Anticipated short-term cell therapy industry clinical milestones

Tweet 

What follows is an interesting but not exhaustive list of cell therapy industry clinical milestones we anticipate in the next 3-9 months as selected from the list of cell therapy products we are tracking in late-stage or post-commercial development.  

There are other commercial milestones we are monitoring as well as other clinical milestones we expect to see related to cell therapy products in earlier stages of the development pipeline that are not included below.

CellCoTec (www.cellcotec.com)

• Having completed a trial in Europe of their device to enable POC production of an autologous chondrocyte cellular product in/with a biodegradable, load-bearing scaffold for the treatment of articular cartilage defects, they have now submitted their CE market application.  The CE mark application is under review and they anticipate a response in October.  

• This device and the potential emergence of Sanofi's MACI in the European market next year may have an impact on Tigenix (EBR:TIG) most directly.

ERYtech Parma (www.erytech.com)

• Their 'pivotal' phase 2/3 trial in Europe of lead product, GRASPA, for the treatment of Acute Lymphoblastic Leukemia (ALL) is scheduled for completion 2H 2013. 

GamidaCell (www.gamidacell.com)

• Their 'pivotal' phase 2/3 trial in the US, Israel, and Europe of lead product, StemEx, for the treatment of leukemia and lymphoma, in joint development with Teva, completed enrollment in February and is scheduled for completion 2H 2012.  They have not been shy about the fact they expect to be in the market in 2013.

Innovacell (www.innovacell.com)

• They raised over 8m Euro in April for a phase 3 trial in Europe for their lead product, ICES13, for the treatment of stress-urinary incontinence which was scheduled for a preliminary clinical data readout in Q4 2012 and be ready for market authorization in 2013. Since announcing the capital raise the company has been stone silent and no clinical trial registry has been filed.  Status unknown.

Miltenyi Biotec (www.miltenyibiotec.com)

• Their phase 3 trial in Germany of CD133+ cells as an adjunct to CABG surgery for myocardial ischemia or coronary artery disease is scheduled for completion in January.

NovaRx (www.novarx.com)

• Their phase 3 trial in US, Europe, and India of their lead product, Lucanix, for the treatment of advanced Non-small Cell Lung Cancer (NSCLC) following front-line chemotherapy is scheduled in clnicaltrials.gov for completion in October but we have learned they expect their next 'interim analysis' in February.

NuVasive (www.nuvasive.com)

• They have a series of trials scheduled to complete 2H 2012 intended to provide additional clinical data to support its marketing of Osteocel Plus for the treatment of a growing number of orthopedic applications.

Sanofi's Genzyme (www.genzyme.com)

• Having completed their phase 3 trial in Europe of MACI for knee repair (symptomatic articular cartilage defects of the femoral condyle including the trochlea), they expect to file their market authorization application (MAA) in 1H 2013.

Hope that's helpful and gives you a sense some of the late-stage things to watch for in the coming weeks and months.  

--Lee

Cell Therapy HiLites 2008-12-05

While the cell therapy sector certainly has more than its fair share of companies spreading their peanut butter thinly to survive their burn rate until their next financing closes, another week of funding news and milestones means its not all bad news out there for the cell therapy industry.

Pluristem Therapeutics Inc. (NasdaqCM:PSTI) announced $750,000 of new investment funds - well actually $600,000 from a restricted share purchase and an additional $150,00 from management and BOD members by way of reduced compensation. But the investor has the option, within 10 business days following the initiation of the Company's first human clinical trial, to put in another $600,000.

Osiris completed enrollment in its first Phase III stem cell trial - this one studying Prochymal for steroid refractory acute GvHD - encompassing 244 patients at 74 centers in 8 different countries (N. America & Europe). The last patient is expected to complete the trial in May 2009. MSCs have been reported as an effective agent in the treatment of GvHD by a number of medical centers. In a recent Lancet publication, Le Blanc et al. reported a 55% complete response rate when using MSCs in the treatment of steroid-resistant GvHD. Many people are watching with keen interest to see how the big questions around Osiris' BLA/MAA submissions/approval and then (hopefully) commercial issues like IP, reimbursement and product revenue models will be addressed as Osiris gets ever-closer to market.

Osiris also received approval from Health Canada to expand access to Prochymal for pediatric patients in Canada with GvHD following a similar ruling earlier this year by the FDA. Under the expanded access program, children 2 months to 17 years in age inclusive with Grades B-D acute GvHD not responsive to steroids are eligible for treatment.

Biocompatibles' CellMed treated their first stroke patient in a phase I/II trial with gene-modified, adult, allogeneic, alginate-encapsulated, MSCs dipped into the brain for 14 days (and then removed). The trial is described as the first "authorized" trial using stem cells for stroke.

