BioScience Biz

Clinical research activity up significantly in 2008

According to a report in FierceBiotech, surprising news came out of the recently completed 45th Annual Meeting of the Drug Information Association (DIA).  Despite cutbacks in the international biopharma industry, clinical trial activity was up in 2008. Overall, 795 new clinical trials were launched in 2008, compared with 662 that were initiated in 2007. There were 5,700 active INDs in 2008, which represents a greater than 20 percent increase over the 4,744 INDs active by the end of 2007—a substantial increase.

Trial activity was also assessed by the number of new FDA form 1572s, which all clinical investigators on FDA-approved trials sign as a promise that he will abide by the federal guidelines set forth in the Code of Federal Regulations for the use of drugs in an investigational setting. The FDA registered 23,827 new 1572s from clinical investigators in 2008, up 5.8 percent from the previous year. However, the number of new 1572s from China-based clinical investigators fell 30 percent due to the long approval process, but Indian-based 1572s rose 14 percent. South Korean investigators submitted 74 percent more 1572s while submissions from Taiwan rose 21 percent. Clinical trial activity is also up in Eastern Europe where the FDA saw significant increases from Russian investigators (20 percent), as well as Romanian (44 percent), Polish (17 percent) and Bulgarian (57 percent) clinical researchers.

It will be interesting to see the data for 2009.

DIA is a professional association of more than 18,000 members worldwide who are involved in the discovery, development, regulation, surveillance, or marketing of pharmaceutical products. The DIA annual meeting is the biopharmaceutical industry's largest, longest running, international event.  

More stem cell trial problems for Osiris Therapeutics

Clinical trials can be vexing, just ask anyone associated with Osiris Therapeutics, a leading stem cell therapeutic company. The company recently announced that their mid-stage, Phase II trials to treat chronic obstructive pulmonary disease (COPD) with adult stem cells (called Prochymal) did a great job reducing inflammation, but failed to improve pulmonary function. The 62 patients enrolled in the trial will be followed for two years in order to assess possible long term effects of the therapy.  Nevertheless, these results reveal how complicated and unpredictable clinical trials can be. 

COPD is really a combination of two maladies, chronic bronchitis and emphysema, rolled into one diagnosis. The disease commonly is caused by smoking, which triggers an abnormal inflammatory response in the lung in some individuals. In the larger airways, this inflammation causes chronic bronchitis, while in the microscopic lung sacks called alveoli, the inflammatory response causes emphysema, which is the destruction of the lung tissues where oxygen and carbon dioxide are exchanged. The result of this double inflammatory whammy is to limit the flow of air to and from the lungs causing shortness of breath. COPD is poorly reversible and usually gets progressively worse over time. In 1990, COPD was the third leading cause of death worldwide.

"...anyone would have predicted a priori that reducing lung inflammation would translate to improved lung function."

Given the central role of inflammation in the pathogenesis of COPD, anyone would have predicted a priori that reducing lung inflammation would translate to improved lung function.  But, this is like believing that the baseball team with the most hits will automatically win the game. It is not uncommon for such surrogate measurements of efficacy to fail to predict the final outcome—the full game must still be played and the clinical trial done before the outcome can be certain. 

Osiris is also testing Prochymal for its ability to treat other inflammatory diseases, so the reduced inflammation seeing in the COPD trial might be a good omen for these other maladies, even if Prochymal is of little benefit to patients with COPD. Unfortunately, however, last month Osiris was forced to discontinue enrollment in a phase III trial to treat the chronic inflammatory bowel condition known as Crohn’s disease. The reason for this, according to the company, is that patients on the placebo arm of the trial were doing unexpectedly well and interim data analysis indicated that this response would make it impossible to show a benefit of the Prochymal therapy. After examining the data with the FDA, it was concluded that  that there was a potential “systematic design flaw” in the trial that “might be related to the fact that patients responding to the initial stem cell therapy were eligible to participate in a second, longer-term trial evaluating Prochymal as a maintenance therapy. Because the current standard for determining response of Crohn's patients to therapy is largely subjective, there may have been response bias to meet the eligibility requirements for continuation of therapy in the longer-term maintenance trial”.

