Breast cancer is the second leading cause of cancer deaths among women, falling second only to lung cancer. Fortunately, the mortality rate has steadily declined since 1989, partly because of earlier detection through regular screenings and improved treatment options. Pharmaceuticals, in particular, took a major leap forward with the approval of Roche's (NASDAQOTH:RHHBY) monoclonal antibody Herceptin in 1998 for metastatic HER2-positive breast cancer. In many ways, Herceptin's approval marked the beginning of the age of personalized medicine and a focus on more targeted cancer therapies with fewer side effects. Since then, biotechs far and wide have raced to develop the next generation of breast cancer treatments, and this herculean task is only now beginning to bear fruit, nearly 16 years after Herceptin's initial approval by the Food and Drug Administration.
Because the breast cancer drug market is expected to grow to $24 billion by 2016, these next-generation therapies could provide some compelling investment opportunities. With that in mind, let's take a closer look at some of the most intriguing new drugs and clinical candidates being developed by Celldex Therapeutics (NASDAQ:CLDX), Eli Lilly (NYSE:LLY), Pfizer (NYSE:PFE), Novartis AG (NYSE:NVS), and Roche.
Spurred by their blockbuster success with Herceptin, Roche and its subsidiary Genentech have worked diligently to bring other monoclonal antibodies to bear in the fight against breast cancer, culminating in the FDA approval of Perjeta in 2012. Perjeta is a HER2 dimerization inhibitor used in conjunction with Herceptin and docetaxel for the treatment of metastatic HER2-positive breast cancer and as a neoadjuvant treatment for early stage breast cancer. Analysts believe Perjeta could see peak sales of an eye-popping $8.5 billion by 2020 if the drug can gain a handful of additional approvals. Per its current approvals, Perjeta is still expected to be a blockbuster in its own right, with peak sales forecast by some to hit as high as $2.5 billion.
Taking the targeted therapeutic approach one step further, antibody-drug conjugates combine an antibody with a potent cytotoxin through "linker technology." Although the broad commercialization of ADC's has been hampered by toxicity issues, the FDA approved Roche's Kadcyla last year as a treatment for late-stage breast cancer patients that have stopped responding to Herceptin and chemotherapy. Kadcyla is Herceptin combined with the cytotoxin DM1 via linker technology and used as a treatment of last resort for late-stage breast cancer. Despite the drug's problematic side effect profile, clinical studies showed that patients receiving Kadcyla lived significant longer than patients on standard therapy. What's particularly interesting from an investment standpoint is that Kadcyla could achieve peak sales as high as between $2 billion and $5 billion, even though it's indicated for a relatively small patient population.
Celldex Therapeutics is also developing an intriguing ADC called CDX-011 for triple-negative breast cancer. In a mid-stage study, some patients receiving the drug had their tumors shrink and survived nearly twice as long as patients on standard therapies. Celldex is expected to open further clinical sites in the U.S., Canada, and Australia this year, with the study possibly concluding in 2016.
CDK 4/6 dual inhibitors
Small molecule drugs aimed at inhibiting CDK 4/6 to stop the growth of cancer cells have also seen a flurry of clinical activity in recent years. Although no CDK inhibitors have been approved for the treatment of cancer yet, Pfizer, Eli Lilly, and Novartis all have CDK inhibitors under development. Among these companies, Pfizer appears to be the closest to a regulatory approval with its drug palbociclib. Palbociclib is presently being studied as a potential treatment for advanced breast cancer, with Pfizer reportedly considering accelerated approval for the drug based on mid-stage results. At the American Association for Cancer Research meeting in San Diego last weekend, Pfizer said that progression-free survival for patients receiving the drug nearly doubled to 20.2 months compared to patients on standard therapy, but the study has yet to show a clinical benefit in terms of overall survival.
Novartis also has a rival CDK inhibitor in a late-stage trial called LEE011 and Eli Lilly has an early-stage candidate known as LY2835219. Analysts believe the first FDA approved CDK inhibitor for breast cancer could see peak sales of anywhere between $1 billion to $9 billion, depending upon the effectiveness and safety profile of the drug.
The economics of breast cancer pharmacotherapy are staggering, with multiple megablockbusters already on the market. Even so, the diversity of breast cancer types lacking approved therapies, other than cytotoxins, shows there is still a large unmet medical need. And while Pfizer's palbociclib could be the next megablockbuster breast cancer drug to help fill this void, there will certainly be others in the near term, evinced by Celldex's and Novartis' rapid clinical development of their respective drugs. So, you may want to dig deeper into these leaders in the race to develop the next generation of breast cancer medications.