Streamlining Stem Cell Therapy Development for Impatient Patients

During this third week of the Month of CIRM, we are focusing on CIRM’s Infrastructure programs which are all focused on helping to accelerate stem cell treatments to patients with unmet medical needs.

Time is money. It’s a cliché but still very true, especially in running a business. The longer it takes to get things done, the more costs you’ll most likely face. But in the business of developing new medical therapies, time is also people’s lives.

Currently, it takes about eight years to move a promising stem cell treatment from the lab into clinical trials. For patients with fatal, incurable diseases, that is eight years too long. And even when promising therapies reach clinical trials, only about 1 out of 10 get approved, according to a comprehensive 2014 study in Nature Biotechnology. These sobering stats slow the process of getting treatments to patients with unmet medical needs.

While a lack of therapy effectiveness or safety play into the low success rate, other factors can have a significant impact on the delay or suspension of a trial. An article, “Why Do Clinical Trials Fail?” in Clinical Trials Arena from a couple years back outlined a few. Here’s a snippet from that article:

  • “Poor study design: Selecting the wrong patients, the wrong dosing and the wrong endpoint, as well as bad data and bad site management cause severe problems.”
  • “Complex protocol: Simple is better. A complex protocol, which refers to trying to answer too many questions in one single trial, can produce faulty data and contradictory results.”
  • “Poor management: A project manager who does not have enough experience in costing and conducting clinical trials will lead to weak planning, with no clear and real timelines, and to ultimate failure.”

CIRM recognized that these clinical trial planning and execution setbacks can stem from the fact that, although lab researchers are experts at transforming an idea into a candidate therapy, they may not be masters in navigating the complex regulatory requirements of the Food and Drug Administration (FDA). Many simply don’t have the experience to get those therapies off the ground by themselves.

Lab researchers are experts at transforming an idea into a candidate therapy but most are inexperienced at navigating the complex regulatory requirements of the Food and Drug Administration (FDA).

So, to help make this piece of the therapy development process more efficient and faster, the CIRM governing Board last year approved the launch of the Translating Center and Accelerating Center: two novel infrastructure programs which CIRM grantees can tap into as they carry their promising candidate therapies from lab experiments in cells to preclinical studies in animals to clinical trials in people. Both centers were awarded to QuintilesIMS which collectively dubbed them The Stem Cell Center.

The Stem Cell Center acts as a one-stop-shop, stem cell therapy development support system for current and prospective CIRM grantees, giving them advanced priority for QuintilesIMS services. So how does it work? When a scientist’s initial idea for a cell therapy gains traction and, through a lot of effort in the lab, matures into a bona fide therapy candidate to treat a particular disease, the next big step is to prepare the therapy for testing in people. But that’s easier said than done. To ensure safety, the Food and Drug Administration requires a rigorous set of tests and documentation that make up an Investigational New Drug (IND) application, which must be submitted before any testing in people take can place in the U.S.

That’s where the Translation Center comes into the picture. It carries out the necessary research activities to show, as much as is possible in animals, that the therapy is safe. The Translating Center also helps at this stage with manufacturing the cell therapy product so that it’s of a consistent quality for both the preclinical and future clinical trial studies. If all goes as planned, the grantee will have the necessary pieces to file an IND. At this stage, the Translating Center coordinates with the Accelerating Center which focuses on supporting the many facets of a clinical study including the IND filing, clinical trial design, monitoring of patient safety, and project management.

Because the work of Translating and Accelerating Centers is focused on these regulatory activities day in and day out, they have the know-how to pave a clearer path, with fewer pitfalls, for the grantee to navigate the complex maze we call cell therapy development. It’s not just helpful for the researchers seeking approval from the FDA, but it helps the FDA too. Because cell therapies are still so new, creating a standardized, uniform approach to stem cell-based clinical trial projects will help the FDA streamline their evaluation of the projects.

Ultimately, and most importantly, all of those gears running smoothly in sync will help leave a lasting legacy for California and the world: an acceleration in the development of stem cell treatment for patients with unmet medical needs.

CIRM Alpha Clinics Network charts a new course for delivering stem cell treatments

Sometimes it feels like finding a cure is the easy part; getting it past all the hurdles it must overcome to be able to reach patients is just as big a challenge. Fortunately, a lot of rather brilliant minds are hard at work to find the most effective ways of doing just that.

