Why Inclusion in Global Oncology Clinical Trials is critical for Canada

There has been much talk lately about Canada not attracting sufficient clinical trials in oncology. This is a problem. A big problem.

Clinical trials, are literally the lifeline to new treatments. They are usually designed for those who have exhausted all funded and known treatments and now must try something experimental with the hope of extending survival. For physicians, this is a way of not only offering an additional line of therapy to patients who need it, but a way to familiarize themselves with a drug, that may become part of their arsenal in the future. Also, clinical trials cover all the associated treatment costs, which is a nice financial reprieve for hospitals.

There are many reasons why we are not attracting clinical trials. In my point of view, these are 2 of the many key issues.

First, we have lost our status in the world markets. Canada is not a lucrative market.  In fact, it can be detrimental to lucrative markets, as countries now choose to launch here after the US and EU due to reference pricing. There is so much pressure on pricing in Canada, that some companies do not even launch here.

Secondly, the fact that we do not run molecular biomarker tests such as Next Generation Sequencing (NGS) on all patients, is also an issue. NGS, or other screening tools, not only offers a precision oncology approach to patient care, but arms hospital with data that can attract in-bound clinical trials. How can you attract a trial for a certain genomic profile, if you don’t even know what % this profile represents of a cohort of cancer patients? You need retrospective data, as no company is going to keep its fingers crossed in the hope that you accrue enough patients.

These gaps, in addition to others, are hindering our ability to attract clinical trials. More importantly, patients are losing out on the chance to access cutting edge therapies. It’s a lose/lose situation.

Two drops of Justice: The Theranos Story

Is hindsight 20/20? Maybe, but not in this case. All that was needed was a good lens cleaner to see what was so clear to many. Read on and you will see why.

Theranos CEO Elizabeth Holmes was convicted on 4 charges and sentenced to 11.25 years in prison, while COO Sunny Balwani, was convicted on all charges and sentenced to 14 years.

When one looks back, two things are hiding from the public in plain sight.

First notice all the investors who were swindled by these two in their disgraced blood testing startup, none were the typical Venture capital or private equity firms that invest in cutting edge medical or biotechnology. Notice how many of the investors were statesman, family offices, and wealthy investors outside the medical ecosystem. Moreover, one would assume the likes of Thermo Fischer, Becton Dickinson would take a minority stake in these companies with the hope of acquiring them eventually. Nope, they ran the other way. Why you may ask? This leads me to my second point.

In life sciences, as in most industries, there is a proof of concept. Some genius in a lab discovers a mutation, a biomarker, a signal and before you know everyone pounces on it. Look no further than PD-1 and PD-L1s with 93 bispecific antibodies in development targeting PD1/PDL1. Why because it probably works.  In Theranos’ case—nobody, including the big names in the industry with decades of experience, thousands of scientists could run 200 tests on a drop of blood. But these two charlatans could! And the Silicon Valley old adage of “fake it till you make it” might be acceptable for benign software but not when peoples’ blood results hang in the balance.

When drugs get into the wrong hands

Anywhere you look there is someone touting amazing weight loss stories with Wegovy® (semaglutide) and Mounjaro®(tirzepatide). These drugs achieve weight loss by mimicking naturally-occurring hormones called GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide). Both help regulate the release of insulin, and in turn seem to influence feelings of satiety. 

Unfortunately, many of those touting the drug are not diabetic nor obese with a BMI ≥30. Already there is a shortage of supply with diabetics unable to fill their much needed prescriptions. Also, there is word that people are accessing discounts for which they do not qualify. Social media, fed by Hollywood, is paving this road and it will lead to nowhere good.

These drugs are new to the obesity category and do not have years of real-world evidence that can help guide their usage. In fact, once patients cease treatment the weight tends to creep back thus already leading manufacturers to consider trialing a maintenance option. Also, these drugs are not without side effects and need to managed by doctors who are experienced in managing such.

It’s always tricky when a drug has a specific indication that is also attractive to the mainstream. Will people relinquish their prescription to ensure supply for diabetics?

Enter the clever Amgen with its dubbed AMG-133 which for now will only seek an obesity indication knowing quite well that it cannot compete in the diabetes market against the 2 powerhouses of Eli Lily and Novo Nordisk. By focusing thus far on obesity, Amgen avoids the diabetes vs obesity moral supply issue.

I am curious to see what happens here. Does this category succeed or implode on itself as other obesity drugs have? Does the FDA step in and regulate its use both at the patient and treater level? Buckle up everyone, it should be an interesting ride…

The Sweet Spot for Corporate War Gaming is Some Moderate Level of Uncertainty

A War Gaming workshop can be powerful tool when used in the right scenarios. When no amount of analysis can provide the right answer, Wargaming can shed valuable light on the range of possibilities that executives should be considering. In fact, the sweet spot for Wargames is some moderate level of uncertainty.

