Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology & Hematology

Posts tagged ‘New Products’

Nanotechnology is set to have a major impact on drug development and new products for the diagnosis and treatment of cancer.  Research from UCSF and Northwestern University published earlier this year in “Science Translational Medicine” shows this potential.

Edward Chow and colleagues describe how binding the cancer chemotherapy doxorubicin (DOX) to carbon nanoparticles 2-8nm in diameter in the form of a diamond, “nanodiamond” (ND), improved drug efficacy and overcame drug resistance.  Although this pre-clinical animal research has not yet been confirmed in humans, it raises the possibility of more efficient chemotherapies and the hope of increased survival rates as a result.

The conclusion from this research is that nanodiamonds may be a viable drug delivery platform for small molecules, proteins and nucleic acids. This technology could have an application in wide range of diseases.

Why is nanoparticle-mediated drug delivery more effective? The paper suggests one reason is that the nanodiamond-doxorubicin complex (NDX) allows for a more gradual release of DOX, allowing for increased tumor retention and increased circulation time.

It’s important to note that the NDX complex does not specifically target the drug efflux pumps, such as MDR1 and ABCG2 transporter proteins, responsible for chemoresistance. Instead the NDX complex appears to overcome drug resistance passively by the way DOX is released from the nanodiamond.

This research shows that taking old drugs and combining them with new drug delivery technology may offer therapeutic benefits.  The authors conclude that this research, “serves as a promising foundation for continued NDX development and potential clinical application.”

If successful in humans, it will translate into new product development and market opportunities for emerging biotechnology and biopharmaceutical companies.


ResearchBlogging.orgChow, E., Zhang, X., Chen, M., Lam, R., Robinson, E., Huang, H., Schaffer, D., Osawa, E., Goga, A., & Ho, D. (2011). Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment Science Translational Medicine, 3 (73), 73-73 DOI: 10.1126/scitranslmed.3001713

Following on from my recent blog post on emerging treatments in osteoporosis, one of new approaches in development is the inhibition of cathepsin-K.

Cathepsin-K inhibition is a novel approach to osteoporosis treatment and Merck’s odanacatib is leading the way in this new class of drugs. It is currently in phase III development, with 16,716 subjects enrolled (NCT00529373).

Cathepsins are lysosomal proteases. Cathepsin K (Cat-K) is a cysteine protease that plays an important role in the function of osteoclasts (the cells responsible for bone destruction). Cat-K acts to degrade bone collagen. By inhibiting it, the removal of bone matrix proteins by osteoclasts is reduced.

However, Cat-K inhibitors such as odanacatib do not kill off the osteoclast, but allow it to still produce chemokines and growth factors such as WNT that are responsible for the effective function of osteoblasts (the cells responsible for bone formation).

The net result is that Cat-K inhibitors reduce bone resorption.

Phase II clinical trial results for odanacatib presented at the American Society of Bone and Mineral Research (ASBMR) annual meeting last year (abstract #1247),  showed an increase in spine and hip bone mineral density (BMD) after four years of follow-up, suggesting that odanacatib use leads to increased bone strength. As reported by Merck in their press release:

In postmenopausal women who received odanacatib 50 mg weekly for four years (N=13), an increase in BMD of 2.8 percent at the lumbar, and 2.7 percent at the hip were demonstrated between years three and four of treatment. Over four years of treatment, these women had increases in lumbar spine (10.7 percent) and hip (8.3 percent) BMD from baseline.

If you are looking for further information on the science, the February 2011 issue of “The Journal of Bone and Mineral Research” has several papers on odanacatib, osteocytes and cathepsin K inhibitors.

Merck has 16,716 subjects enrolled in their phase III trial for odanacatib, and July 2012 is indicated as the date when data will be available for the primary end-point of reduction in fracture risk over the three year treatment period.  We can expect the phase III results shortly after that, and if positive, an FDA approval could be expected in 2013.

The development of odanacatib by Merck is clearly a strategy to combat generic alendronate, which has eroded Merck’s market share and profits for Fosamax.  Both odanacatib and generic alendronate, are once weekly doses. The timeline for a product launch for odanacatib appears to be in the late 2013/2014 period, and I am sure further clarity on this will appear from Merck nearer the time.

The challenge for odanacatib is that by 2015, analysts estimate that Amgen’s RANKL inhibitor denosumab will be a blockbuster (more than $1 billion in sales) and sales of parathyroid hormone analogues will have tripled to $1.4 billion.

Although the market opportunity in osteoporosis is likely to grow given the aging population around the world, it remains to be seen how the cost/benefit of odanacatib will stack up against the competition, and whether Merck can capitalize on this.

After I wrote my previous blog post about the emerging biotechnology region around Austin, TX, one of the comments I received was about the importance of networking opportunities within a cluster or region.

So I am pleased to have been invited to a medical technology-life science networking event in New York City (NYC) organized six times a year by Ted King of Saddlerock Advisors, Wendy Brown of Merrill Lynch and John Lieberman of Perelson Weiner.