Prochymal is a preparation of mesenchymal stem cells obtained from the bone marrow of healthy donors and specially formulated for intravenous infusion. In addition to Crohn’s disease, Prochymal also is being tested in two other Phase III studies to treat both acute and steroid-refractory graft-vs-host diseases (or GvHD). The FDA granted Prochymal Fast Track status for these and Crohn’s diseases and both the FDA and the European Medicines Agency granted Prochymal Orphan Drug status for GvHD. In addition to the COPD trail, Osiris is also conducting Phase II Prochymal trials for the treatment of acute myocardial infarction and type 1 diabetes.  The therapy also is being developed as a potential treatment for acute radiation syndrome.

"...the company has a lot riding on Prochymal and can ill afford any further
clinical trial snafus." 

Osiris also has another stem cell product in the pipeline, called Chrondrogen, which is being tested for its ability to regenerate cartilage. Last November, Genzyme paid Osiris $130 million upfront and promised up to $1.3 billion more in milestone and other payments to gain commercialization rights to Prochymal and Chondrogen outside the U.S. Osiris retains the rights to market these products in North America.  Clearly, the company has a lot riding on Prochymal and can ill afford any further clinical trial snafus. 
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© 2009 Steven S. Clark, PhD, some rights reserved.  Articles contained herein, are meant to be distributed freely to interested parties. However, any use, including excerpts from any article, must credit Steven S. Clark and provide a link to the original article published in BioScience Biz.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, neither Steven S. Clark, nor other authors, assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

Slicing and Dicing SBIR Award Data

If you like numbers and acronyms, you will like this article. SSTI (State Science and Technology Institute), a national nonprofit network of practitioners and policymakers dedicated to improving the economy through science and technology, recently published SBIR Phase I proposal and award statistics by state for 2008. They also have similar data going back a few years. Being an Excel addict, I copied and pasted the data into a spreadsheet and was able to parse interesting tidbits from the larger meal of information. For instance, in 2008 the overall success rate for all Phase I SBIRs was just under 17%, somewhat better than research grant success rates at most NIH institutes, with which I am painfully familiar. The percentage of SBIR applications that were awarded ranged from a low of 9.4% at the DoT to a high of 24.1% at the NIH (more than twice the rate of RO1 investigator-initiated research grants in 2008).  Other agencies awarded grants at the following rates: DHS (9.6%), DoD (14.9%), NSF (15.4%), USDA (17.4%), NASA (18.4%), and DoE (18.7%). The raw data can be found on the SSTI web site.

Also interesting is the total number of SBIR grants awarded by the different agencies. In 2008 a grand total of 3555 Phase I awards were made by all participating federal agencies.  By far, the DoD made the most awards at 1825, more than half the total number of awards.  Trailing way behind were NIH (739 awards), DoE (280), NASA (276), NSF (224), USDA (77), DHS (28) and EPA (25).  Other agencies, such as NOAA, are not included here because they awarded so few SBIR grants they had minimal impact on these analyses.

State-by-state data

As I played with the spreadsheet and filtered the data in different ways, I learned a few other things. The top ten states with the most awards are the following in descending order and with the total number of awards in parentheses: California (688), Massachusetts (476), Virginia (224), New York (195), Colorado (182), Maryland (156), Texas (140), Pennsylvania (129), Ohio (120) and Florida (102). Wisconsin came in at a mediocre number 24 with a total of only 37 awards in 2008.

"...SBIR success pretty much follows Big 10 football and basketball success..."

If these data are taken as a measure of the success by which each state translates new technology into business, then Wisconsin (#24) is well behind Michigan (#12), Alabama (#13) and even New Mexico (#14). Illinois comes in at #18 and Minnesota at #22.  Compared to other Big 10 states, Wisconsin is just ahead of Indiana #25.  Iowa trails at #35. If you think about it, SBIR success pretty much follows Big 10 football and basketball success with Michigan and Ohio on top, while Wisconsin is in the second tier with Minnesota, Illinois and Indiana.  A cynical observer might conclude that sports success predicts technology business success. But, that seems to only work in the Big 10, since Massachusetts, with no sports powerhouses, is in the top two of SBIR grant winners from almost all agencies (more on that below).

