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    Good news…


    [FDA Approves Merck’s Cancer Drug

    Pembrolizumab Part of New Wave of Drugs Aimed at Bolstering the Body’s Immune System

    By Peter Loftus

    Updated Sept. 4, 2014 3:01 p.m. ET

    U.S. regulators on Thursday approved a new kind of cancer drug from Merck & Co. that is designed to unleash the body’s immune system against tumors and could generate billions of dollars in sales.

    The drug, which Merck plans to sell under the brand name Keytruda, is part of a long-anticipated wave of medicines that could transform cancer treatment and forge a large new market for pharmaceutical companies.

    The Food and Drug Administration cleared the drug, pembrolizumab, for the treatment of a deadly form of skin cancer, melanoma. The approval followed a swift review of data from a relatively early-stage human trial—an unusual move reflecting the medical community’s keen interest in pembrolizumab.

    The infused drug is a new type of immunotherapy, a category of treatments that harness the immune system to fight cancer. It was approved for people who’ve failed to respond adequately to Yervoy, a Bristol-Myers Squibb Co. immunotherapy that works in a different fashion, and certain other drugs.

    Pembrolizumab is the first so-called PD-1 inhibitor to hit the U.S. market. The drugs block a protein called programmed death receptor 1, or PD-1, which acts as a brake on certain immune-system cells to prevent them from attacking healthy tissue. Cancer cells can escape destruction by latching onto PD-1; PD1 inhibitors block this interaction at the site of the tumor, releasing the immune system brake and allowing it to destroy the cancer. Yervoy also lifts a brake on the immune system but does so earlier in the immune-cell activation process, which researchers say may cause more collateral destruction of normal tissue than with PD-1 blockers.

    Pembrolizumab and other PD-1-targeting drugs—including those developed by Bristol-Myers and Roche Holding AG—have generated excitement among doctors because they appear to induce relatively high rates of tumor shrinkage and prolong average survival beyond historical norms in clinical studies. Researchers say the side effects associated with the drugs appear to be manageable.

    “PD-1 is truly a game-changer. It’s active in a way that other drugs are not,” said Lynn Schuchter, a medical oncologist who heads the melanoma program at the Abramson Cancer Center of the University of Pennsylvania and has assisted in clinical trials of the Merck drug. “And what’s been interesting is the activity of PD-1 beyond melanoma. It looks to be active in bladder and renal and lung cancer. So this is bigger than melanoma.”

    Some analysts believe total annual sales of cancer immunotherapies could reach about $32 billion by 2025, if more drugs make it to market to treat a range of cancers. Leerink Swann estimates Merck’s new drug alone could generate annual sales of more than $6 billion by then.

    A competing PD-1 inhibitor, nivolumab, hit the market in Japan this month, at a price of $143,000 for a year’s worth of treatment for the average Japanese patient. The drug, from Bristol-Myers and Ono Pharmaceutical Co., is expected to be reviewed by U.S. regulators in coming months. Other PD-1 inhibitors are expected to have similarly high price tags, which could fuel more debate about the affordability of new drugs.

    Merck didn’t immediately disclose the price for Keytruda on Thursday.

    Until a few years ago, most patients with advanced melanoma could be expected to live less than a year. Bristol’s Yervoy and other drugs targeting cancer-causing genetic mutations have begun to improve the outlook. Now, Merck’s pembrolizumab and other drugs are expected to provide further advances. About 76,000 Americans are diagnosed with melanoma each year, and about 9,700 die of the disease annually, according to the American Cancer Society.

    This summer, researchers said about 69% of advanced melanoma patients receiving pembrolizumab in a clinical study were still alive after one year of treatment and 62% were alive at 18 months. Overall, about 34% of patients experienced tumor shrinkage of 30% or more. About 12% of patients experienced a significant adverse event, such as fatigue, while 4% discontinued treatment because of an adverse event. The trial didn’t have a comparator arm.

    “Now I have patients coming back in significant numbers who are effectively treated with this agent, and the response is durable,” said Antoni Ribas, a melanoma specialist and professor of medicine at UCLA’s David Geffen School of Medicine, who served as lead investigator of the study.

    Still, the Merck drug and other immunotherapies don’t work in every patient and can’t be considered a broad-based cure. Researchers are exploring biological markers such as the presence of certain proteins on cancer cells that may help doctors select patients most likely to benefit from a particular drug—and those less likely to benefit.