The event, later today, has a format of a featured speaker and presentations by three emerging companies that provides them with the opportunity to network and showcase their technology, new drugs or medical devices to investors, industry partners, academics and researchers.

This evening there is a presentation on the proposed changes to the FDA’s 510(k) clearance process for medical device approval.  This is the route by which the majority of medical devices come to market by showing they are comparable to an existing approved or marketed product.

The three featured companies include BioView (an Israeli technology company involved in cell imaging and automation of genetic testing), Cel-Sci (a Virginia based biotech company that has as immunotherapy product in development about to enter a global phase III clinical trial in head and neck cancer) and PatienTech (a company that develops elastic-sheet, pressure sensing systems that can be used with medical devices).

It will be interesting to see who attends, and whether the presentations by the companies are what I consider to be the typical investor “puff and fluff” presentations, or whether there is any meaningful discussion of science, marketing strategy and new product development.

Last week on January 20, 2011, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee decided not to recommend approval of Lilly’s Amyvid™ (florbetapir) in a 13:3 vote.  Florbetapir is an imaging agent used with Positron Emission Tomography (PET) to show accumulation of beta-amyloid plaque in the brain. I previously wrote about Lilly’s acquisition of Avid Radiopharmaceuticals for florbetapir on this blog.

This imaging approach aids in the early detection of Alzheimer’s disease, as a negative scan, not showing any beta-amyloid plaque, would rule out Alzheimer’s disease.  Given that it is currently, hard to distinguish age related memory less and different types of dementia, diagnostic imaging tools have an important role to play.

The FDA advisory committee’s decision would probably have come as a surprise to Lilly, since the clinical trial data showed clear efficacy and no safety concerns.  While the committee rejected immediate approval, they did recommend approval (16:0), conditional on a training program to show that radiologists and readers of the scans could be accurate and consistent in their image interpretation. The FDA is not bound by the Committee’s recommendations but is required to take them into consideration when deciding whether to grant approval.

Imaging is becoming increasingly important in clinical trial design. In therapeutic areas such as osteoporosis, rheumatoid arthritis and oncology, imaging end points are often surrogates for drug efficacy.

The challenge that emerging biotechnology companies face in linking imaging to drug use, is the variability of readers outside a controlled clinical trial environment where images may be read centrally.  Standardization of image acquisition and reading needs to take place, so that a radiologist in different hospitals can come up with the same findings.  Those involved with imaging clinical trials know how hard this can be, even within the controlled clinical trial setting.

The recommendation of the FDA advisory committee that Lilly needs to put in place a training program to show accuracy and consistency of readers is a valid concern and one that all biotechnology companies and pharmaceutical companies should take note of when developing imaging agents.

A conference on Innovation in Healthcare is being held in Cambridge, MA on Tuesday, February 1, 2011.

The speaker list is impressive and includes Michael Porter (Porter’s 5 forces model is well known to all MBA students), John Mendelsohn (President of MD Anderson), Janet Woodcock (Director of Center for Drug Evaluation and Research at FDA) and Peter Senge (author of the Fifth Discipline: The art and practice of the learning organization).

The symposium, whose lead sponsor is Merrimack Pharmaceuticals, will discuss how to to improve the system for delivering healthcare services, and how to increase the productivity of translating biomedical research into medical innovation.  The conference certainly has ambitious goals in the topics it plans to cover!

Innovation to me is about adding value, whether that be in the delivery of a service or the development of a new product by a biotechnology company.  If you are in the Boston area on February 1, this one day symposium at MIT looks well worth attending, and the registration fee is inexpensive ($50).

One of the exciting things about the biotechnology industry is its ability to innovate and translate developments in basic science into potential new drugs.

I previously wrote about denufosol in cystic fibrosis (CF), a disease that affects about 30,000 people in the United States and 70,000 worldwide.  The disease is characterized by the accumulation of mucus that leads to bacterial overgrowth and chronic lung infections. Mucus cannot be removed from the lung in CF due to abnormal mucociliary transport resulting from impaired epithelial chloride secretion and sodium hyperabsorption.  This is now known to be due to defective cystic fibrosis transmembrane regulator (CFTR) protein. A good overview of this can be found in the 2006 New England Journal of Medicine Editorial by Felix Ratjen, “Restoring Airway Surface Liquid in Cystic Fibrosis.”

A good overview of the pipeline of new drugs in development for CF can be found on the Cystic Fibrosis Foundation web site.  Vertex in particular has two drugs  (VX-809, VX-770) in late stage development that are cystic fibrosis transmembrane conductance regulators, aimed at increasing CFTR function.  Phase 3 registration data for VX-770 is expected in the first half of 2011. I look forward to writing about the results.

Recently, a team from Johns Hopkins led by Neeraj Vij published a paper in the January 2011 issue of Journal of Immunology on the “Critical Modifier Role of Membrane-Cystic Fibrosis Transmembrane Conductance Regulator-Dependent Ceramide Signaling in Lung Injury & Emphysema.”

The researchers found that lung damage in mice was associated with changes in the amount of CFTR in the cell surface membrane.  Decreases in the amount of CFTR were associated with increased ceramide, a trigger of inflammation of cell-death. Or as the the paper describes it:

“CFTR expression inversely correlates with severity of emphysema and ceramide accumulation in chronic obstructive pulmonary disease subjects compared with control subjects.”

