Looking Backward – And a Peek in the Other Direction

Doc Gumshoe looks at the state of cancer treatment... and some of the interesting drug approvals from 2018

By Michael Jorrin, "Doc Gumshoe", January 31, 2019

Chances are not many of us observed New Year’s Eve with celebratory toasts to the glorious year gone by.   Rather, we bid goodbye to 2018 and hoped 2019 would be a better year – for ourselves, our near and dear, our country, and our planet.   However, as I wade through the volumes of healthcare-related stuff that land in my in-box every day, I do find news that is unquestionably positive.  

Let’s lead off with this item:

The cancer death rate in the US has been declining steadily for 25 years

Cancer continues to be the second most frequent cause of death in the US, after heart disease, but the death rate is dropping.   The death rate from cancer rose to a high of 215.1 deaths per 100,000 population in 1991. But by 2016, 25 years later, it had dropped to 156 per 100,000 population, a decline of a bit over 27%.   This decline, starting in 1992, has continued at a steady pace and is expected to continue as time goes on. 2016, by the way, is the most recent year from which the data have been collected and analyzed.   The data were compiled by the American Cancer Society from several registries and published in an article in CA: A Cancer Journal for Clinicians on January 8, 2019. (Siegel R. 2019;69;7-24).

If cancer death rates had remained at their 1991 peak, this would have resulted in about 2,629,200 more deaths during those 25 years – more than 100,000 per year.   Over a ten year period from 2007 to 2016 the decline in the death rate was somewhat different in men and in women. In women the cancer death rate declined by approximately 1.4% per year, while in men it dropped by 1.8% per year.

The decline in the cancer death rate was in sharp contrast to what we had seen through most of the 20th century, when cancer death rates were rising, seemingly inexorably, every year.   This increase was primarily driven by the increase in smoking and tobacco use, which affected both sexes and persons of all ages, and caused major increases in lung cancer incidence.   And it is the reversal of that smoking trend that has mostly brought about the decrease in cancer deaths, although improved medical treatment for cancer has certainly played a major part.

The highest death rates in both men and women are due to cancers of the lung and bronchus, which account for 24% of the cancer deaths in men and 23% in women.   However, in terms of incidence, these are not the most frequent cancers. In men, the most frequent cancer is cancer of the prostate, accounting for about 20% of all cancers.   And in women, the most frequent cancer is breast cancer, which accounts for about 30% of cancer incidence. But both of these cancers have a relatively high survival rate. The 174,600 cases of prostate cancer estimated to occur this year are expected to cause 31,620 deaths, for a survival rate of a bit over 80%.   In women, the 268,600 predicted cases of breast cancer are expected to lead to 41,760 deaths, for a survival rate of about 84%.

This contrasts sharply with cancers like pancreatic cancer, the incidence of which in men is 29,940 cases with a predicted death rate of 23,800 – a survival rate of about 20%.   And in women, the 26,830 cases of pancreatic cancer are predicted to lead to 21,950 deaths, for a survival rate of 18%.

The survival rates for lung and bronchial cancers are not as bad as that, but by no means are they rosy.   In men, 116,440 cases of lung cancer are expected to cause 76,650 deaths, for a survival rate of about 33%, and in women the predicted incidence and mortality rates are 111,710 and 66,010, meaning that the expected survival rate will be about 40%.

All told, the survival rates for women are somewhat higher than for men.   The total predicted new cases annually of cancer in men is 870,970, and the predicted cancer deaths total 321,970, for a survival rate of about 63%.   In women, those figures are 891,480 and 285,210, suggesting a survival rate of about 68%.

Those numbers for incidence and survival are predicted based on current statistics.   The survival rate percentage calculation is based on the assumption that, for example, a man who has had prostate cancer and dies from any cause other than that specific cancer is a prostate cancer survivor; similarly for all the other cancers mentioned.    That assumption is likely flawed to some degree. A person who has lived with lung cancer for several years and dies due to a heart attack should perhaps not be counted as a lung cancer survivor. But the numbers certainly provide a good picture of expectations: for example, a woman is likely to survive breast cancer, but not pancreatic cancer.