    Merck began testing the drug in humans in 2011 in what is known as a “phase 1” study. Such studies are typically conducted in a small group of patients to test whether a drug is safe. Usually, two additional phases of studies—with larger patient populations—are needed to demonstrate a drug’s efficacy and safety before the FDA will consider approving it, but sometimes the agency approves cancer drugs based on early- to mid-stage trials.

    Dr. Ribas said he began to notice positive results relatively soon after he began overseeing pembrolizumab’s testing in melanoma patients. The phase 1 study also included patients with other tumor types such as lung cancer. Merck made the unusual decision to expand and continue the phase 1 study, which eventually grew to more than 1,100 patients of various tumor types, believed to the biggest phase 1 cancer study ever.

    One study participant, 59-year-old Kathleen Thomas of Redondo Beach, Calif., says she felt like she’d been given a “death sentence” when she was diagnosed with advanced melanoma in April 2011.

    Her disease progressed after treatment with surgeries and drugs including Yervoy. She lost weight and strength, forcing her to use a wheelchair. Within months of joining the pembrolizumab trial in late 2012, Ms. Thomas said she began to feel better, regaining weight and using the wheelchair less often. Subsequent imaging scans have shown that her tumors have either shrunk, disappeared or remained stable, she said.

    Patient interest in the Merck drug and other immunotherapies has given rise to petition drives and social-media campaigns seeking access to the drugs before regulators had approved them for sale. Such demand has fueled legislation in some states that gives terminally ill patients a “right to try” certain experimental drugs without having to go through an FDA program for early access, if a drug’s manufacturer is willing.

    Merck started an early access program for pembrolizumab in March but restricted it to patients whose disease had progressed after treatment with Yervoy and, if applicable, a drug targeting a genetic mutation known as BRAF.

    After starting human testing in 2011, Merck raced to close the gap with rival Bristol-Myers, which introduced Yervoy in 2011 and was ahead on testing its own PD-1 inhibitor, nivolumab.

    Merck got a boost in early 2013 when the FDA deemed pembrolizumab a “breakthrough therapy,” a new designation that made it eligible for a speedier review and extra attention from top FDA officials. Last year, Merck’s new R&D chief, Roger Perlmutter, terminated several other R&D projects and shifted resources to pembrolizumab and other promising programs.

    Merck Chief Executive Kenneth C. Frazier, a company veteran since 1992, called pembrolizumab “one of the most exciting programs I’ve been associated with since I’ve been at Merck.” He likened it to the company’s introduction of anti-HIV medicine Crixivan in 1996, among the early protease inhibitors that helped reduce the risk of death from AIDS.

    Merck said in late July that it expects to have enough supply of pembrolizumab to be ready for a market launch, including meeting potential demand for “off-label” uses of the drug, which would treat a cancer type not included in the initial FDA-approved prescribing label.

    More new immunotherapies could be on the horizon. Bristol-Myers expects to file by Sept. 30 for FDA approval of nivolumab as a melanoma treatment, and by year-end for approval of its use to treat lung cancer.

    Bristol’s drug also has generated positive clinical results, and some analysts believe the company will eventually dominate the immunotherapy market. Researchers said this summer that melanoma patients receiving a combination of Yervoy and nivolumab in a clinical trial had a median overall survival of 40 months, though many experienced significant adverse events such as the bowel disorder colitis.

    Catherine Poole

    thanks Jeff, just got the word from Merck in a phone call. Only wish prior ipi wasn’t going to be an issue! Good news indeed! Here’s the scoop: the drug (call Keytruda) will be available in one week. It is given every 3 weeks with a 30 minute infusion. Cost will be $12,500 per month. EAP centers will close and transition to commercial insurance with a transition team. If unable to pay, there will be assistance through: http://www.merckaccessprogram/keytruda.com in 24 hours this site should be up. Yes prior Braf and IPi required but doctors will act accordingly on this as the majority disagree and feel it should be first line therapy.


    Prior ipi and prior BRAF, if BRAF-positive… I’d heard rumors that although prior BRAF was part of the EAP that it wouldn’t be included as part of the FDA approval, that’s too bad.