In this issue of Cell Stem Cell, an ISSCR Commentary article outlines their proposed Guidelines for the Clinical Translation of Stem Cells, available in full online at the ISSCR website. The recommendations include an insistence on expert evaluation and independent oversight, a thorough informed consent process, and transparency in reporting of clinical trial results. This is aimed at all those stem cell transplant clinics selling direct to consumers with little - if any - regulatory oversight, formal clinical trials, or peer-reviewed publications.

Complementing the release of the Guidelines, in a Correspondence article, stem cell law and policy professor Tim Caulfield and colleagues published an assessment of the online portrayal of commercial stem cell transplantation retail ventures providing offshore treatments. Conclusion? They reveal most such clinics exaggerate claims and omit risks.

Organogenesis announced the receipt of two awards honoring the company's development, manufacturing and economic impact. It's been a long and twisty road for the company reinventing itself from Chapter 11 (filed in 2002) but it's certainly now the real deal and a somewhat unheralded beacon for regenmed.

On the not-so-bright side, Cell Genesys, Inc. (Nasdaq:CEGE) and Takeda Pharmaceutical Company Limited (TSE:4502) announced the termination of their collaboration agreement for the development and commercialization of GVAX Immunotherapy for prostate cancer. Takeda will return all commercial rights to GVAX immunotherapy for prostate cancer to Cell Genesys and make certain wind-down payments to Cell Genesys in connection with the phasing out of the remaining clinical development activities.

In keeping with their unique approach to life ACT has formed another ACT. Worcester biotech Advanced Cell Technology Inc. and Korean biotech CHA Biotech Co. Ltd. have formed a new stem cell technology development company called Allied Cell Technology, to be based - wherelse? - in Worcester. The international joint venture will use ACT’s hemangioblast cell technology to develop human blood cells. Allied Cell Technology will be majority owned by CHA, with ACT (OTC: ACTC) licensing its technology for a $500,000 license fee from CHA. Leading the new company in Worcester will be Young Chung, as well as Shi-Jiang Lu and the ACT hemangioblast team. Robert Lanza of ACT will serve as the chief scientific advisor of Allied Cell Technology.

Katarina LeBlanc of Karolinska Institute has been awarded a $1.2 million prize for her work in "immunological characteristics of mesenchymal cells and their use in mesencymal stem cell therapy". The prize, funded by the Tobias Foundation, will be awarded December 17.

Another wannabe cell therapy CMO takes the exit stage right - I think? WuXi-Apptec intends to close its US biologics manufacture operations to focus on testing. Chalk this up to another of several over the past handful of years who have entered - and shortly thereafter exited - the cell therapy CMO business. It's not an easy game and the true players are in it for the long-term. While they announced Wuxi-Apptec will no longer be doing "biologics manufacturing" in the US they said they are now going to focus on "cell therapy". There seems to be some confusion about what exactly that means. I guess we'll stay tuned.

Finally found a half-decent and relatively objective analysis of the recent European Patent Organization (EPO) ruling on the WARF patents sans spin.

On the gene therapy front, Ceregene reported clinical data from a double-blind, controlled Phase 2 trial of CERE-120 in 58 patients with advanced Parkinson’s disease. Regrettably the trial did not demonstrate an appreciable difference between patients treated with CERE-120 versus those in the control group. Continuing the theme, Introgen Therapeutics, Inc. (NASDAQ:INGN) announced that as part of its ongoing restructuring, the company has elected to file Chapter 11 petitions in the U.S. Bankruptcy Court. The EMEA has accepted, from Introgen's wholly-owned subsidiary in Ireland, Gendux Molecular Limited, a Marketing Authorization Application (MAA) for Introgen's ADVEXIN to treat recurrent, refractory head and neck cancer. However in September 2008, the FDA notified Introgen that the BLA was not sufficiently complete and would not be filed at that time. Demonstrating once again that success and failure are a hair's breadth apart.

HemoGenix announced the implementation of biorisk-free, green-source growth factors and cytokines for use in all HALO® Assay Kits and HALO® Contract Research Services

CBER has been busy these past few months. FDA released another new Guidance this week. This one: Guidance for Industry: Cooperative Manufacturing Arrangements for Licensed Biologics.

NovaRx Corporation appointed former CSO of Invitrogen - remember them? - Norrie J.W. Russell, Ph.D as President and COO this week. His pedigree should be invaluable as NovaRx manages the late-stage development of it lead product candidate, Lucanix(R) - a whole cell-based therapeutic vaccine comprised of four allogeneic cell lines, currenly in Phase III clinical trial for the treatment of progressive non-small cell lung cancer. Once fully open, the trial is expected to run in 90 centers in the US, Canada, Serbia, Hungary, UK, Netherlands, Germany, Poland, Italy, and India.