For those not familiar with War gaming, it is a conducted within a company among various departments and teams. Participants are typically divided into group representing various competitors. The role of Wargaming is to play out every possible scenario and establish the best course of action.

What do you get from War gaming?

•      Identify competitive risks and opportunities

•      Refine current strategies and contingency plans

•      Provide a realistic assessment of your plan

•      Better market performance thanks to enriched understanding of competitors

•      An agile, actionable, and outcomes oriented competitive strategy

Having conducted numerous workshops over the years, I will tell you that the sweet spot for War gaming is a moderate level of uncertainty. It can be daunting at first, and at times require a crystal ball, but allows for the teams to come up with numerous strategic contingent plans that mirror possible outcomes.

In fact some of the best War games are the ones that do not divide the teams up by competitors, but rather, by uncertainties. For example, an uncertainty can be government legislation and its impact on a given industry.  In lieu of dividing up participants by competitors, one can divide them up by 4 potential outcomes of legislation and have the teams “battle it out”. In return, the company will have 4 different contingent plans in place should one of the 4 paths need to be taken.

The Fox Guarding the Hen House: Using Arbitrary Metrics

As many of you, I got caught up in the whirlwind of a possible new drug entry for Alzheimer disease. A very underserved area juxtaposed by an aging population and backed by a solid biotech company caught my attention. I will start by saying that Biogen is not a client of mine and the stock purchase was for my own private use.

As trial results began to emerge, I was taken aback by one very important element in the trial. The innovators had developed their own composite measure as a testing instrument for their own drug. Basically, the efficacy of the drug was being measured using metrics they had internally developed. They claimed their instrument by design had increased sensitivity when compared to the ones used by clinicians such as the Mini-mental State Exam (MMSE) and ADAS-Cog (Alzheimer’s Disease Assessment scale-cognitive subscale).

I agree that some metrics need to be updated and reflective of today’s widespread practices. However, the problem as I saw it, was their instrument had not been tested and quantified at large. Hence, their double-digit efficacy was based on their model and not a model that had a widespread adoption among clinicians. A bit like the fox guarding the hen house.

Advice I share with first time Entrepreneurs

In 2002, I was the recipient of the ProMontreal Entrepreneurs (PME) funding (start up capital coupled with guidance and support) for my then eponymous company, The Tendler Group, a medical market research agency. Fast forward to 2007, I was invited to sit on the opposite side of the table, as an Executive of the Selection Committee. How exciting I thought, to be able to listen to passionate and driven entrepreneurs pitch their businesses. As I enter my 11th year on the selection committee (kind of like a Dragon on the show Dragon’s Den), I continue to have the privilege of meeting, mentoring, some incredible Montreal based entrepreneurs.

 So… what have I learnt by sitting on either side of the table? Quite a bit:

1.     Not everyone is an entrepreneur. Sorry. Instinct, the nucleus of entrepreneurship, cannot be taught. I know it stings, but it’s the truth. The sooner a person realizes this, the better off they are. An innovative idea as great as it is does not mean the person who conjured it up is an entrepreneur. I don’t have a litmus test to share, but, sitting on a selection committee we can somehow sniff out the true ones. We just can.

2.     It’s never too late to start a business, it can be ‘too early’: Some entrepreneurs like myself garnered years of experience at other firms prior to branching out on my own, within the same industry. It allowed me to learn from others, anticipate weak points, learn management skills and mimic what worked well, while avoiding what didn’t. It also lent credibility, as clients knew me. Hence, logging in a few years at a few companies will only prepare and you and get you closer to your end goal. Subsequently, some of my best clients, were my former co-workers.

The 2nd type of entrepreneur that we see, are those who are entering industries for which they have little to no experience. It’s not to say that they won’t succeed. Look at all the disruptive industries that we see today, Casper mattresses, Warby Parker etc.… the founders had little experience in their respective industries but brought a fresh and a new perspective to rather stale industries that had not progressed in decades. Either way, timing of when one starts a business is critical. You must know when to move full throttle forward and when to hit the pause key. While many articles have been written on this topic, it truly comes down to instinct.

3.     A great idea but a poorly executed plan: This plagues many entrepreneurs. Coming up with a great idea, is great, but how will this translate into a business? What will the structure of the firm look like? What is the timeline? How will the financials look like initially and further down the road? What is the plan for the first 12 months? How will everything support this engine? Not every great idea translates into a company, and not every company has to have an amazing idea. Sometimes the simplest idea is the best. Improving on an existing service or product. A great idea poorly executed will rarely succeed. If you can’t properly execute the ideas, surround yourself with those who can.