Another way of looking at the probability of surviving cancer is to consider the five-year survival statistics.   These are more easily and more precisely measured – we don’t have to wait until the patient dies to decide whether he/she survived a particular form of cancer.   We only need to check at the five year-mark after the diagnosis. Five-year survival numbers at first glance are a great deal more optimistic than the ultimate survival statistics given above.   For example, for all stages of these cancers combined, the five-year survival rates are highest for prostate cancer (98%), skin melanomas (92%), and breast cancer in women (90%). As expected, these rates are lowest for pancreatic cancer (9%), liver cancer (18%), esophageal cancer (19%), and lung cancer (19%).   

It should be noted that those five-year survival rates should not be taken as cure rates.   A man who has is still alive five years after a diagnosis of prostate cancer has not necessarily been cured.   Perhaps the cancer is merely indolent. These rates are partly indicative of the aggressiveness of a particular form of cancer, as well as being partly indicative of the likelihood of effectiveness of treatment for that cancer.   For example, the five-year survival rate for prostate cancer lumps in the men who have opted for definitive treatment, such as prostatectomy, with the men who have opted for “watchful waiting.”

Despite all the caveats mentioned above, the overall picture is positive.   The five-year survival rate for all cancers is about 67%, which is pretty close to the predicted total survival rates of 63% in men and 68% in women.   The Doc Gumshoe take on this is that all in all, we have about a two out of three chance of surviving an attack by the big C.

Unfortunately, those optimistic statistics are not evenly distributed across the entire population of the US.   The five-year survival rates for African-Americans is about 62%, and cancer mortality varied markedly between more affluent and poorer counties in the US.   For example, mortality rates for cervical cancers in the poorest counties were twice as high as in the wealthier counties, and 40% higher for lung and liver cancers.   After adjusting for sex, age, and stage at diagnosis, the relative risk of death after a cancer diagnosis is 33% higher in black than in white patients, and about 50% higher in native American and Alaskans than in white patients.

Several factors contribute to these large disparities.   A factor that probably contributes most to those differences in cancer death rates are the much higher rates of smoking and tobacco use in certain segments of the US population.   For example, about 24% of adults with 12 or fewer years of education, but no high school diploma, are smokers. This compares with the 8% of college graduates who are smokers. Also, about 25% of adults who live below the poverty level are smokers, compared with those who live above the poverty level, 14% of whom are smokers.   Poverty and fewer years of education are more characteristic of African-American and native American/native Alaskan populations than of the white population.

Another factor, likely connected with lower income and lower educational status, is whether individuals benefit from the screening and preventive measures that have been demonstrated to mitigate several kinds of cancer; i.e., mammograms, colonoscopies, PSA tests, chest X-rays, and several others.

Of course, a major factor is health insurance.   Individuals who do not have health insurance of any kind are much less likely to be screened for cancer or to employ the preventive measures mentioned.   For many uninsured persons, the health-care facilities that they use are frequently emergency departments, and cancer is a disease neither best treated nor screened for in the emergency department.

And a factor that may have more to do with geographical location is access to health-care facilities.   Individuals who have difficulty reaching the location of an appropriate health-care facility are much less likely to start a course of treatment that could, if initiated promptly, lead to remission or at least slow the progress of a cancer.   

What accounts for that decline?

The single biggest factor is a substantial decline in smoking.   Cigarette smoking among adults in the US has shrunk from 20.9% in 2005 to 15.5% in 2016.   The proportion of smokers who have quit the habit has grown from 50.8% in 2005 to 59% in 2016, and among smokers the average number of cigarettes smoked daily has also declined.