Last week, at the grandly titled Second Annual Symposium of the CIRM Alpha Stem Cell Clinics Network, some of those minds gathered to talk about the issues around bringing stem cell therapies to the people who need them, the patients.

The goal of the Alpha Clinics Network is to accelerate the development and delivery of stem cell treatments to patients. In doing that one of the big issues that has to be addressed is cost; how much do you charge for a treatment that can change someone’s life, even save their life? For example, medications that can cure Hepatitis C cost more than $80,000. So how much would a treatment cost that can cure a disease like Severe Combined Immunodeficiency (SCID)? CIRM-funded researchers have come up with a cure for SCID, but this is a rare disease that affects between 40 – 100 newborns every year, so the huge cost of developing this would fall on a small number of patients.

The same approach that is curing SCID could also lead to a cure for sickle cell disease, something that affects around 100,000 people in the US, most of them African Americans. Because we are adding more people to the pool that can be treated by a therapy does that mean the cost of the treatment should go down, or will it stay the same to increase profits?

Jennifer Malin, United Healthcare

Jennifer Malin from United Healthcare did a terrific job of walking us through the questions that have to be answered when trying to decide how much to charge for a drug. She also explored the thorny issue of who should pay; patients, insurance companies, the state? As she pointed out, it’s no use having a cure if it’s priced so high that no one can afford it.

Joseph Alvarnas, the Director of Value-based Analytics at City of Hope – where the conference was held – said that in every decision we make about stem cell therapies we “must be mindful of economic reality and inequality” to ensure that these treatments are available to all, and not just the rich.

“Remember, the decisions we make now will influence not just the lives of those with us today but also the lives of all those to come.”

Of course long before you even have to face the question of who will pay for it, you must have a treatment to pay for. Getting a therapy through the regulatory process is challenging at the best of times. Add to that the fact that many researchers have little experience navigating those tricky waters and you can understand why it takes more than eight years on average for a cell therapy to go from a good idea to a clinical trial (in contrast it takes just 3.2 years for a more traditional medication to get into a clinical trial).

Sunil Kadim, QuintilesIMS

Sunil Kadam from QuintilesIMS talked about the skills and expertise needed to navigate the regulatory pathway. QuintilesIMS partners with CIRM to run the Stem Cell Center, which helps researchers apply for and then run a clinical trial, providing the guidance that is essential to keeping even the most promising research on track.

But, as always, at the heart of every conference, are the patients and patient advocates. They provided the inspiration and a powerful reminder of why we all do what we do; to help find treatments and cures for patients in need.

The Alpha Clinic Network is only a few years old but is already running 35 different clinical trials involving hundreds of patients. The goal of the conference was to discuss lessons learned and share best practices so that number of trials and patients can continue to increase.

The CIRM Board is also doing its part to pick up the pace, approving funding for up to two more Alpha Clinic sites.  The deadline to apply to be one of our new Alpha Clinics sites is May 15th, and you can learn more about how to apply on our funding page.

Since joining CIRM I have been to many conferences but this was, in my opinion, the best one I have ever intended. It brought together people from every part of the field to give the most complete vision for where we are, and where we are headed. The talks were engaging, and inspiring.

Kristin Macdonald was left legally blind by retinitis pigmentosa, a rare vision-destroying disease. A few years ago she became the first person to be treated with a CIRM-funded therapy aimed to restoring some vision. She says it is helping, that for years she lived in a world of darkness and, while she still can’t see clearly, now she can see light. She says coming out of the darkness and into the light has changed her world.

Kristin Macdonald

In the years to come the Alpha Clinics Network hopes to be able to do the same, and much more, for many more people in need.

To read more about the Alpha Clinics Meeting, check out our Twitter Moments.

License to heal: UC Davis deal looks to advance stem cell treatment for bone loss and arthritis

Nancy Lane

Wei Yao and Nancy Lane of UC Davis: Photo courtesy UC Davis

There are many challenges in taking even the most promising stem cell treatment and turning it into a commercial product approved by the Food and Drug Administration (FDA). One of the biggest is expertise. The scientists who develop the therapy may be brilliant in the lab but have little experience or expertise in successfully getting their work through a clinical trial and ultimately to market.