 4.     Underestimating competitors: Putting down your competitors is the equivalent of a short person criticizing a tall person in order to feel taller. We see it all the time. Don’t bother as it only makes you look bad. Hopefully your competition will drive you to be better and stronger. Period.

5.     The Pitch: Within PME, entrepreneurs are allotted 15 minutes to pitch their business plan. As nonsensical as it sounds, plenty of entrepreneurs will waste a quarter of their time talking about how they came up with the nifty name company name, or how they met their partner years back. I always sit stunned thinking to myself, what a waste of precious time on such trivial information. More times than less, that same person is left short changed as when their time is up, they have not been able to properly showcase their business.

6.     Lastly, create your own Board of Directors. I am always impressed with entrepreneurs who build their own personal network of advisors. It shows they are willing to humble themselves and learn from others. I have yet to meet an entrepreneur who was not willing to help a fellow business starter. Create a circle of advisors with different talents and backgrounds and seek their guidance.

 For more information on ProMontreal Entrepreneurs please visit: https://www.promontrealentrepreneurs.org/

If We Don't Disrupt Our Industry, Someone Will

The health venture established by Amazon, Berkshire Hathaway, and JPMorgan Chase combined represents 1 million privately insured employees. They are only second to Walmart’s 1.1 million employees. The 3 companies which bring their scale and expertise to this endeavour, will pursue this through an independent company that is free from profit making incentives and constraints. While most details remain under lock, Dr. Atul Gawande, the Harvard surgeon named to run the initiative, has already pinpointed wasteful administrative costs, pricing, and the intermediaries in the healthcare system.

Amazon with its recent acquisition of PillPack, is well positioned to change the game by managing prescription and supplies for instance in patients with chronic health issues. A diabetic patient may opt to get all their supplies including their drugs from Amazon delivered to their doorstep. Couple this with integrative technology that monitors insulin levels and adherence, maybe some diabetic friendly food from Whole Foods, and you now have a personalized medicine program that could potentially  drive better medical outcomes.

While the venture will be geared towards employees of the 3 companies, it will make its innovations available freely to other firms, thus broadening its reach.

While still in its early planning stages, success will require a long-term orientation and talent that can execute such a large undertaking. Can these 3 business icons disrupt the current system? Some would argue they already have.

CancerSEEK® Test: Early Detection of 8 Cancer Types

Adapted from Dr. Peter Lin's evaluation of the CancerSeek® Test, a blood test measuring the levels of circulating proteins and mutations in cell-free DNA. 

Cancer cells are dying all the time, and some of their DNA will end up in the bloodstream. This CancerSeek® test looks for 16 of these cancer genes. Also, cancers make certain proteins, and so eight such proteins are also included in the test. The detection of these genes or proteins will tell us that there is a cancer; but where is it? With some sophisticated software to look at the patterns of which genes and which proteins, the type of cancer can be determined. For example, ovarian cancer will have different genes and proteins that light up compared with liver cancer. Therefore, this test can not only detect cancer, but also help identify which tissue is involved.

To test the “test,”  researchers looked at 1005 patients who had known cancers between stage I and III; non- metastasized. The patients were chosen who had one of the eight most common cancers, which included cancers in the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, and breast. The researchers stated that these eight cancers account for 60% of cancer deaths in the US in 2017.

Overall, the test was able to detect 70% of these eight cancers. However, there were differences in the detection rates for the different cancers. Ovarian and liver cancers were the best at 98%. Breast cancer was the lowest at 33%. This basically means that the researchers need to find a better gene or protein that can be used to identify that cancer.

Stage I cancers were detected at 43%, stage II cancers at 73%, and stage III cancers at 78%. Of the stage I cancers, liver cancer was detected at 100%, whereas esophageal cancer was the lowest, at 20%. This concept will change the face of cancer detection and management. The early detection will mean earlier treatment on smaller lesions or perhaps even on lesions that we could not even see on imaging. The most exciting aspect, though, is that this test could allow treaters to rapidly decide if a therapy is working or not. Imagine that a patient has the test and then a particular therapy is given. If it is working, the mutated genes should increase as the cancer cells are killed followed by a drop and then no more mutated DNA in the blood because the cancer has been eradicated. So, within weeks Oncologists would know if the treatment is successful or not. If the DNA does not drop, then the therapy is not working and a  switch to another therapy can be made quickly. This is dramatically different from the current method, which is to give the therapy, wait 3 months to do imaging to see if the lesion has reduced in size, and then decide if a change is needed. Valuable time is often wasted, and patients may have had to endure side effects without any benefit. So, a blood test will be revolutionary for the treatment of  patients with cancer.

I wish I had the answers: Pricing drugs for Rare diseases

How do you price a drug for a rare disease/ orphan status drug? The question that comes up time and time again. Truthfully, I don’t have the answer. Biogen feels that Spinraza is fairly priced at $750,000 for it’s first year of treatment. Maybe it is –maybe it’s not.