The emergence of inflammation as a key role in chronic disease was the subject of a previous blog post about diabetes, so is interesting to see another area where it is involved.

This basic research shows that developing drugs that target CFTR and mediate ceramide may have an important role to play in the treatment of emphysema, a chronic obstructive pulmonary disease (COPD) that affects 2 million Americans.  Translational medicine that can take basic science and apply it to clinical practice is key to the long term success of the biotechnology industry.

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Thanks to Adam Feuerstein of TheStreet for breaking the news this morning, that shares in Inspire Pharmaceuticals (NASDAQ: ISPH) have plunged following the announcement of negative data from the phase 3, TIGER-2 clinical trial for denufosol in cystic fibrosis.

According to the Chief Medical Officer at Inspire Pharma: “The analysis of the primary endpoint, key secondary endpoints and select subgroup populations in TIGER-2 indicates an absence of meaningful treatment benefit in this patient population.

I wrote a blog post last week about denufosol and the hope that this drug offered to cystic fibrosis patients despite the uncertainty about its clinical effectiveness.

The latest data is disappointing and a major setback to Inspire Pharma. It highlights the risk/reward situation that many emerging biotechnology companies face with new product development, the hope that they will make it to market, coupled with the reality that many will fail.

World Intellectual Property Organization LogoIntellectual property (IP) rights are important in the biotechnology industry; one only has to look at a licensing, consulting or service agreement to appreciate this.

If you are a non-lawyer new to the area, and wish to gain a basic understanding of the different types of intellectual property protection such as copyright, trademarks, industrial design, patents and unfair competition, then the World Intellectual Property Organization (WIPO) Academy offers a free general course (DL-101).

The course is delivered online, twice a year, over 6 weeks.  If you are a native English speaker, it takes far less time to complete than the 50 hours suggested.  What makes the course work well is you can download the study material as PDF files. These can then be read anywhere – I used my kindle.

An additional benefit, if you have an ego wall in your den or office, is that WIPO send you a certificate after you pass a final exam.  When I lived in the UK, I put all my certificates on the wall in the downstairs toilet,  an idea I “borrowed” from Mrs Thatcher’s eye surgeon when I had dinner at his home. British understatement at its best.

Although the WIPO general course is not focused on biotechnology or the life sciences industry, it does provide a useful overview of international treaties and IP regulation to build upon.  It is worth considering if you are new to the area.

With best wishes for the New Year, may it bring you good health, happiness and prosperity.

Inspire Pharmaceuticals (NASDAQ:ISPH), a North Carolina based biopharmaceutical company that focuses on products for ophthalmic and pulmonary diseases, recently announced positive results from their phase 3 trial (TIGER-1) of denufosol tetrasodium in patients with Cystic Fibrosis (CF).

Cystic Fibrosis is a genetic disorder that can lead to death as a result of pulmonary complications from airway obstruction, bronchial thickening and accumulation of mucous.  Lung function tests are widely used in the diagnosis, treatment and management of patients with CF.  Measurement of FEV1 (Forced Expiratory Volume in 1 second) is regarded as the best predicator of mortality.  As the disease progresses and the lungs become more obstructed, FEV1 decreases.

Inspire Pharma’s denufosol is an ion-channel regulator that helps keep the airways moist and helps mucous removal in CF patients.  It increases chloride secretion via calcium-activated chloride  channels (CaCCs), inhibits sodium absorption via epithelial sodium channels (ENaCs) and stimulates ciliary beat frequency.  Conveniently for patients, it is being developed as an inhaled drug delivered direct to the lungs by nebulizer.

The phase 3 clinical trial data presented by Dr Frank Accurso at the Annual North American Cystic Fibrosis Conference, and in the paper published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM), showed an improvement in lung function after 24 weeks in patients with mild CF who received daily denusofol by means of a nebulizer.  The primary efficacy endpoint was a change in FEV1:

Source: October 21, 2010 presentation by Frank J. Accurso M.D. to North American Cystic Fibrosis Conference.  Available at Inspire Pharma.

Dr Accurso and his colleagues reported that the results demonstrated:

“Mean change from baseline to Week 24 endpoint in expiratory volume at 1 second (primary efficacy endpoint) was 0.048 L for denufosol (n=178) and 0.003 L for placebo (n=174; P=0.047).”

Despite the significant improvement in FEV1, there was no significant difference between the denufosol and placebo arms in the time to progression to first pulmonary exacerbation, suggesting that its long-term clinical effectiveness remains uncertain.

Source: October 21, 2010 presentation by Frank J. Accurso M.D. to North American Cystic Fibrosis Conference.  Available at Inspire Pharma.

Notwithstanding, these results do offer hope to patients with mild symptoms of Cystic Fibrosis.  Early treatment to maintain lung function may delay the onset of more severe physiological changes and the need for more radical treatment options such as a heart/lung transplant.

Thanks to BBC Health for writing about this topic and giving me the idea for this post.

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