Next-Generation Therapeutics on the Horizon

We are seeing a significant shift in the kind of medical therapies that are reaching the market. Biotechnology companies are leading the charge with innovations and drug prospects—especially molecular diagnostics and therapeutic biologics. The shift is driving Big Pharma to source and acquire this innovation and thereby fill their product-pipeline gaps, which are growing as blockbuster drugs lose their patent protection.

In the next few years, top-selling small-molecule drugs such as Pfizer's Lipitor and sanofi-aventis/Bristol-Myers Squibb's Plavix will be replaced by an emerging wave of proteins and biologics, including Roche/Genentech's cancer therapy Avastin and Amgen's fully human monoclonal antibody (mAb) denosumab, reflecting the growing commercial dominance of injectable biotechnology drugs, especially for cancer and rheumatoid arthritis.

The convergence of pharmacogenomics and biologics—and our understanding about how they work at the molecular level—has in large part changed the landscape of biopharmaceuticals. Completion of the Human Genome Project in 2003 has been a major driver of biomedical discovery, and the pace continues to accelerate. Although predictions about the dawn of a new era of molecular and personalized medicine were premature, a great deal has been achieved. Powerful new drugs have been developed for some cancers, genetic tests can predict whether people with breast cancer need chemotherapy, the major risk factors for macular degeneration have been identified, and drug response can be predicted accurately for more than a dozen drugs. If nothing else, our newfound genomics knowledge has shown just how complex diseases are. In the next decade, we can build on what we have learned to deliver more individualized treatments for patients. However, the promise of new genomic technologies and their positive effect on human health remains quite real.

The biotechnology industry has proved itself over the years by developing novel antibody-based therapeutics. The sector has expanded therapeutic applications through engineering breakthroughs and computational initiatives. Novel designs are creating therapeutic antibodies that minimize unwanted properties while improving specificity and half life. mAbs are certainly emerging as one of the major classes of therapeutic agents in the treatment of human diseases, specifically in cancer and immunological disorders. In addition to the mAbs that have been approved in the US, hundreds more are being developed clinically by bio/pharmaceutical companies. These next-generation antibody-based therapeutics will be the medicines of the future.

Another promising line of inquiry revolves around RNA interference (RNAi) — a naturally occurring cellular mechanism for silencing gene expression. Discovered by Andrew Fire and Craig Mello in 1998, RNAi exploits the ability of small fragments of RNA, known as small interfering RNAs (siRNAs) to block, or interfere with, the production of specific genes for therapeutic purposes. Their discovery promises to be the third great advance in biotechnology after gene cloning and mAbs. The siRNAs have advantages over traditional small-molecule drugs and antibodies in that they have the potential to halt disease processes that are untouchable by existing biotechnology drugs or conventional small-molecule pills. In addition, siRNAs can serve as a platform for a new class of therapeutics.

There has been great excitement among industry about the technology, and already siRNAs have advanced into clinical trials just six years after their discovery. The pharmaceutical industry has made major investments in RNAi technology. Alnylam Pharmaceuticals, for example, made big news in July 2007 when Roche paid $331 million upfront, and agreed to pay more than $1 billion over time, for nonexclusive access to use Alnylam's RNAi technology to develop drugs for cancer, respiratory diseases, metabolic disorders, and certain liver conditions. Although Roche recently announced that it was terminating its efforts to discover and develop drugs through RNAi, the field remains one to watch in the future.

Another technology gaining a new lease on life is the cancer vaccine, especially following the approval of Dendreon's prostate cancer vaccine Provenge in April 2010. According to research reports, the areas expected to display the highest levels of activity and development include vaccines for melanoma, lymphoma, cervical, renal, and prostate cancer. Many of these products are already in Phase III development and have orphan-drug, special protocol assessment, or fast-track status. Their potential approval indicates a promising future.

G. Steven Burrill is CEO of Burrill and Company, steve@b-c.com, www.burrillreport.com.