Cancer Immunotherapy: The Breakthrough of 2013

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As we bid farewell to 2013 and think about where we've been, where we are, and where we're going, it's clear that we're in the midst of a great transformation in the treatment of cancer. With biologic drugs representing some of the most lucrative therapies in history and a burgeoning understanding of the cellular basis for cancer, it's no surprise that Science magazine has named cancer immunotherapy as 2013's Breakthrough of the Year. In fact, this new era in biotechnology has drawn some of the biggest names in health care, like Merck (NYSE: MRK  ) , Roche (NASDAQOTH: RHHBY  ) , and Bristol-Myers Squibb (NYSE: BMY  ) , to develop their own immune-stimulating cancer fighters. Let's dig deeper into this exciting field that represents a triumph for scientists and a new hope for patients.

What is immunotherapy?
Cancer cells are fundamentally different than other cells in their ability to replicate uncontrollably and fend off the watchful eye of immune cells trained to gobble them up. The goal of immunotherapy is to tip the scale in favor of the immune system to fight off tumor cells without dumping traditional toxic chemotherapy into the patient. There appear to be two ways to do that: turn the immune system on, or train the immune system to specifically battle tumor cells that it otherwise might have ignored. Both approaches seem to work in clinical trials, and there are some exciting drugs in each class worthy of a closer look.

Checkpoint inhibitors
The immune system is extremely tightly regulated. Too active and you get autoimmune disorders; too quiescent and the common cold can be deadly. Some tumor cells have a Programmed Cell Death Ligand, or PDL-1, that tells Programmed Cell Death Receptors, or PD-1 receptors, on immune cells to shut down. Antibodies designed to bind to either of those proteins keep immune cells on high alert and have been useful in treating cancer.

Bristol-Myers Squibb's nivolumab is the most advanced PD-1 inhibitor in development. It has been the talk of the town since presenting phase 1 data at the ASCO conference this summer. Those data showed a response rate of 53% in patients with late stage melanoma taking Bristol's other benchmark melanoma therapy, Yervoy. Now nivolumab is in phase 3 trials with and without Yervoy, and is also being tested in patients with non-small cell lung cancer and kidney cancer.

Merck is hot on Bristol's heels with its own PD-1 inhibitor, lambrolizumab. The drug showed results similar to nivolumab in treating advanced melanoma, and is in mid and late stage trials for breast cancer, bladder cancer, and lung cancer. After several development failures lately, lambrolizumab is a major focal point of Merck's R&D restructuring plans.

Roche's Genentech is quickly becoming a powerhouse in immunotherapy. It possesses the lead PDL-1 inhibitor, MPDL3280A, also being tested in non-small-cell lung cancer, melanoma, and kidney cancer. Interestingly, the drug seemed to be more effective in smokers, a group that is historically difficult to treat. That suggests a mechanism for smoking-induced cancer, and also suggests that PDL-1 expression is an important biomarker for treatment efficacy. Roche is working on a companion diagnostic to help identify patients that will benefit most from PDL-1 inhibition.

We'll have to wait for larger phase 3 trials to see which drug is most effective, but with Yervoy in hand as an add-on therapy Bristol is most likely to find success in the immunotherapy space.

The cancer vaccine
The other approach -- to train immune cells to specifically attack tumor cells they otherwise would have ignored -- has had a tumultuous history. The most notable cancer vaccine flop, Provenge from Dendreon (NASDAQOTH: DNDNQ  ) , fought prostate cancer by removing white blood cells from the patient, conditioning them with markers for tumor cells, and reimplanting them. The treatment appeared to work, but the $93,000 price tag for a single treatment left Dendreon lacking buyers, and the company is now looking to be acquired.

Celldex (NASDAQ: CLDX  ) has picked up where Dendreon left off with a cancer vaccine that works directly in patients. Celldex's lead candidate, rindopepimut, primes the immune system to attack cells expressing a mutated version of epidermal growth factor that shows up in some cases of the brain cancer glioblastoma. After improving overall survival in a phase 2 trial, rindopepimut is now being investigated in a phase 3 trial. Excitement surrounding Celldex's approach made it one of the best performing health care stocks in 2013.

The bottom line
Because these two approaches target different components of immune function, they have a great potential to work synergistically. The real jackpot for investors in companies with PDL-1 inhibitors in the pipeline is a demonstrable effect in multiple cancer types. That versatility will enable the drug to be paired with countless targeted therapies as an adjunct to boost treatment. For investors in companies with targeted cancer vaccines, look for management teams willing to collaborate on, or even out-license, a drug to be packaged with one of the big PDL-1 players.

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Read/Post Comments (7) | Recommend This Article (20)

Comments from our Foolish Readers

Help us keep this a respectfully Foolish area! This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above. Help us keep it clean and safe. If you believe a comment is abusive or otherwise violates our Fool's Rules, please report it via the Report this Comment Report this Comment icon found on every comment.

  • Report this Comment On January 03, 2014, at 5:57 PM, Brovana wrote:

    No mention of NWBO or IMUC but you mention Celldex? Extremely odd or just a very uniformed author.

  • Report this Comment On January 03, 2014, at 8:22 PM, PharmTeam wrote:

    Thanks for reading, Brovana. IMUC took a hard hit after its glioblastoma drug ICT107 failed to meet it's primary endpoint, and investors were (rightly so) not convinced by management's positive spin. NWBO's science is really cool, but with rindopepimut working in vivo, and a robust supporting pipeline, CLDX is in a much better position for sustainable long term growth - that's why I chose to highlight it here.

