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Click the title above for a link to open the Pharmaceutical Commerce June 2023 issue in an interactive PDF format.

Pharmaceutical Commerce - June 2023 Issue (PDF)

’s June issue homes in on a variety of subjects, headlined by the ongoing changes impacting today's new-look pharma sales force. Factors explored include the industry's learning curve in digital adoption; hybrid selling; sustainable travel initiatives; and efforts to reduce operational costs. In his feature, Editor Emeritus Nick Basta points to “

” as the latest hot trend in this area, with the most notable example being ChatGPT. When it comes to technology driving sales force trends, a Numerof & Associates survey finds that 85% of respondents agree that “digital content and virtual meetings will remain significant components of the customer engagement model, even if access restrictions [some of which were imposed during the pandemic] are relaxed.”

Sustainability, on its own, continues to be an evolving and closely watched topic as well. In this issue, guest contributor Richard Peck shares what he thinks are realistic goals for the industry in achieving 

 across the supply chain. The goal, he notes, is to find the optimum balance between operational efficiency, product protection, and sustainability.

Taking a dive into the regulatory aspect of pharma—specifically market access and pricing—Ed Schoonveld details the latest in the implementation of the 

 in the US, including questions arising such as how the negotiated price will be set by the Centers for Medicare & Medicaid Services.

On another note, comprising this issue’s “In Focus” feature, Contributing Editor Suzanne Shelley offers readers an overview of the 

—a therapeutic category projected to rank the fourth highest in terms of global spending by 2027. Breakthrough drugs have helped to transform this space as of late, including the approval last year of Camzyos, the first and only therapy approved in the new cardiac myosin inhibitor class for the treatment of obstructive hypertrophic cardiomyopathy (oHCM), which is considered the most common hereditary CVD.

It’s amazing to think that we are already halfway through 2023! We hope you enjoy this issue, and look for plenty more noteworthy content ahead. Thanks for reading.

— Mike Hennessy Jr., President and CEO, MJH Life Sciences

The publication's June installment features a plethora of coverage, ranging from the learning curve in digital adoption to an overview of the CVD market. 

Operational Trends Surrounding the Pharma Sales Process

As I reflect back on the past few issues of 

 it seems as though they’ve been released at the perfect time, with 

’s February and April issues being unveiled right after Trade & Channel Strategies and the Healthcare Distribution Alliance (HDA)’s Distribution Management conferences, respectively. Our June issue follows that same trend, as LogiPharma Europe—held in April in Lyon, France—is barely in the rearview.

I was recently chatting with Group Managing Editor Michael Christel when it occurred to the both of us that the publication was in need of a "Conference Connect

type section that is fully dedicated to what the title suggests—a “behind-the-scenes” look inside the various conferences and trade shows that the editorial team attends. For that reason, readers will notice that this new component will become a consistent staple of future issues (as long as we happen to attend a show in that timeframe, of course). The first installment fdetails the various educational sessions that I attended at LogiPharma Europe. Something I did mention, but didn’t get into too much detail on, however, were the video interviews with SMEs in attendance that took place. I had the pleasure of sitting down with key opinion leaders from Johnson & Johnson, MSD, and Envirotainer to really pick their brains.

When I spoke with Niklas Adamsson, COO of Envirotainer, he offered his thoughts on the future of cold chain storage and transportation of pharmaceutical products. This activity has not only featured a rapid increase in demand for ultracold shipments (and more temperature ranges being shipped), but a need for solutions that can accommodate those ranges. Adamsson also discussed the importance of practicing sustainability by making shipments as efficient as possible when it comes packaging material and how much energy is used.

One could make the argument that the industry is well on its way in accomplishing these efforts. A Vantage Market Research 

 assessed last year’s global sustainable pharmaceutical packaging market to be worth $71.1 billion, and by 2030, it is expected to balloon to $190.2 billion, with glass in sustainable packaging (via bottles, containers, etc.) expected to account for over 38% of total sales by that same year.

Changing gears, we are delighted to announce the addition of a pair of new editorial contributors to 

's print coverage. I’d like to welcome the Patient Access Network (PAN) Foundation—a non-profit whose goal is to help Americans pay for medical procedures—and Bill Roth of IntegriChain—a business process platform and consulting company—to the 

 team. Both of their inaugural columns are featured in this issue. Please join me in welcoming them!

Nicholas Saraceno is Pharmaceutical Commerce's Editor. He can be reached at

As the brand looks to increase its coverage, Pharma Commerce welcomes a pair of editorial contributors to the team.

