorld, Jan. 25, 2017.)

The Ortho-ATI intervention uses a patient's own tendon progenitor cells to stimulate the formation of collagen and other connective tissue elements. Those cells are taken from the tendon and cultured in a GMP facility in Western Australia where the volume of cells is expanded and then injected back into the patient via an ultrasound-guided method.

In clinical trials, the stem cell therapy has shown significant pain reduction and functional improvement in a range of different tendons. Clinical data at up to five years post intervention continue to demonstrate significant improvement in pain relief and function.

Orthocell's shares were trading on Australia's Securities Exchange (ASX:OCC) at AU48 cents (US32 cents). The company has a market cap of AU$68 million.

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