At face value it may be surprising that states like New Mexico and Alabama are more successful than Wisconsin at winning SBIR grants (ok, so New Mexico also kills my sport’s success analogy).  And these states are consistently more successful than Wisconsin at winning SBIR grants.  From 2005-2008 Alabama won 103, 79, 72 and 73 grants—a declining trend. During the same period, New Mexico SBIR awards were more constant with an uptick in 2008, numbering 57, 60, 56 and 67. In contrast, Wisconsin enjoyed an upward trend from 2005-2007 with a downtick in 2008, with 36, 42, 49 and 37 SBIR awards, respectively. But, the reality that Alabama and New Mexico are more successful than Wisconsin in this regard needs to be tempered by the fact that different states focus on different technologies and may be more competitive in different areas. For instance, in Wisconsin, the number of SBIR awards from each federal agency in 2008, with the success rate in parentheses, is as follows: 1 award from NSF (6.7% success), 1 from USDA—surprising for an ag state,  (8.3%), 10 from DoD (14.7%), 2 from NASA (11.8%), 20 from NIH (29%), 2 from DOE (13.3%). Wisconsin is trending up in NIH supported SBIRs with 13, 19, 22, and 20 grants over the years 2005-2008.  Over the same period, DoD grants were fairly consistent in Wisconsin, numbering 8, 10, 13 and 10. Clearly, Wisconsin is spinning out more life science related tech business than technology business from other industries, with defense-related technology business springing up at about half the rate of biotech business.

Compare Wisconsin’s strong emphasis on life sciences to what is happening in Alabama and New Mexico. Alabama’s 2008 SBIR portfolio is as follows: 2 grants from USDA (40% success rate), 56 from DoD (16.7% success), 4 from NASA (10%), 7 from NIH (18.4%), 4 from DOE (30.8%).  Clearly Alabama focuses on defense and lags behind Wisconsin in biotechnology transfer.

In 2008 New Mexico also focused on defense as well as space and energy related technology transfer. This state won the following SBIR grants: 5 awards from NSF (19.2% success rate), 2 from USDA (40%), 1 from DOT (50%), 24 from DoD (14%), 13 from NASA (32.5%), 5 from NIH (14.7%), 14 from DoE (41.2%).  The state has consistently done well with energy grants since 2005, but the NASA grants awarded in 2008 represents a 2-3 fold jump from previous years.

One take home message from these analyses is that if you are an engineer or chemist, go to New Mexico, if you are a biologist, Wisconsin is a better place to find a job.

Room to improve in Wisconsin

Clearly, in 2008, biotech was the strength of WI SBIR success—with more NIH SBIR awards than awards from all other agencies combined. Wisconsin was 11th in the country in the number of NIH SBIR grants, behind the usual suspects. The top 10 in order were, CA, MA, MD, NY, TX, NC, PA, CO. MI and WA. But after CA (140 biotech SBIR grants) and MA (with 103), which together won 33% of all the NIH SBIR grants, there is a sharp drop in the number of SBIRs awarded by NIH. For, instance, coming in at number three, MD only won 43 SBIR grants from NIH. So, Wisconsin, while ranking near the top 80th percentile for NIH awards with 20 grants, is further behind the leaders than its ranking suggests. 

"...investment in quality research universities pays large dividends
in developing technology businesses..."

Interestingly, CA and MA are also in the top two for NSF, DoD, NASA, and DoE SBIR awards. It is no accident that many of the elite research universities in the US are found in these states and it is these academic elites that feed the new technology pipeline that leads to new business development. Together, these data point to the reality that investment in quality research universities pays large dividends in developing technology businesses—a lesson that Wisconsin cannot afford to forget, but sometimes tries to forget. This state has one elite research university and it pays huge dividends.  Without the UW-Madison, which spins off the lion’s share of biotech and health related (and other) technologies, we would be much farther down the line spinning out new technology businesses.  One question is how can the state get the UW-Milwaukee, Medical College of Wisconsin, Marshfield Clinic and other institutions to move up in R&D status to help make Wisconsin more competitive in generating life science technology businesses? Another question is what would it take to make Wisconsin more successful in translating engineering, energy, defense and agricultural technology into state businesses.

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© 2009 Steven S. Clark, PhD, some rights reserved.  Articles contained herein, are meant to be distributed freely to interested parties. However, any use, including excerpts from any article, must credit Steven S. Clark and provide a link to the original article published in BioScience Biz.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, neither Steven S. Clark, nor other authors, assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.