Stem cell therapies needing more regulatory acceptance

As historic events go the approval of Osiris Pharmaceuticals' stem cell treatment Prochymal in Canada, making it the first regulatory approval for the technology outside of China, received a relatively muted response both in the wider pharma community and the financial one.

The lack of fanfare might have had something to do with the fact that the green light was given in the small market of Canada and in the super niche indication of paediatric graft versus host disease. But Prochymal’s reception could speak more about the ongoing difficulties many see to getting wider regulatory approval and acceptance for cell-based therapies and their need to prove not only their efficacy, but safety.

The fact that Prochymal is the first western approved product since stem-cell-based therapies first made their debut in the form of bone marrow transplants in 1968 underlines the struggle of making it to the market (Osiris' battles will continue despite landmark approval for Prochymal, May 21, 2012).

Neither fish nor fowl

The chief hurdle that many stem-cell-based therapies face when put in front of the regulators is that the system is geared up to assess distinct types of products including pharmaceuticals, biotechnology or devices, argues Dean Tozer, senior vice president corporate development at Advanced BioHealing. “If you look at regenerative products many incorporate elements of if not two, maybe all three of those disciplines.”

A lack of an appropriate framework is also what Dr Gopalan Narayanan, expert medical assessor of the biologicals unit licensing division of the Medicines and Healthcare Products Regulatory Agency, also believes is hindering stem-cell-based therapies trying to tread the regulatory path to approval.

Speaking at the World Stem Cells Regenerative Medicine Congress Dr Gopalan, argued even the traditional phase I, II and III trials are often not applicable to stem cell treatment. “These no longer make sense, these drugs are often developed in very niche orphan indications, so doing phase I safety trials, or even phase II dosing trials does not apply.”

New models needed

As well as being very disease specific, cell therapies can be patient specific, again flying counter to traditional models of drug discovery. In addition, as many stem cell therapies are expected to renew themselves and will remain in the body for long periods of time, like Prochymal, long post approval follow ups maybe required to continue to monitor their safety and efficacy.

Mr Tozer says that what is needed to help stem cell and other regenerative products through the regulatory system is closer collaboration with the regulators to determine “what is the appropriate level of assessment and type of assessment for these cell-based therapies”.

There have been moves by the industry to facilitate this and Advanced BioHealing, which is now part of Shire following the UK group’s 2011 $750m buyout of the private company hours before it priced its IPO, is one of the founders of the Alliance for Regenerative Medicine in the US, which represents industry, academia and patient groups interested in the field of regenerative medicine.

Mr Tozer says there is a real interest on the part of regulators to talk about the technology because of its evolution and involvement with multi-disciplinary teams. “I’ve been in this space for the last six years and in the last nine months both regulatory and reimbursement parts of the healthcare system are starting to step back and say ‘wow this stuff is real, how are we going to deal with it?’".

Success breeds success

But while the amount of talk around regenerative medicine products might be increasing, the action both in terms of getting products to late stage trials and approvals remains low.

Advanced BioHealing can claim one of the few regenerative medicines on the market, its treatment for diabetic foot ulcers, Dermagraft, but it is in a very small and elite club.

Shire may have spotted the potential in regenerative medicine with its buyout of Advanced BioHealing, but the majority of large pharma has continued to sit on the sidelines waiting for a big breakthrough in the technology.

The UK pharma group’s decision to pick up Advanced BioHealing may also have been down to the fact that rather than being a risky experimental drug Dermagraft was approved and is generating revenues. 

Finding the money

For the smaller companies with less developed products the difficulties they are having getting to market is because of lack of investment, something that is compounded by the lack of success in the field and later stage products.

“A shift has to happen in the way that people think about funding these types of developments,” says Mr Tozer. “Traditionally what was done was a biotech model, you funded it to phase II and then you went out and shopped it around and some big pharma picked it up and put in the resources to do a full blown phase III programme, and if the product worked it would be approved. One of the challenges we have as an industry is that there have not been those big phase III trials and so now the challenge is getting the capital in to support those trials.”

What might now help bridge that funding gap is that Shire has decided to make Advanced BioHealing the cornerstone of its regenerative medicines business and has provided the division with money and resources to find and develop new products.

Shire will not be able, or willing, to scoop up all the regenerative medicine products in development, but for the ones that they do choose - last month they said they would be paying up to $200m to secure Pervasis Therapeutics - they will have the backing and expertise of a big pharma group that should help them navigate the regulatory process.

As well as potentially improving the success rates in the field, their involvement could also drive interest from other pharma groups.