It begs the questions of how the industry, payors and the population as a whole, place value on health and quality of life. Moreover, if pharma companies are not given the band width to price high a drug for rare disease will they continue to pursue this avenue? Some rare diseases may have less than 5000 or even 100 patients in the world—does the public feel that a pharma company should dedicate 5-8 years of R&D and millions of dollars and not recoup this?

Do we allow disease modifiers to be priced higher than those that just manage symptoms or provide progression free survival? How do we price quality of life? Do we assign the same value to a person in their mid 30’s as we do to someone is their 70’s?

I take the case of a lady aged 62 that I know. She has been on a HER2+ agent for over a decade. A Stage IV HER2+ breast cancer patient with brain and bone mets at diagnosis, she was given less than a year to live. Her drug therapy is keeping her alive. Her diagnosis 10 years back shortened her much loved teaching profession. She now volunteers for free at a local public school twice a week assisting elementary students with special learning needs. Is their value to that? The money in Canada comes from the same pocket. Is she saving our government money by them not having hire a teacher to manage children with special needs at this particular school?   

How do payors decide what is acceptable? For instance, a cure for Hepatitis C drug is priced less than what a liver transplant would cost. Is that the model that we should be using? Do payors factor in a lifetime of medication, appointments etc... Is all this moot during an election year?

I wish I had the answers…

Drawing a Line in the Sand: 6 Lessons in Patient Market Research

It is very easy to dive deep into a market research project and lose sight of the fact that you are delving into someone’s life, their private space, and for some if not most, a sensitive topic. Here are 6 lessons that I have learnt over the years of conducting patient market research.

Lesson #1: You must draw the line somewhere in the sand

In all my years of conducting market research, and many of them in Oncology, I never accepted a mandate that entailed interviewing metastatic cancer patients. I never felt there was a grey area here. It was, and continues to be, quite black and white for me. There is no appropriate question to ask someone whose disease has been staged as terminal. Moreover, unbeknownst to many market research agencies, many cancer patients participate in market research for advocacy reasons. They think you are representing a pharma company that has a cure for their tumour type and they want in. What happens when you don’t?

Lesson #2: Patient privacy is YOUR #1 Responsibility

Sounds like a platitude…. right? I can’t tell you how many times I have shown up at a central venue, walked out of the elevator, and was greeted by a big poster stating “Hepatitis B Study-- Waiting area # 2”. It doesn’t take much to figure out that participants in Waiting area # 2 are not there for the <Shampoo study>. I never share the topic of the study with the facility if it is sensitive. Patients are told to simply mention my agency when the receptionist greets them.

Lesson # 3: Patients should know what to expect

Not all patients are seasoned participants in central venue interviews. If the study is a focus group, patients should be clearly told beforehand there will be other participants in the room. Some people are willing to share their story with a moderator, but, less so with a group of strangers.

Lesson # 4: Respect Patient Wishes

I have conducted patient research whereas I was asked to turn off the camera or draw the blind between the viewing and the interviewing room. Patients do not want to feel compromised or at risk of having their disease/sickness known to others. Moreover, as a moderator, if there is a chance that you may know the patient, have an associate conduct the interview. Imagine how a patient would feel walking into a room only to be interviewed by a moderator who lives 2 blocks away from them.

Lesson # 5: Sometimes you must go off script…

A few years back I tested packaging with patient suffering from a neurological condition that affected their dexterity. One of the many parts of the interview was to pass a blister pill pack to the patient and request they expel 2 pills. In meeting with the FDA’s regulations of childproofing all dispensed medications, the blister pack’s cardboard and aluminum lining was so thick that I without any dexterity issues, could hardly expel 2 pills.  I could see the patient’s frustration increase as the interview went on.  Most attributed their inability to complete the task with the worsening of their disease.  I went off script regardless of how others would view it and comforted the patients by sharing with them my inability to complete the task. You could see the immediate relief in their faces. I also let them know that thanks to their participation in the market research, the packaging would most probably be improved to better suit their patient cohort.

Lesson #6: Verify and then Verify Again

Checking a physician’s credentials is quite easy---patient credentials are another story.  Years ago, I was recruiting for a patient study and my first 3 recruits were all fraud and friends of one another!! The more questions I asked the more intense the lies.  Lies beget lies and by the time I was done screening the patient she was so ensnarled in her own lies that it was obvious to both of us that she was solely interested in the honoraria being offered. I had to disqualify the gang of 3 liars.

A two-prong system takes care of the latter. Thanks to the widespread use of smart phones, my recruiters always request a photo of the prescription itself. Moreover, patients are asked to bring their prescription to the interview. Lastly, patients are told a second screening may occur by a senior supervisor prior to the market research. While not fool proof, the latter does scare away those with bad intentions.