The Centers for Disease Control reports disparities in smoking that track pretty closely with the disparities in cancer death rates in the US.   I quote:

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“Despite this progress, disparities in smoking persist across population groups.   Cigarette smoking was especially high among males, those aged 25-64 years, people who had less education, American Indians/Alaska Natives, Americans of multiple races, those who had serious psychological distress, those who were uninsured or insured through Medicaid, those living below the poverty level, those who had a disability, those who were lesbian, gay, or bisexual, and those who lived in the Midwest or South.”

Some of the decline in cancer deaths is certainly due to the gradual improvements in cancer treatment that have been achieved in the past 25 years.   Doc Gumshoe discussed in considerable detail the current state of cancer treatment as well as future prospects in a pair of disquisitions in the fall of 2018, coming to the conclusion that the progress in cancer treatment has been real.   The most advanced and still somewhat experimental therapies, such as those based on gene editing, have not yet resulted in statistical changes in the cancer death rate. But the improvements in the fundamentals of cancer treatment have been real and meaningful.   Advancements in imaging have improved outcomes in surgery and radiation therapy for cancer. You could say that these advances have made it possible for the clinicians to really see what they’re doing. And what used to be lumped under the somewhat despective category of chemotherapy has also advanced in ways that have transformed chemo from “poison” to carefully targeted therapy, taking aim at cancer cell replication and at the mechanisms that the cancer cell uses to extend its life beyond that of normal human cells.   It would be difficult to attribute specific statistical results to these advances in treatment, but their overall effect on survival is surely significant.

2018 was a record year for new drug approvals by the FDA

By the FDA’s reckoning, they put 59 new molecular entities (NMEs) across the finish line in 2018, which topped their previous record of 53 NMEs in 1996.   (“New molecular entities” is the approved jargon for new drugs, perhaps in an effort to fudge the point that some of these NMEs may not turn out to fully qualify as drugs in that their clinical benefit may turn out to be minimal.   But Doc Gumshoe will call them “drugs” all the same.)

The cancer category was the one with the most newly-approved drugs, 16 in 2018 alone.   The number itself is surprising; for example, in 2016, the total number of newly approved drugs was just 22.    That cancer drugs should top the list should come as no surprise, since cancer – in spite of the decline in cancer mortality discussed above – continues to be a major killer, and even in the cases where the patient evades the Grim Reaper, it is difficult and complicated to treat.   And add to that the troublesome facts that there are many, many different forms of cancer, and no single form of treatment is effective across the range of cancers.

From the standpoint of drug development, the approach taken is usually to take aim at a specific form of cancer.   More drugs were approved for cancers of the blood than for solid tumors, and some of the drugs were approved for third-line treatment of cancers such as hairy-cell leukemia and chronic lymphocytic leukemia (CLL).   You may ask (forgive me for putting words in your mouths!) why do we need third line drugs if there are already approved first- and second-line drugs?   Well, you already know the answer: it’s for the treatment of patients who have failed to respond to the first- and second-line drugs.   And in cancer particularly there are many such patients.

But another reason, which Doc Gumshoe has pointed to in numerous rants, is that the pharma companies, in looking for ways to get their candidates past the FDA, need to demonstrate some success in clinical trials, and they don’t want to go head-to-head with the established first-line drugs in diseases like CLL, or, indeed, in any disease.      

The hope of the pharma outfits is that their newly-approved drugs will edge their way past the third-line designation into more general use.   Once a drug is approved by the FDA, physicians can use it for whatever they please, and if these new third-line drugs perform as well or perhaps even better than their supposed betters – and particularly if they are better tolerated – they may well be widely adopted, not only as the initial treatment, but also for cancer forms similar to, but not precisely identical with, the cancers for which they were initially approved.   Third-line approval for a rare cancer is a way into the game.

Several drugs were also approved for rare non-cancerous diseases, although not as many as in the cancer category.   We’ll identify the drugs and the diseases a bit further down when we go through a partial list of 2018’s new drugs.   But the particular factor that merits our attention is that the FDA has been applying somewhat more relaxed standards to drugs that treat patients with rare diseases, for several reasons.   One is that in many such diseases, the new candidate drug may be the only available option for those patients. If this new drug offers patients with a rare disease some legitimate hope for treatment, it should not be made to meet the same requirements as yet another antihypertensive or cholesterol-lowering agent.   Patients with those conditions have an abundance of options, while the patient with a rare disease may have none.

