Although stem cell research has sparked controversy for years, Osiris Therapeutics has quietly been flying under the radar for a decade with a revolutionary secret. The company is in the final stages of developing Prochymal, widely expected to be the first-ever FDA approved stem cell drug.  With a pre Biologics License Application (pre-BLA) meeting already under their belt, and an FDA OK for Prochymal use in adult Graft vs. Host Disease (GvHD) patients, Osiris is steadily marching toward the finish line.

According to President and CEO Randall Mills, with about 300 patents issued worldwide and a contract with the US Department of Defense for Acute Radiation Syndrome treatments, “there’s nobody else in the ballpark of where we are right now.” And that’s not to mention Osiris’ three other indications currently in pivotal trials.

Before joining Osiris, Mills was an executive officer of Regeneration Technologies, a company that deals with tissue transplantation. When he joined Osiris in 2004, Mills couldn’t believe the potential of stem cell technology. Four years later, he’s just as enthusiastic about the progress Osiris is making. Pharm Exec sat down with Mills to discuss what’s next for the stem cell industry, and how Osiris demonstrated that it’s possible to turn interesting science into a lucrative business.

What is the promise of stem cells?
The introduction of stem cell therapy will be as profound to the practice of medicine as the introduction of antibiotic therapy in 1929 and 1930, when sulfa and penicillin drugs were discovered. We’re on that level of change in medicine. The introduction of stem cells is going to change the way physicians think about and approach the practice of medicine.

How do you get stem cells, and have you had to work with any third parties to regulate your research?
From the research side, the stem cell source we use is completely unregulated. In fact, you’re able to do whatever research you want on any kind of stem cell. The only restriction is that you can’t get federal funding for research involving embryonic stem cells, unless it comes from specific stem cell lines. 

We get our stem cells from bone marrow of healthy young adults between the ages of 18 and 30. Bone marrow contains a number of different cells, but we use only the mesenchymal stem cell, or the MSC. Once we collect them, we’re able to expand the cells to produce 10,000 doses of our drug. The process by which we grow stem cells is a fairly standard GMP compliant biotechnology and manufacturing process.

We don’t get involved in the harvesting of the bone marrow. Many companies collect bone marrow, so we can literally buy it off the shelf. It’s inexpensive, noncontroversial, and we can get as much as we need. Because we mass produce the product at low costs, we’re able to transform this technology from interesting science into a business.

Your new drug, Prochymal, can be used to combat heart attacks, diabetes and nuclear terrorism. How do you develop a platform drug that can be used for such varying problems?
MSCs do three things: They downregulate inflammation, they work to regenerate the damaged connective tissue, and they prevent scarring or fibrosis. That’s the Holy Trinity of the mesenchymal stem cell. It’s the natural progression or sequence of how we respond to injury. When we’re young, that process works well. Children heal in miraculous ways.  Conversely, an elderly person will die of something like a fractured hip. This is because children have 1,000-fold more MSC in their body than adults do. What happens is an adult ends up with a very exaggerated inflammatory response, a weak regenerative response, and a lot of scarring. We can reverse that trend by administering MSC.

Because MSCs naturally have a broad range of things they can respond to, our job is to package them as something that will satisfy the FDA. We need scientifically sound clinical trials that show a significant benefit in a particular patient population.

Is patenting intellectual property the same in this area as in other areas?
It’s a little bit different because it’s a brand new field. Being in a new industry like ours means there are things other than specific formulations of drugs you can patent.

We have what’s called a “composition of matter” patent around the mesenchymal stem cell itself, but we also have patents on how you manufacture cells for intravenous infusion, how you formulate a product like this, and how you test a product for lot release.

What’s happening in stem cell work now as compared to 2004? 
We’re further along in stem cell technology and stem cell therapies than people think we are. Osiris has led the way by demonstrating that stem cells are real and they’re real right now. This is a here and now thing.

The FDA recently gave us expanded access approval. We can now treat children 17 years of age and younger with our product.  In 2004, it was unthinkable that a stem cell product could be routinely used in the treatment of any patient population, let alone children.

When I came to Osiris in 2004, Osiris was what I called Osiris University. It was highly academic, brilliant people doing great science, but there was no commercial focus. That’s changed nicely over the last four years because companies have been rewarded in the share price of their overall value or market cap. The really good news is that the change ultimately helped patients. To date, we’ve treated more than 20,000 patients with Osteocel.

Who would you consider your closest competitor to date?
There’s nobody else in the ballpark of where we are right now. It’s a pretty long walk. But Geron is the most advanced in credible embryonic stem cell work, and Cytori is making a device that can extract cells from fat. The good news is that these companies are taking a business approach towards cell therapy and the commercialization of stem cells. And that is a change since 2004 that’s helping everybody.

Because this is such a new area, does the infrastructure need to be developed, perhaps even outside your company?
Not as much as you would think. If you saw a patient getting Prochymal, you wouldn’t be able to tell it apart from a patient getting any other drug. It just drips in through a standard IV line. And it’s not logistically hard to move around. We are already treating patients with Prochymal all around the world, so the commercial infrastructure really isn’t that big of an issue.

But I don’t think the FDA had as much work to do from a regulatory standpoint as the companies preparing to be regulated. The FDA actually has reasonable regulations in place for stem cell therapy, but the industry had to come to grips with the requirements. FDA expects us to demonstrate that our products are safe and effective. That’s the standard we are held to. It’s the same standard that every drug is held to.

FDA has borne the brunt of the tremendous disparity between interesting preclinical scientific discoveries and what it actually means to translate a product into something that’s usable everyday.

When do you expect to hear from FDA?
We have fast-track status on all three of our pivotal programs. We haven’t submitted our Biologic License Application (BLA) yet, so we’re going to at least let them get the BLA before we start demanding approval.

When do you plan to submit your BLA?
We’ll start submitting the BLA at the end of this year, and we’ll probably compete it around summertime. Because we have fast-track status, we can submit it on a rolling basis.

What do you see as your biggest challenges in the next year?
Other than bringing the first stem cell product in the history of the world to the FDA? The biggest challenges we have are the biggest challenges any drug company has: We have to stay focused; we have to enroll our clinical trials, finish them up, collect the data, and get it to FDA. We have a lot of things to make sure we do well—executing them is our biggest challenge.