Keytruda is the biggest drug on the planet in terms of sales, and it's an immunotherapy drug that targets all sorts of cancers. Scientists call it a checkpoint inhibitor and it fights cancer by stopping the cancer cells from hitting the self-destruct button located on all T-cells. T-cells are important because our immune system trains them to kill cancer cells. In essence, they are the body’s standing army that is trained to wage war with cancer cells and a smaller army means less likelihood of success. Keytruda is incredibly popular because it helps people raise bigger T-Cell armies to fight off cancer; however, Merck is hiding a dirty little secret because more of something doesn't necessarily always mean it's better.
Before we blast big pharma giant Merck, let's look at some of the positives. Many don’t realize that Keytruda often cures people where their cancer goes away and never comes back. The complete response rate for Keytruda treating melanoma was 6% at the 2-year point which means the cancer was completely gone for 6% of those that used Keytruda. So Keytruda essentially cures cancer in 6% of melanoma patients, but what about the other 94%? Why aren’t they cured? The reality is that more people eventually overcome cancer but it takes more than 2 years. In Melanoma the 10-year survival rate is an impressive 34% for Keytruda patients but that still means 66% of the people died. For comparison, the 5-year survival rate for lung cancer is 23.2% if you get Keytruda immediately.
Perfect Drug = Not Good Enough to Cure
Merck has the perfect big pharma drug because it works just good enough to keep you alive for a long time provided you keep using it, but not well enough to cure you fast and reduce this monster revenue stream. Let's face it—in 2023, Keytruda was the top-selling drug with $25 billion in annual sales so they have 25 billion reasons to not care about finding a better solution.
The question for Merck isn’t if there is a better solution, but rather why they continue to give Keytruda to people that they know the treatment is going to fail. Since 2019, there has been a medical journal article that is literally the smoking gun capable of taking down Merck’s $25 billion dollar/year empire in cancer treatment, and they are getting a free pass because big pharma refuses to look at any research that would cannibalize existing sales.
To get Keytruda, treatment patients must first test for the presence of a receptor called PD-L1. The idea behind Keytruda is that they are a PD-1 inhibitor so the drug would be worthless if the person didn’t have enough of the PD-L1 receptor being expressed on their T cells. What the study brought to light is that there was an additional biomarker that was extremely accurate in predicting whether or not Keytruda was going to work. The results showed that 100% of lung cancer patients responded to Keytruda if they had low or no Galectin-3 expression on their tumor. Those with high Galectin-3 failed Keytruda treatment 90% of the time.
To give some perspective, Keytruda works 24% of the time to reduce the risk of lung cancer coming back or death. Another way of saying this word sandwich is that people have a 76% chance of dying if they take Keytruda. They don’t tell you that at the doctor's office. What if we could turn that 76% chance of dying if you take Keytruda down to a 0% chance of dying if you take Keytruda? That would be great but it would cost Merck 10’s of billions in revenue and that's the dirty little secret that has been buried in this peer-reviewed journal article.
Merck still doesn’t screen patients by their galectin-3 expression 5 years after this research was published and there has been no follow-up research, but that shouldn’t come as any surprise.
Making Keytruda Better
One person on a quest to develop a better solution is Nobel Laureate Carolyn Bertozzi. In her talk, Sweet Revenge on Cancer, she explains why most people don’t respond to checkpoint inhibitors like Keytruda because other pathways still suppress the immune system.
“While the immune therapies are exciting and new and promising, and life-saving for some people, for most people, they don't work. And the big question in the field is why not? Why don’t they work for everybody and could there be other pathways cancers are using to inhibit immune cells that have nothing to do with PD-1 and CTLA-4. … If you could find other pathways that cancer cells are using to suppress immune cells and inhibit them, maybe there are new drugs you can make to treat more patients or maybe combine those drugs with the first generation of checkpoint inhibitors to cover all the possible pathways. That has been the focus of the field for the last 10 years. What are the other pathways of immune suppression that are playing an important role in cancer?” - Nobel Laureate Carolyn Bertozzi
She makes it sound so simple and obvious but Merck with their billions of dollars is using their research dollars to expand into more types of cancer instead of finding out why their drug doesn't work in a majority of people. They aren’t asking what the other pathways are. The only thing they are searching for is more dollars in other indications.
Additional Promising Checkpoints
Palleon Pharma is working on a drug to treat breast cancer using a novel new pathway related to Carolyn Bertozzi’s field of research. She asked rhetorically what are the other pathways that suppress the immune system but it wasn’t rhetorical at all. She understood that sugars linked to proteins shroud cancer cells and cloak them from the immune system. Cancer hides from the immune system this way. Palleon’s research revolved around “siglecs” (Sialic acid-binding immunoglobulin-type lectins) that are found on all types of immune cells and get triggered to the off position when they come in contact with a cancer tumor's sugar shroud. Preclinical results revealed their idea of cutting sialic acid in a targeted way had a huge impact on breast cancer metastasis mouse models. Combination therapy showed they cured cancer in mice and that future attempts to infect the mice with cancer after they were cured were unsuccessful. They are currently in a phase 2 study with this drug.