Much the same is true for patients who have failed to respond to first- and second-line cancer drugs.   They may be said to be “out of options.” But a new drug may indeed offer these patients an option, and there is a sound rationale for applying a more lenient standard to these candidates.

Here’s a partial list of drugs approved in 2018:

Biktarvy (bictegravir, from Gilead, for HIV).   The new molecular entity, bictegravir, is combined with Gilead’s previous combination of emtricitabine and tenofovir, marketed as Descovy.   Bictegravir is an integrase inhibitor, which prevents the viral genome from being inserted into the DNA of host cells, that being the way HIV and perhaps other retroviruses replicate.   The peak sales estimates run from $6 billion to as much as $10 billion.

Trogarzo (ibalizumab-uiyk, from TaiMed Biologics, for multidrug-resistant HIV).   The mechanism of action of this drug is totally new. It binds to an extracellular domain of the CD4+ receptor, blocking the avenue through which the virus enters host cells.   TaiMed has licensed a Canadian company, Theratechnologies, to market Trogarzo in North American. In the US, an estimated 20,000 to 25,000 patients have developed resistance to HIV treatment options, and Trogarzo is thought to have a good shot at $1 billion in sales.

Tavalisse (fostamatinib, from Rigel Pharmaceuticals, for chronic immune thrombocytopenia).   This agent, a tyrosine kinase inhibitor, targets the underlying cause of thrombocytopenia by preventing destruction of platelets (thrombocytes) by tyrosine kinase.   The function of platelets is to stop bleeding by forming blood clots wherever the bleeding occurs. In immune thrombocytopenia, the immune system attacks platelets, so patients with this quite rare disease tend to suffer from bruising and, more seriously, internal bleeding, as well as fatigue.   The disease affects perhaps 150,000 persons in the US, so Tavalisse is not likely to make Rigel a mint; the peak sales estimate is $300 million. Rigel had previously tried fostamatinib as an agent for rheumatoid arthritis with no success, so the thrombocytopenia indication is a big boost.

Aimovig (erenumab-aooe, from Amgen/Novartis, for migraine).   Aimovig is the first drug in a new class of migraine drugs called CGRP inhibitors, which Doc Gumshoe wrote about in some detail back in August of 2018.   Here’s a bit of what I said:

”Aimovig’s mechanism is the inhibition of a molecule involved in triggering migraine attacks, calcitonin gene-related peptide (CGRP). Aimovig may be a valuable drug not only for persons with chronic migraine episodes, but for those with episodic migraines – a much larger patient population that has migraine episodes much less frequently than the chronic migraineurs.   Aimovig was compared with placebo in three clinical trials in this population, and the results were that treatment with Aimovig resulted in between 1 and 2½ fewer monthly migraine days. Aimovig is given by means of self-injections every month, which is a considerable advantage over the 30 monthly subcutaneous injections required for every Botox treatment. As with Botox treatment, patients using Aimovig to reduce the frequency of their migraines can also use drugs such as triptans to reduce the severity of a single migraine episode.   The most common side effects reported by patients in the Aimovig trials were injection site reactions and mild constipation.”   

Migraine is a common affliction both in the US and on Planet Earth.   Estimates are that about 18% of women, 6% of men, and 10% of children experience migraines from time to time – a total of about 39 million migraineurs.   That’s a big market for a drug with a list price of about $6,900 per year. Peak sales estimates are about $1.2 billion. But CVS Caremark has just given preference to a couple of competing CGRP agents, Emgality from Eli Lilly, and Ajovy from Teva, both of which are discussed below.

