Genetic Engineering & Biotechnology News (GEN) featured my new article, entitled “Overcoming Phase II Attrition Problem”, on the top of Page One of its August 2009 edition.

Here is an image of Page One of the August 2009 issue.

And here am I, at the IBC Drug Discovery and Development Week conference (formerly known as DDT) in Boston, on Tuesday, August 4, holding a copy of the August issue. Thanks to Keri Dostie of IBC for taking this photo.

If you were at the conference, you may have read the article in one of the advance copies of the August GEN that were available there. Or you can look for your own copy, which you should receive in the mail shortly. More immediately, you can read the article by downloading the PDF on our website:

The article discusses the most important challenge facing the pharmaceutical industry today, the need to improve R&D productivity. It outlines leading-edge strategies for reducing pipeline attrition and for increasing the number of drugs that reach the market and that address unmet medical needs.

If you need a more in-depth exposition, you may have your company order a copy of our May 2009 book-length report, Approaches to Reducing Phase II Attrition, an Insight Pharma Report published by Cambridge Healthtech Institute (CHI). The GEN article is based in part on that report.

You may discuss issues raised by the article or the report by leaving a comment on this blog post.

Thanks are in order to those who helped make the GEN article a success. Four industry executives were quoted in the article– Charles Gombar and Evan Loh of Wyeth, Bruce H Littman of Translational Medicine Associates, and Peter Lassota of Caliper Life Sciences. (Full transcripts of interviews with these and other executives are included in an appendix to the CHI Insight Pharma report.) Drs. Littman and Lassota also reviewed the article prior to publication.

Hearty thanks also to those who served as editors of the article—Laurie Sullivan and Al Doig at CHI and John Sterling and Tamlyn Oliver at GEN. Producing a lead article for GEN (or for other publications) requires an extra level of effort from editors as well as authors, so thanks to all who participated in this effort.

Interleukin-1 beta

Interleukin-1 beta

In a blog published by Harvard Business School, Scott Anthony discussed Novartis’ R&D strategy as an example of “disruptive innovation”.

Scott Anthony is president of Innosight, an innovation consulting, training, and investment firm. Innosight’s founder, Harvard Business School professor Clayton Christensen, is the originator of the concept of “disruptive innovation”. A disruptive innovation is an innovation that improves a product or service in ways that the market does not expect. An example is desktop publishing versus traditional publishing, or the automobile versus the horse and buggy.

In his blog post (dated June 18, 2009), Mr. Anthony cites the focus of Big Pharma on developing blockbuster drugs that target the largest disease conditions. This strategy has become increasingly ineffective, due to efficacy and safety failures despite every-larger R&D budgets. In contrast, he states that Novartis is attempting to develop the most effective drugs via an understanding of the mechanisms of a disease condition, no matter how small. These effective drugs can then be tested against larger indications, and may eventually become blockbusters.

We also discuss Novartis’ R&D strategy, in our new book-length report on improving the productivity of drug development, Approaches to Reducing Phase II Attrition, published in May by Cambridge Healthtech Institute.

Novartis’ drug discovery and development strategy is based on biochemical pathways. For example, Novartis researchers note that in many cases rare familial diseases are caused by disruptions of pathways that are also involved in more common, complex diseases. The researchers therefore develop drugs that target these pathways, and obtain proof-of-concept (POC) for these drugs by first testing them in small populations of patients with the genetic disease. Drugs that have achieved POC may later be tested in larger indications that involve the same pathway.

The first drug that Novartis has been developing using this strategy is the interleukin-1β inhibitor Ilaris (canakinumab). The company conducted its first clinical trials in patients with cryopyrin-associated periodic syndromes, (CAPS), a group of rare inherited auto-inflammatory conditions that are characterized by overproduction of IL-1β. In June 2009, the FDA approved Ilaris for treatment of CAPS. Novartis is currently testing Ilaris in more common diseases in which the IL-1β pathway is thought to play a major role, including rheumatoid arthritis.

In our report, we discuss Novartis’ strategy as part of a more general discussion of biology-driven drug discovery (i.e., drug discovery based on understanding of disease mechanisms), and of other strategies to reduce pipeline attrition.

Despite Mr. Anthony’s identification of Novartis’ strategy as an example of a novel “disruptive innovation”, biology-driven drug discovery and even pathway-based drug discovery is not a new strategy. For example, most biologics (mainly developed by biotech companies, with Genentech being the best example) have been developed via biology-driven R&D. Kinase inhibitors for treatment of cancer have been developed via pathway-based strategies, often utilizing years or decades of academic research on signaling pathways in normal and cancer cells. Novartis’ Gleevec (imatinib) is an example of such a kinase inhibitor—it was the example of Gleevec that led Novartis to adopt its pathway-based strategy in the first place.

Biology-driven drug discovery and development, whether practiced by Novartis or by other companies such as Genentech, is aimed at developing effective drugs as Mr. Anthony says. Moreover, leading biologics (e.g., Avastin, Humira, Rituxan, Enbrel, Herceptin) are now on track to be the biggest-selling drugs in 2014, according to the market research firm Evaluate Pharma.

Thus biology-driven drug discovery and development has become a commercial success for many companies, not just for Novartis.

We at Haberman Associates have been advocates of biology-driven drug R&D for over a decade, long before anyone labeled it a “disruptive strategy”. Rather than being a novel, disruptive strategy, it is a fairly old strategy that most large pharmaceutical companies bypassed in favor of industrialized drug R&D based on genomics and high-throughput screening. However, the latter strategy has been generally ineffective, and Big Pharma has had to turn increasingly to biology-driven biotech companies as sources of innovative drugs. Now Novartis’ pathway-based strategy is showing considerable success in building that company’s pipeline, and Roche is integrating itself with Genentech to become a biotech company that is a member of the Biotechnology Industry Organization (BIO) rather than the Pharmaceuticals Research and Manufacturers of America (PhRMA).

The case of biology-driven drug R&D is an example of how a largely overlooked older strategy may become disruptive, when applied in the right way. Are there overlooked strategies and technologies that might become the basis of your company’s R&D success?


As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to  your company, please contact us by phone or e-mail. We also welcome your comments on this or any other article on this blog.