The Universal Target in Cancer - Galectins
The mouse studies and clinical trials at Palleon are obviously inspiring, but the following images from combination trials with Keytruda and a galectin-3 blocker are likely to get you fired up and ask why these drugs aren’t on the market yet. The simple answer is greed.
Keytruda in combination with a galectin-3 blocker called Belapectin, which is manufactured and developed by a small biotech called Galectin Therapeutics (NASDAQ: GALT), achieved a 100% response rate at optimal dosing after a small 90-day metastatic melanoma trial in comparison to a 2-year trial with Keytruda alone which clocked in with a 33% response rate for treating metastatic melanoma. There’s more, Galecto Biotech (NASDAQ: GLTO) did a study and had a 40% response rate in its first cohort of patients and then got a 60% response rate in the second cohort of patients on the dose escalation and they stopped without hitting any dose-limiting toxicity.
If the reader can now take a breath and pause for a moment so that they have a clear mind to do the higher level math needed in this comparison—is a 100% responders rate at 90 days a better treatment than 33% responders at 2 years? Is a 60% response rate at 6 months better than 38% in 2 years? If you answered yes to both then you realize that this is some of the best cancer data in the world for the past 5 years and no one is talking about it.
It's still a mystery why both of these companies prioritized developing their liver drugs over cancer treatment because both of these drugs had a statistically significant response rate and would be excellent candidates for approval. Typically a combination therapy drug development program would include collaborations between big pharma and the company developing the additional treatment, but that requires possibly upsetting the Keytruda gravy train.
Galectins Involved in Metastatic Cancer
Statistics show that the primary tumor doesn't kill the cancer patient but eventually, the metastasis will. A mountain of research indicates that galectins are involved in almost every phase of cancer metastasis, making them a universal target in metastasis cancer treatment. Despite the overwhelming evidence, only one company seems intent on pursuing this line of research of creating a metastatic cancer drug. A biotech called Bioxytran (OTCMKTS: BIXT) has made some bold statements that they plan on leading the charge. This short highlight reel is very informative and encapsulates their plan in the span of 3 minutes. What is so intriguing about their plan is that they intend on getting their cancer drug approved as a COVID drug first. While that might sound crazy, viruses impair the immune system in a similar manner as cancer. The method of restoring immune function via a galectin blocker applies to both viruses and cancer.
Before writing this off as snake oil because it treats everything, realize that Bioxytran’s oral galectin blocker had not only one peer reviewed COVID clinical trial with 100% responders rate, but 2 in total. They also had a peer reviewed article published that proved their drug was a highly-targeted galectin-3 agonist which means their drug could be useful in a variety of indications. The company has a cutting-edge platform technology capable of treating many viral and inflammatory conditions. All these galectin blocker companies are perfect targets for big pharma but they have yet to take the galectin blockers’ results seriously.
It's worth noting that Galectin Therapeutics has an interim readout due in December 2024 for treatment of a liver disease called MASH. Positive results are anticipated and could be a catalyst for big pharma to chase down these galectin antagonists because it won’t be long before people ask: “what else do these galectin antagonists work on?” Many may not realize it but MASH is the largest, most lucrative unmet medical need and will surely garner headline status if the results are positive.
Hear No Evil See No Evil, Speak No Evil Pharma
Is the combined wisdom of a big pharma lower than that of a Nobel Laureate who has known for years that Keytruda could be improved, or does pharma know and still choose to do nothing? Whatever the case, it’s clear that big pharmas like Merck are happy to supply Keytruda to continue to expand the number of indications of cancer that it can be used to boost their top line, but they aren’t too interested in putting their own money on the line or getting their hands dirty in running these combination trials that could cannibalize sales.
Progress is “welcomed” only to the point at which it threatens the money train. Clinical trial results with galectin blockers show that patient health comes before money with these combination therapies. They are incredibly effective and look like they are going to reduce the duration of cancer treatment. This is a clear and present danger to the money train which is one possibility why they have steered clear of its development pathway and simply ignored the technology for years. Steering clear of this field of science gives big pharma plenty of plausible deniability that they weren’t looking after patients' best interests; however, that mindset could turn on a dime if any galectin blocker looks like it's going to get approved.
The data is clear, galectin-3 biopsies have a near predictive value of 100% on whether or not Keytruda is going to work. However, the FDA hasn’t pushed to require this test before taking Keytruda and they share in some of the culpability. If there are any cancer patients reading this, realize the FDA is asleep at the wheel because their job is to make sure the drug companies do no harm, and giving Keytruda to people who won't respond opens cancer patients up to the unwanted side effects and expenses of Keytruda. We can point fingers at both big pharma and the FDA, but in the meantime, cancer patients suffer from suboptimal therapy.
Big Pharma’s Next Move
The answer to what's next is: surprise, surprise - more big pharma greed. If Galectin Therapeutics galectin antagonist announces in late December data that's good enough for approval in MASH, the genie will be out of the bottle. This is the biggest underserved indication in biotech and it will get press. Once the news is out, big pharma can no longer ignore the galectin science and will need to secure a galectin antagonist. Merck for one cannot sit on the sidelines while some other drug company figures out that they can charge more for the galectin antagonist than Keytruda. Quite frankly, galectin blockers are more important because they have the potential to stop metastasis, the thing that ultimately kills cancer patients. So maybe greed is good after all.