Doptelet (avatrombopag, from Dova Pharmaceuticals, for thrombocytopenia in persons with liver disease).   What this agent is meant to do is increase platelet count in persons with liver disease prior to surgery, so that patients will not have to undergo potentially dangerous – and expensive! – blood transfusions.   This is Dova’s first commercial product, and analysts are somewhat skeptical about its chances for success in the marketplace. Five-day courses of the 40 mg dose will cost $9,000, and $13,500 for the 60 mg dose.   Analysts suggest peak sales of perhaps $650 million.

Epidiolex (cannabidiol, from GW Pharma, for Lennox-Gastault and Dravet syndromes).   Epidiolex is the first cannabis-based prescription drug to be approved in the US, and although the drug got the FDA nod of approval in June of 2018, the drug could not be launched in the market until the Drug Enforcement Administration rescheduled Epidiolex as a Schedule III drug, while leaving cannabis and cannabidiol as Schedule I substances, meaning that they have no accepted therapeutic value and high potential for abuse.   According to the evidence presented to the FDA, Epidiolex does not interact with cannabinoids receptors. The precise mechanism through which it wards off the seizures produced by those two syndromes is unclear. Both Lennox-Gastault and Dravet syndromes are types of epilepsy and result in seizures that primarily affect children and young people and are more frequently fatal than other epileptic seizures. Epidiolex does not appear to block the underlying pathology of epilepsy, but is effective in preventing the occurrence of seizures.   Peak sales estimates are in the $1 billion range.

Mektovi/Braftovi (binimetinib/encorafenib, from Array BioPharma, for BRAF-mutated melanoma).   The combination drug targets two mechanisms that together are active in the proliferation of melanoma – Mektovi employs MEK, which inhibits the MAPK signaling pathway for tumor cell growth, and Braftovi inhibits the proliferation of cancer cells with mutated BRAF genes.   In a pivotal trial of melanomas that cannot be surgically removed or that have metastasized, the Mektovi/Braftovi combination nearly doubled survival compared with Zelboraf, a Roche drug that had previously been the drug of last resort in these patients.   Although the patient population for which this drug is appropriate is not large, they tend to be treated by a relatively small number of prescribers, so Array is optimistic about being able to market their drug effectively. A sales estimate is not available.

Tibsovo (ivosidenib, from Agios Pharmaceuticals, for relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation).   Agios recently partnered with Celgene to launch Idhifa, which treats AML patients with the IDH2 mutation, so between those two drugs, about AML patients with those two IDH mutations – about 20% – will be covered.   Potential threats to the market success of Tibsovo are the CAR-T therapies that several big pharma outfits are developing, but the CAR-Ts will surely be considerably more expensive. Peak sales estimates for Tibsovo run around $300 million.   

Onpattro (patirisan, from Alnylam, for polyneuropathy).   Onpattro is a small interfering ribonucleic acid (RNA) which inhibits the gene that causes hereditary transthyretin-mediated polyneuropathy.   Onpattro encases the RNA into a lipid nanoparticle to deliver the drug directly to the liver, to stop the production of disease-causing proteins.   The drug needs to be given intravenously once every three weeks, and is priced at $345,000 per year after discounts. It has been put in the shade by another similar drug, Tegsedi (of which more later), which was approved a couple of months after Onpattro.   But the main difference is that Tegsedi comes in a prefilled syringe, and patients can administer it themselves. Nonetheless, analysts project a peak sales estimate for Onpattro of about $1 billion.

Lumoxiti (moxetumomab pasudotox-tdfk, from AstraZeneca, for hairy cell leukemia).   Lumoxiti is for patients with this form of leukemia who have undergone at least two previous therapies.   This is by no means a small patients group – about 30% to 40% of patients treated initially with purine analogs relapse within ten years after their first treatment.   The peak sales estimate for Lumoxiti is about $500 million.