That’s why a team at U.C. Davis has just signed a deal with a startup company to help them move a promising stem cell treatment for arthritis, osteoporosis and fractures out of the lab and into people.

The licensing agreement combines the business acumen of Regenerative Arthritis and Bone Medicine (RABOME) with the scientific chops of the UC Davis team, led by Nancy Lane and Wei Yao.

They plan to test a hybrid molecule called RAB-001 which has shown promise in helping direct mesenchymal stem cells (MSCs) – these are cells typically found in the bone marrow and fat tissue – to help stimulate bone growth and increase existing bone mass and strength. This can help heal people suffering from conditions like osteoporosis or hard to heal fractures. RAB-001 has also shown promise in reducing inflammation and so could prove helpful in treating people with inflammatory arthritis.

Overcoming problems

In a news article on the UC Davis website, Wei Yao, said RAB-001 seems to solve a problem that has long puzzled researchers:

“There are many stem cells, even in elderly people, but they do not readily migrate to bone.  Finding a molecule that attaches to stem cells and guides them to the targets we need provides a real breakthrough.”

The UC Davis team already has approval to begin a Phase 1 clinical trial to test this approach on people with osteonecrosis, a disease caused by reduced blood flow to bones. CIRM is funding this work.

The RABOME team also hopes to test RAB-001 in clinical trials for healing broken bones, osteoporosis and inflammatory arthritis.

CIRM solution

To help other researchers overcome these same regulatory hurdles in developing stem cell therapies CIRM created the Stem Cell Center with QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider that has deep experience and therapeutic expertise. The Stem Cell Center will help researchers overcome the challenges of manufacturing and testing treatments to meet FDA standards, and then running a clinical trial to test that therapy in people.

Creating a “Pitching Machine” to speed up our delivery of stem cell treatments to patients

hitting-machine

When baseball players are trying to improve their hitting they’ll use a pitching machine to help them fine tune their stroke. Having a device that delivers a ball at a consistent speed can help a batter be more consistent and effective in their swing, and hopefully get more hits.

That’s what we are hoping our new Translating and Accelerating Centers will do. We call these our “Pitching Machine”, because we hope they’ll help researchers be better prepared when they apply to the Food and Drug Administration (FDA) for approval to start a clinical trial, and be more efficient and effective in the way they set up and run that clinical trial once they get approval.

The CIRM Board approved the Accelerating Center earlier this summer. The $15 million award went to QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider.

The Accelerating Center will provide key core services for researchers who have been given approval to run a clinical trial, including:

  • Regulatory support and management services
  • Clinical trial operations and management services
  • Data management, biostatistical and analytical services

The reason why these kinds of service are needed is simple, as Randy Mills, our President and CEO explained at the time:

“Many scientists are brilliant researchers but have little experience or expertise in navigating the regulatory process; this Accelerating Center means they don’t have to develop those skills; we provide them for them.”

The Translating Center is the second part of the “Pitching Machine”. That is due to go to our Board for a vote tomorrow. This is an innovative new center that will support the stem cell research, manufacturing, preclinical safety testing, and other activities needed to successfully apply to the FDA for approval to start a clinical trial.

The Translating Center will:

  • Provide consultation and guidance to researchers about the translational process for their stem cell product.
  • Initiate, plan, track, and coordinate activities necessary for preclinical Investigational New Drug (IND)-enabling development projects.
  • Conduct preclinical research activities, including pivotal pharmacology and toxicology studies.
  • Manufacture stem cell and gene modified stem cell products under the highest quality standards for use in preclinical and clinical studies.

The two centers will work together, helping researchers create a comprehensive development plan for every aspect of their project.

For the researchers this is important in giving them the support they need. For the FDA it could also be useful in ensuring that the applications they get from CIRM-funded projects are consistent, high quality and meet all their requirements.

We want to do everything we can to ensure that when a CIRM-funded therapy is ready to start a clinical trial that its application is more likely to be a hit with the FDA, and not to strike out.

Just as batting practice is crucial to improving performance in baseball, we are hoping our “Pitching Machine” will raise our game to the next level, and enable us to deliver some game-changing treatments to patients with unmet medical needs.