New Insights, Fresh Voices

The final week of April is always circled in 

’s calendar, as this marks the time in which LogiPharma Europe comes back into the fold. Held at the Centre de Congrès de Lyon in Lyon, France—about 300 miles south of Paris—the conference brings together executives in the supply chain, logistics, operations, distribution, and digital transformation spaces, all under one roof, while being touted as “the world’s largest life sciences supply chain event.”

I was given the opportunity to attend several sessions, some of which included:

“Driving Agility and Resilience: How Can You Derive Actionable Insights from Your End-To-End Suppliers to Maximize Adaptability and Secure Your Global Supply Chain Networks?” (keynote panel discussion)

“Digitalizing Patient Centricity: How Can You Leverage Innovative Tech to Ensure High Service Levels in the Face of Increasingly Complex Supply Chains?” (keynote panel discussion)

“Embracing the Sea Freight Opportunity: How Can You Overcome Recent Disruption Challenges to Drive Cost-Reduction, Reliability and Sustainability?” (panel discussion)

There were various fascinating tidbits that resonated from each of these, but a noteworthy one came during day two of the show at the aforementioned “Digitalizing Patient Centricity” session. The discussion, moderated by Kelsey Carvell, partner at Deloitte, featured Didier Jourdan, associate VP, global supply chain, Sanofi; Javier Martin, SVP, global strategy and development operations, Grünenthal; and Jens Schader, CVP, global supply chain management, Boehringer Ingelheim. They addressed multiple questions broken down by category:

Where would you place your company on the spectrum of involvement with personalized medicine, and what are the factors your company is evaluating as it develops a patient-centric strategy around these products?

 How are you managing to drive access and patient-centric operations in lower-volume and/or harder-to-reach regions?

 How is the next generation of customized medicines—such as cell and gene therapy—driving patient-centric operations across the industry?

 How are you building resilience across your supply chain and with contract manufacturing organizations (CMOs) to guarantee availability of medicines, given demand fluctuations in key markets?

Can you provide an example of how your company is aligning patient-centric strategy with environmental, social, and governance (ESG) goals?

had a filming stand located right outside the exhibit hall, which was a prime location for recording video interviews with subject matter experts. Among the executives we sat down with were Wayne Rothman, VP, value chain management, Johnson & Johnson; Frederic Brut, head of supply chain, Eastern Europe, Middle East, and Africa and Asia-Pacific, MSD; and Niklas Adamsson, chief operating officer of Envirotainer.

Topics that were explored ranged from ways to better build digital capabilities into workflows, to the future landscape of cold chain storage and transportation. You can catch these interviews along with other recent show coverage at pharmaceuticalcommerce.com/latest-conference. We plan on making these event highlights a consistent staple in future issues of 

, so stay tuned for where we will end up next.

A trip to Eastern France for LogiPharma Europe 2023.

The Lowdown on Logistics

In the US and Europe, there is quite a bit of movement on the market access front. The debate continues regarding the European Commission’s plans to shorten effective patent lives by two years unless a drug is launched in all 27 EU countries within two years of European Medicines Agency (EMA) approval. However, this edition of 

will focus on the evolving Inflation Reduction Act (IRA) implementation in the US.

The March 15 Centers for Medicare & Medicaid Services (CMS) guidance 

 provided some clarity, but many questions remain. For an update on IRA and a discussion on the elements, I am referring to Sean D. Sullivan, PhD’s 

). I will discuss some high-level implications.

The process for identification of the “negotiated” Medicare Part D and later Part B drugs is clear. The penalties for not negotiating are also clear and extravagant. The main questions are how the negotiated price will be set by CMS, and how it will impact pricing and formulary access of competitor drugs.

CMS will set a maximum fair price (MFP) for each drug molecule that is on the negotiation list. So far, it is known that the upper limit of MFP is the lower of the current negotiated price (Part D) or average sales price (ASP, Part B), and a percentage of the average manufacturer price (AMP), which ranges from 75% for small molecules between nine and 12 years after FDA approval, to 40% for all drugs beyond 16 years of approval. There is no lower limit, the process is confidential, and the penalties for not accepting CMS demands appear to be excessive. CMS has a lot of flexibility in its approach, as the law only excludes the use of metrics that result in a different valuation for elderly versus younger populations.

The focus seems to be on comparative effectiveness, manufacturer ROI, and potentially international price comparisons. At first glance, comparative effectiveness seems a fair criterion, but the experience in Germany shows that the definition of a comparator can easily be used to stack the cards in favor of lower-cost generics when not giving due consideration to effectiveness across populations, individual patient differences, and tolerability. What will be an accepted way to demonstrate differential value in the later stages of the life cycle, and what will be deemed significant? Will real-world data be accepted?