And finally, on the mere speculation front, yet another analyst has identified Genzyme as a ripe acquisition target by one of those cash-rich, pipeline-poor pharma's on a shopping spree.

That's the cell therapy industry as I saw it this week...

Cell Therapy HiLites 2008-11-14

Here's what caught my attention this week:

Celgene received FDA clearance to proceed with its placenta-derived stem cell clinical ttudy - a phase I, multi-center trial for moderate-to-severe Crohn's disease.

MiscroIslet filed for Chapter 11 bankruptcy protection but expects to restructure as a private company, continue operations, and file its first IND by year's end for an encapsulated porcine-islet product to treat diabetes.

Celladon released promising phase I results for the first gene therapy trial for advanced heart failure.

Cytori is starts to sell some of its StemSource® cell banking systems for collecting, processing, and storing adipose-derived cells. The company received its first order from Asian distributor Green Hospital Supply. The cell bank is to be set up in Japan. Despite all the continued skepticism about the value of cell banking to the donor-potential-patient, cell banking businesses are popping up prolifically around the world on the promise of short-term revenue to fund long-term R&D while providing a service some believe to be of irreplaceable value.

Although technically not a company-related cell therapy story, one of the more interesting developments this week was the announcement out of Charite in Berlin that they have a patient who is AIDS-free following a unique stem cell transplant. The patient developed leukemia which the docs were going to treat with a stem cell transplant. But rather than do the routine transplant by finding a match and treating just his leukemia they dared to be a little different. They went looking for a donor that matched and also had a CCR5-gene mutation (a naturally-occurring mutation which makes life difficult for the HIV virus according to some studies). The Berlin team found 80 compatible bone marrow donors for their patient, an unusually high sum, two of whom had the CCR5-Gene mutation. One of these they used with surprising and heartening results. What I like about this story almost as much as the happy ending and exciting discovery is how the doctors are trying to control the hype around this single-patient data and early results. It's not likely that this kind of transplant is a future treatmtent (for reasons related to supply, demand, and other commercial realities) but perhaps there is a kernal of a cell therapy product here somewhere that someone as innovative as these doctors will develop in time.

Ok I'm late on the draw here but it just came to my attention that in August NovaRx initiated a pivotal phase III in lung cancer patients. Watch on this blog in the coming days for more on the perception-vs-reality gap related to the number of industry-sponsored cell and gene therapy trials currently active worldwide.

Introgen may disappear while on the brink of success. Despite have an MAA being reviewed in the EU for their gene therapy for head and neck cancer, their BLA submission for the same therapy was rejected by the FDA as incomplete (currently under appeal). The company is now "exploring options" after a troubled Q3.

While not for its cell therapy program, Athersys announced it had achieved a clinical development milestone in its Bristol-Myers Squibb alliance. The amount of the milestone payment has not yet been revealed but any revenue is good revenue to offset the cell therapy development burn.

Bucking recent trends, StemCells Inc. (STEM) announced it will raise $20M in a stock sale to select institutional investors. Good news for any company in these times. Even better news for the cell therapy sector!

Finally, in the most over-reported news of the day, Pfizer opens up a regenerative medicine shop. I agree this is big news. This is not a minor investment; it's not throwing some money at a portfolio of biotechs in hopes that something will stick; it's not using stem cells as tools for drug testing or discovery. This is evidence of a belief by those in the halls of some of the tallest towers in life sciences, that cell therapies are going to change the way we treat people. Here are a couple quotes:

“Pfizer Regenerative Medicine represents a great opportunity to focus world-class research in a field that holds considerable promise for biomedical science and for the treatment of many debilitating conditions such as diabetes and neurodegenerative disorders.” said Rod MacKenzie, PhD, head of Worldwide Research at Pfizer.

The unit will be led by Chief Scientific Officer, Ruth McKernan, PhD, who said “I’m very excited to lead this new research unit. While there is still a lot to understand about how stem cells can be used therapeutically, we believe it is one of the most promising areas of scientific research.”

Ok, one more. Corey Goodman, PhD, President of Pfizer’s Biotherapeutics and Bioinnovation Center, said, “The formation of this new unit represents another key step forward in Pfizer’s commitment to be at the forefront of new approaches in biotherapeutics and bioinnovation and to expand our research efforts and expertise into emerging areas of biomedical science, like regenerative medicine, that have great potential for human health.”

Apparently the unit will operate independently (in the fashion of smaller biotechs) with about 70 researchers when fully staffed - in both Cambridge, UK and Cambridge, Mass - and work collaboratively with "leading academic, biotech and pharmaceutical partners around the world.


That's the cell therapy industry as I saw it this week. Happy weekend.