Ajovy (fremanezumab, from Teva Pharmaceutical, for migraine).   Like Amgen’s Aimovig, Ajovy is a CGRP inhibitor (see under Aimovig, above).   Ajovy has an edge over Aimovig in that it has been given preference by CVS Caremark.   It is given by subcutaneous injection, either a 225 mg dose given monthly or a 675 mg dose every three months.   Peak sales estimates for Ajovy are $500 million.

Copiktra (duvelisib, from Verastem Oncology, for third-line treatment of chronic lymphocytic leukemia (CLL), small lymphocytic leukemia, and follicular lymphoma).    Copiktra inhibits P13Kδ and P13Kγ. These are kinases, part of a group of enzymes that act on cell growth. The kinases inhibited by Copitkra stimulate the growth of specific blood cancer cells.   Copitkra will need to compete with other P13K inhibitors such as Gilead’s Zydelig, which was on track to bring in $150 million in 2018. Copitkra’s monthly list price has been set at $11,800, and peak sales estimates run from $500 million to $850 million.

Emgality (galcazenumab, from Eli Lilly, for migraine).   Emgality is the third CGRP inhibitor, after Aimovig and Ajovy, to hit the bull’s eye in 2018.   Of the three CGRP inhibitors, Emgality may well be the winner, particularly because it has also received an FDA “breakthrough” designation to prevent cluster headaches.   Cluster headaches are essentially different from migraines. They are very painful, short in duration, affect a small area of the head, and tend to occur daily over a short period, usually only a week or two.   Emgality, along with Aimovig, has priority coverage by Express Scripts, which will be a significant boost. Peak sales estimates are about $700 million.

Vizimpro (dacomitinib, from Pfizer, for EGFR-mutated non-small cell lung cancer). EGFR is epithelial growth factor receptor.   These are present on the surface of normal as well as well as cancer cells, and, as the name implies, are the receptors for signaling proteins that promote cell growth, whether in normal or in cancer cells.   In patients with mutated EGFR, the signal is in the “on” position all the time, and cancer cells grow quickly. EGFR mutations are present in about 15% of lung cancer patients in the US, although much higher in persons of East Asian descent.   Non-smoking lung cancer patients are more likely than smokers to have that mutation, and female patients more likely to have the mutation than males. Vizimpro interrupts the mutated EGFR signal. Vizimpro’s price tag is $12,400 per month. Peak sales estimates are not available.    

Tegsedi (inotersen, from Akcea Therapeutics, for hereditary transthyretin-mediated amyloidosis).   Amyloidosis is the buildup of a protein called amyloid in the body’s organs and tissues, particularly in the peripheral nervous system, resulting in a loss of sensation in the muscles and sensory cells.   The autonomic nervous system, which controls heart rate and other involuntary body functions, may also be affected. The incidence of transthyretin-mediated amyloidosis is immensely varied, ranging from one in fewer than 1000 individuals in some communities in northern Portugal to perhaps one in 100,000 persons in Americans of European descent.   The disease is progressive and usually fatal. Alnylam’s Onpattro (see above) had previously gained FDA approval for this indication. Akcea set the price tag for Tegsedi at the same figure, $450,000 per year. Peak sales estimates are not available.

Talzenna (talazoparib, from Pfizer, for BRCA-mutated HER2-negative breast cancer).   BRCA1 and BRCA2 are BReast CAncer genes 1 and 2; mutated genes increase the risk of breast cancer.  HER2 is human epidermal growth factor 2, a protein that appears on the surface of some (but not all) breast cancer cells: HER2-negative breast cancer refers to those breast cancers in which HER2 is not a factor.   BRCA mutations are rarely found in HER2 positive breast cancers. That being said, Talzenna is a drug in a class called PARP inhibitors which were chased out of the limelight when gene-editing therapies like CRISPR and CAR-T got all the publicity; however, PARP inhibitors have demonstrated considerable efficacy in treating several cancers.   PARP (poly ADP ribose polymerase) repairs errors in DNA transcription that occur in all cells during cell replication; PARP inhibitors prevent that repair in cancer cells and appear to be effective in other forms of cancer other than breast cancer, including ovarian, pancreatic, and lung cancer. Sales estimates are not currently available, but Pfizer’s ability to market any of their drugs effectively should not be underestimated.