    Also, the details of Merck’s press release also say not only prior ipi, but disease progression on ipi within 24 weeks (6 months) following treatment and at least two doses of ipi. I wonder what that means for someone who has to discontinue ipi after a single dose, or someone who has stable disease following ipi and then progresses after the six month period? For the latter, do they have to go through ipi retreatment?

    http://www.mercknewsroom.com/news-release/oncology-newsroom/merck-receives-accelerated-approval-keytruda-pembrolizumab-first-fda-” class=”bbcode_url”>http://www.mercknewsroom.com/news-release/oncology-newsroom/merck-receives-accelerated-approval-keytruda-pembrolizumab-first-fda-



    This is just fantastic news!

    I agree (!), it needs to be a first line therapy. I bet the prior IPI and Braf garbage will quickly give way.

    Thanks for being so on top of everything Catherine.



    Such good news to start our Fridays. Having been able to suffer thru only two IPI infusions and currently 3 months into Braf/Mek, I now know what treatment will be next in line. Thx, Merck.


    What a waste of medical resources. I am braf negative so hopefully I won’t have to waste my time, health and money on ipi which, in patients like myself, has only a 6.7% success rate as well as a larger number of toxic side effects than the PD-1 drugs. I am a more than a little put off by the price tags. Perhaps when nivolumab is approved, providing competition the prices will be more reasonable. It is wonderful news for a lot of people. I just hope that we have not added to the environment where you have to be wealthy or have really good insurance to get these medications.

    Catherine Poole

    Work with your doctor on the IPI requirement. I agree the prices are high, $120K for the course of IPI and $12K for a month of PD1. Insurance should cover and I listed a website to help others without resources. The reason they are requiring prior ipi and BRAf is because of the approval is granted for those who have run out of options and based on the trials. Seems all too antiquated for me.

    Also, the cost will be based on your weight for the approved PD1. It is 50mg based and then rises with weight of patient.

    Catherine Poole

    Here’s what I found out about the lawsuit: Right now it is thought that BMS/Ono have only a slight chance of derailing Merck’s progress with Keytruda.

    BMS is not likely to ask for a preliminary injunction to stop the sale of Keytruda. Also, BMS is asking for a jury trial, and that is unlikely to occur for at least another year. At that point, that BMS/Ono have only small odds of winning their suit.

    I hate litigation personally, just eats up a ton of money that could be spend on new discoveries.


    Catherine Poole wrote:

    Also, the cost will be based on your weight for the approved PD1. It is 50mg based and then rises with weight of patient.


    Are you sure about this part? The approved dosage is 2mg/kg every three weeks, so 50mg would only be enough to treat a 25kg person, or 55 pounds, implying that a 110 pound person would be twice the cost, a 165 pound person triple, and a 220 pound person quadruple. From their prescribing information document, yes, it is shipped in vials that contain 50mg each.

    I’m questioning this in part based on what I know about Yervoy/ipilimumab. The dosage is weight based, 3mg/kg, but pricing is not variable based on weight, and it is shipped in two different sizes, 50mg and 200mg vials.

    Just looking to clarify for everyone.




    For IPI, my hospital billed based on the number of vials (in other words by weight). That came to $320K billed (unsuccessfully) to my insurance company for 4 infusions. The insurance company ended up paying out well less than the “list” $120K price that I thought was the standard IPI price. For whatever that is worth — very confusing to me at the time (and I guess still is.)


    Very interesting. I did ipi, too, but don’t recall what went on between the hospital and my insurance company, I’ll have to dig out the paperwork and take a look. If that’s the case with pembro, it seems ridiculous that they “advertise” (not really, but they certainly don’t do a good job of keeping it a secret) a price that would be for a 55 pound person. Granted, the agreed upon rate is what gets paid by insurance and for the uninsured, they claim to have assistance programs available, so in the end, maybe no one actually pays the “weight-inflated” cost?


    Does anyone know how international patients are handled if the patient cannot travel to the U.S. to get the treatment? Thanks in advance!



    Not sure, but I enquired about nivo/ipi before and going to the US is extremely expensive: 160k for the medicines, plus additional costs for hospital care (blood work, day rate for stay, possible on-costs when side effects occur) and travel (in case of nivo/ipi I believe weekly at first).

    However, pembro is also available at more and more locations in Europe, now as EAP and soon hopefully wider when approved by the EU equivalent of the FDA. Where are you located?


    Hi, Rick,

    Thanks a lot for your reply. We are in China where most trials are not available. I contacted Idis and they need to talk with the physician who is registered with them to share the information on global locations? Do you have any idea? Thanks!



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