We all know someone who is battling cancer. It's a terrible disease, with over 1.6 million new cases diagnosed every year in the U.S.
Cancer deaths per 100,000 people have been slowly declining since 1991, but tragically, modern treatment often has little to offer when the cancer is already advanced or extremely deadly. Once a patient has relapsed multiple times, doctors quickly run out of options.
While the disease still claims 1,500 lives a day in the U.S., a disruptive innovation called immunotherapy may be on the cusp of changing those statistics. Immunotherapy works via an entirely different mechanism than today's go-to cancer treatments, including chemotherapy, radiation, and surgery. And thanks to remarkable recent advances in this field, we may soon be looking forward to a world with less cancer and more birthdays.
Is the cure for cancer really inside us?
For over a hundred years, medicine has been trying to boost the immune system's ability to fight cancer by activating it to recognize and repel cancer cells. But the immune system proved to be very complex, and multiple setbacks occurred, which made cancer immunotherapy's ultimate future cloudy.
And then, scientists began taking another track. Recognizing that cancer somehow turns off the immune response, the goal became to find a way to release the brakes, and turn natural defense mechanisms back on. "That was the paradigm shift in immunotherapy," says Padmanee Sharma, M.D., the director of immunotherapy at the M.D. Anderson Cancer Center.
More discoveries followed, and soon companies were dedicating increased energy to treatments that were more effective. Newer immunotherapies greatly reduced death rates, created durable responses, and offered renewed hope where not too long ago there was none. Here's a quick glance at three highly promising areas.
The PD-1 pathwayTwo recently-released immunotherapies, Opdivo from Bristol-Myers Squibb (BMY 1.11%) and Keytruda from Merck & Co. (MRK 0.79%), have shown unprecedented response rates in heavily pretreated patients for advanced melanoma, a disease that's particularly deadly.
The drugs block PD-1, a mechanism cancer cells use to escape detection by the body's immune system. Understanding the role of PD-1 inhibitors represents a huge stride forward, as these drugs appear able to reverse cancer's escape from immune recognition not only in melanoma, but also in other cancer types, such as lung, bladder, kidney, and Hodgkin lymphoma cancers, according to researchers.
Analyst Tim Anderson from Bernstein Research estimates $900 million in Keytruda sales for 2015. Wall Street has an even more aggressive target for Opdivo: $5 billion in peak annual sales within the next five to seven years. It's also worth noting, The Motley Fool's cancer specialist, Brian Orelli, Ph.D., pointed out, "In five years, the revenue from those [melanoma] patients will be overwhelmed by sales for patients who have other types of cancer."
Other companies with PD-1 candidates are working their way toward making them available, including AstraZeneca, who is in phase 3 trials for a drug that showed an amazing 46% disease control rate in a phase 1 study for patients with advanced solid tumors.
The future is one of bright promise for these drugs. As Dr. Arlene Sharpe from Harvard Medical School said, "This is creating a whole new era in cancer therapy."
CAR-T
A different immunotherapy may someday soon revolutionize the treatment of leukemia. Eight out of 10 children diagnosed with acute lymphoblastic leukemia (ALL) are cured with chemotherapy. But for children whose cancers return after intensive chemotherapy, the remaining options are "close to none," according to Stephan Grupp, M.D., who is a lead investigator of a trial testing an immunotherapy from Novartis (NVS -1.27%) for children with ALL.
The immunotherapy involves removing millions of the patient's T-Cells (a type of white blood cell) and inserting genes that enable them to kill cancer cells. The altered cells -- called CAR-T or chimeric antigen receptor cells -- are then reinfused back into the patient. If all goes well, they multiply and start destroying the cancer.
Results, thus far, have been incredible. In the recent trial, 36 out of 39 children with ALL who received the drug achieved complete remission. "When we see the response patients have...when they have few options left, it's incredibly inspiring," said Usman Azam, Novartis Pharmaceuticals' global head of its cell and gene therapies unit.
Novartis has made cancer immunotherapies one of the top priorities in its pipeline, but it has plenty of company. Just this past week, Merck & Co. announced a partnership with Intrexon (PGEN 0.71%) on a CAR-T cancer project. Shares of Intrexon shot up 9% in response.
Dendritic cell vaccines
Dendritic cell vaccines are used for both the treatment of advanced cancer as well as for prevention of cancer. The potential of these vaccines can be seen in the anecdotal example of Brad Silver, who in 2002 was diagnosed with a rare form of a brain cancer called glioblastoma, or GBM. GBM is extremely virulent. As reported by UCLA Neurosurgery, Brad Silver's case was so advanced his doctor told him he had two months to live. Brad was 33 years old, and it was supposed to be a happy time, as his wife was seven months pregnant.
As an expectant father, "I needed to find something to ... at the minimum keep me alive so I could be there for the birth of my son," Brad recalls. He joined a phase 1 trial that used a section of his tumor to create a personalized immunotherapy vaccine. Brad, who grew up surfing and lifeguarding in Huntington Beach, survived to teach his son how to surf. In fact, 11 years later, he is still celebrating his cancer-free survival.
The successful drug was developed first at UCLA, and later licensed and marketed by Northwest Therapeutics (NWBO 0.21%). As Sean Williams reported, the solid tumor drug has now been approved by the Paul Ehrlich Institute (Germany's equivalent of the FDA) to be sold to authorized German hospitals for the treatment of several forms of brain cancer, including GBM.
Another biotech working in this space is Celldex Therapeutics (CLDX 1.13%). The company's brain cancer drug Rindopepimut showed highly impressive results in three phase 2 studies against GBM and was recently awarded breakthrough designation from the FDA.
There's no guarantee either of these drugs will succeed in phase 3 trials. But GBM is a disease whose patients desperately need a new treatment option, and good news from the pipeline front could reignite the climb of these two small cap biotechs.
Research funding a challenge
Cancer is often seen as a field for specialist investors, but those willing to jump in and take risks are spurring research onward. That's particularly true because research funding is still a challenge in this field. "Somehow NCI and NIH missed the issue," says Dr. Sharma.
"Immunotherapy is a big deal. It is saving lives and it is curing people," she added. "I like using the word cure, because I don't get to use it often. NCI needs to start paying attention -- these drugs are important."
Biotechs and drug companies arepaying attention. More than 900 cancer immunotherapy clinical trials are listed on Clinicaltrials.gov. Sensational success has been offset by many failures, but still, as Dr. Stephen Hodi from Dana-Farber noted, "Even for those of us who were the biggest cheerleaders (of immunotherapy) a few years ago, it's hard to imagine that this field has moved as fast as it has."