Lorbrena (lorlatinib, from Pfizer, for ALK-positive non-small cell lung cancer). In a mutation, ALK (anaplastic lymphoma kinase) can rearrange its genetic components such that it codes for a type of tyrosine kinase that drives the growth of some lung cancers.   Lorbrena is currently indicated only for previously treated patients, but it may be paired with Pfizer’s Bavencio, and if Pfizer can snare a combination therapy approval for Lorbrena/Bavencio, they might take possession of a valuable corner of the oncology market.   No sales estimate is currently available.

Vitrakvi (larotrectinib, from Bayer/Loxo Oncology, for solid tumors with NTKR gene fusion).   What’s unique about Vitrakvi is that it takes aim at solid tumors anywhere in the body as long as they demonstrate a specific feature, that being the NTKR gene fusion.   NTKR has three subtypes, neurotrophin receptors TRKA, TRKB, and TRKC; these in turn are tropomyosin receptor kinase A, B, and C, which stimulate solid tumor growth. Now that we have sorted out the abbreviations, let us look at the drug itself.   Vitrakvi is a first-generation TKR antagonist, and in patients with those specific cancers it has delivered a response rate of greater than 75%. In some patients, NTKR-positive cancers eventually become resistant to treatment with a TKR antagonist, and second generation treatment options are currently in early clinical trials.   Bayer, having fronted a considerable sum to Loxo, has high expectations for Vitrakvi. Peak sales estimates are $850 million.

Taking a step back to look at this in perspective, what do we see?

A look at the overall picture

If we ever wanted evidence that cancer is not one single disease, but a very large group of diseases that share a common characteristic, we have only to look at recent cancer drug approvals.   The cancer subtypes vary by the sites in our bodies that they invade, and even within those sites, they vary greatly by other characteristics, such that a single treatment approach is not likely to deal with all the subtypes.   Thus we see that even within the subtype of cancers of the blood there are sub-subtypes based on the genetic identities of the cancer cells. For that reason, as research has advanced, treatment for cancers has narrowed and sharpened its aim, targeting the individual characteristics of those cancers and their genetic identities.   This is true not only for cancers, but for other diseases.

The newly- approved drugs make use of many different mechanisms of action to accomplish their goals.   Among the group of drugs reviewed above, we find integrase inhibitors, which prevent viruses from inserting their genome into host cells; blockers of the CD4 extracellular domain, which is an entryway for viruses; tyrosine kinase inhibitors; three drugs that inhibit calcitonin gene-related peptides (CGRP) which are thought to cause migraine; the first cannabis-based drug; a combination drug that inhibits two mutations; a drug that encases RNA in lipid nanoparticles for infusion; a drug that targets all solid tumors with a specific mutation; and several others aimed at specific mutated targets.

What this means, from the perspective of Doc Gumshoe, is that at the same time that the targeting of drug treatment is getting much narrower – and, we hope, more accurate – the scope of the campaign is getting much, much wider.   We no longer are pinning our hopes on one single drug to end cancer. We know that won’t happen. The same thing is true of other diseases and conditions. The approach seems to be to surround the enemy with a vast range of attacking mechanisms, and then go after each one of the enemy’s combatants with the most effective weapon.

And, touch wood, it may be that we’re winning!.

* * * * * * *

I had somehow thought that I would cover a whole lot more territory in this piece, but I underestimated how darned much stuff there was to squeeze into those topics.   So the rest of the news will have to wait until the next blog. Best to all, and keep those comments coming! Michael Jorrin (aka Doc Gumshoe)

[ed note: Michael Jorrin, who we like to call ”Doc Gumshoe,” is a longtime medical writer (not a doctor) who shares his mostly non-investing-related thoughts with the Gumshoe community a couple times a month. You can see all of his columns here.]