  • Report this Comment On January 04, 2014, at 7:29 AM, martime wrote:

    Also no mention of CYTR? R they in the mix or just to early to tell?

  • Report this Comment On January 04, 2014, at 7:48 PM, xyz wrote:

    IN THE 1900'S, it was discovered that most cancers are killed off by the immune system. It was a great discovery by the epidemiologists. One day it will make a great movie. Anyway, it's old news, yet I am glad someone is actually doing something.

    As I recall, it was in S. Carolina. They were doing autopsies on the dead from car accidents. Then someone discovered that there were too many cancers. There were too many cancers in the dead. And that's how the story began.

  • Report this Comment On January 04, 2014, at 9:20 PM, czorbs99 wrote:

    All these cancer bio techs mentioned can't even come close to the future potential of Celldex Therapeutics. With 80% institutional ownership, 300 million in cash, and deep pipeline with multiple late sage products makes Celldex a good solid long term Biotech with multiple shots on goal! Celldex has a solid management team and solely owns all products 100%. They are sitting in a good spot right now with a big upside..... providing no bad news in the near term. At $22 it is a great entry point for 2014 and beyond. Good Luck to all.

  • Report this Comment On January 06, 2014, at 6:09 AM, Richmightyclick wrote:


    great to join motley fool but I wont be here for long as I am a terminal cancer patient who is unable to get the new Immune therapy drugs in the Uk .

    As a recently self-educated amateur I must note a few things.

    By bringing the new immunotherapy drugs that are called "blockaders" to the fore the author is saving lives.

    He misses a couple of key points.

    Most chemo treatment is a nightmare for patients-some prefer death.

    But the new drugs are more like aspirin. One shot in the arm of a single PD-1 blockader every three weeks and up to 52% of patients respond.

    Some loose 80% of tumour burden in 8 weeks.

    Some are cured for life.

    Some are unaffected.

    Just to make clear-they are cured for life and retain some learned immunity after treatment for upto a year into the bargain.

    Because these drugs are so easy on the patient, they can be used together to make it harder for the cancer to survive.

    Added vaccines might help too.

    So different blockaders can crush the cancer which cant escape.

    But my interest is in terminal cancer patients around the world who are being left to die by the medical establishment. These drugs MUST be given to terminal cancer patients immediately.

    It is immoral to do otherwise.

    We need a class action against the medical establishment on behalf of the bereaved families who have tested these drugs for years and expect another 3 years to go before they are "safe".

    What a load of hogwash. For terminal patients they are the only safe way out of cancer.

    Something aweful is happening. Something has gone wrong with the drug approval and testing system.

    Terminal patients of many different types of cancer are dying unnecessarily everyday.

    The doctors are playing games with Clinical Trials, some of them apparently using a pin to choose their criteria.

    On the stocks and shares front, BM-S is the leader but Roche is definitely catching up as BM-S should have gained approval Breakthrough for Nivolumab by now.

    After all, with that drug alone they can save thousands of terminal patients lives a year in the UK.

    The main team in this breakthrough was Dr. Jedd Wolchok of Sloan-Kettering Hosp. et al working with BM-S.

    Now Roche are in the game. Merck too, but with PD-L-1 blockaders which are part of the combination solution for certain, along with the PD-1 blockaders. Other companies are desperately trying to catch up or face shrinkage of their cancer business.

    I hope to live to see Dr. Jedd Wolchok, Dr. Jim Allison and their team get The Nobel Prize for Medicine.

  • Report this Comment On January 06, 2014, at 7:18 AM, Richmightyclick wrote:

    On a technical note subsequent to my previous comment, cancer drugs that produce large responses with small side effects are almost unheard.

    In the case of PD-1 blockaders (and maybe PD-L-1 blockaders) the effects can be premanent.

    That is, a complete cure for cancer-no cancer cells of this type can survive in the body. You would have to get another form of cancer, or an identical form of cancer to fall ill again and require more treatment.

    These drugs work for many types of cancer better than others. Some terminal melanoma sufferers saw their tumours dissappear and leave only scar tissue-ugly but not cancerous.

    Melanoma cancer was trialed earlier as the tumours are mostly visible on the skin.

    The list of tumours were the best results are found is growing. The commonest NSC Lung Cancer, all Renal cancer, Melanoma, Gastric, and 1 other are in the list so far.

    Other cancers don't react as well by percentages.

    As an example a PD-L-1 blockader is less effective for Renal cancer than NSC Lung cancer.

    A PD-1 blockaders works as well for both.

    It is worth noting for better efficacy that combo treatments are important.

    The cancer can be evasive and use other channels to avoid immune detection. These channels must be block too.

    The problem is that as more immune blockaders are created, the number of possible trial combinations with different cancer vacines increases to hundreds.

    The Clinical Trials system will take decades to work through this as designed.

    Therefore the blockaders must be expressed through to Terminal patients and used in combo of in fast sequence to give a chance of cure and life extension.

    Many types of cancers and patients will not respond well, but they should try...

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Seth Robey

Lab scientist by day. Motley Fool Contributor by night. Fusing a love for science and money into new biotech investment ideas. Follow @SethRobey on twitter.

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