2. How will price and formulary status of drugs that are competing with the price-controlled drugs be impacted?

When a Medicare Part D plan starts implementing a, for example, 60% discount for drug A as a result of its determined MFP, how will they manage formulary listing for drugs A and competing (newer) drugs B and C that are in the same drug class? Will managed care plans be able to extract significant additional discounts for drugs B and C as the competitive balance has been distorted in favor of the now cheaper drug A? Will plans be tempted and able to force additional rebates for drug A?

Meanwhile, politicians are eager to build on the political IRA success with various partisan and bipartisan initiatives that take IRA a few steps further. As an example, on April 24, Sen. Klobushar 

 to change drug negotiation eligibility to five years after FDA approval and to accelerate the number of drugs up for negotiation. While these new initiatives are unlikely to pass the House, it needs to be a continuing wake-up call to the industry that there is a lot of energy in Congress to further control prescription drug pricing.

Engage in scenario analysis to guide development choices and commercialization decisions for individual drugs and portfolios.

Step-up communication capabilities and efforts beyond lobbying to politicians. The economics of pharmaceutical development is complex, but we need to agree on securing funding for innovation while ensuring that patients have access to the drugs.

Ed Schoonveld is a value and access consultant, and author of The Price of Global Health.

The latest on its implementation—and the implications for biopharma.

IRA Journey Update

Several important and historic reforms to the Medicare program are in sight, thanks to the passage of the Inflation Reduction Act (IRA) in August 2022. For the millions of patients living with life-threatening, chronic, and rare diseases, these reforms can’t come soon enough. But we also know, for far too many, challenges in affording their out-of-pocket prescription medication costs will continue.

As a result of the IRA, patients’ liability for 5% of the cost of their medication in the catastrophic phase of their Medicare Part D benefit will be removed beginning in 2024, resulting in an annual Part D cap at the catastrophic threshold, equal to about $3,250 in out-of-pocket costs. In 2025, this cap is lowered to $2,000. Additionally, in 2025, health plans will be required to offer individuals the opportunity to opt-in to a “smoothing program,” enabling them to spread their out-of-pocket costs over the course of the year. The impact of these reforms on patients’ ability to afford their treatments will be significant and should be celebrated.

However, we hear every day from patients about how these reforms are critical steps toward improving access. Many also share that the cap at catastrophic in 2024 and the $2,000 cap in 2025 will continue to present affordability challenges for them and others. That’s why, in the months following the passage of the IRA, the PAN Foundation conducted a national poll to hear directly from patients about the potential impact the reforms will have on them.

According to our poll, about 75% of adults said that it would be difficult to afford $2,000 in out-of-pocket prescription costs each year. Concerns were especially high among Black and Hispanic adults, adults with incomes of less than $50,000, and adults with chronic or rare diseases. For many, these continued affordability challenges may result in having to make difficult decisions—such as choosing between taking their medications as prescribed or buying less food for their families.

In addition to hearing directly from patients, we also wanted to better understand the potential impact of these new reforms based on existing data. That’s why PAN commissioned research by Avalere Health to examine the projected beneficiary utilization and spending by Medicare Part D beneficiaries under the new reforms. The Avalere analysis found:

More than 2.6 million non-low-income subsidy Medicare Part D beneficiaries will have out-of-pocket spending high enough to reach the new $2,000 annual out-of-pocket cap on prescription drugs in 2025, the year it goes into effect.

Additionally, about 800,000 beneficiaries in 2024 and more than 200,000 beneficiaries in 2025 will spend more than 10% of their income on prescription medications each year.

A higher share of beneficiaries who qualify for Medicare based on disability, as well as greater shares of Hispanic and Black beneficiaries, will have high spending levels early in the calendar year.

Paired with our national polling, these findings confirm what we already suspected—even with the Medicare reforms in place, many patients will still face real challenges affording their out-of-pocket Rx costs. To further illustrate this point, we want to introduce you to a real-life patient facing affordability challenges, George Valentine (view more here: https://bit.ly/42T5qky).

George is a retired, 71-year-old Medicare beneficiary living with chronic lymphocytic leukemia. While he acknowledges that the impending $2,000 annual cap will be helpful, he knows it will still be a significant burden for those living on a fixed income, like himself. He reminds us that patients are facing a whole host of other healthcare-related costs. For George, last year, this included the cost-sharing requirements associated with his 60+ physician office visits and the 150+ labs and diagnostic tests he underwent.

As we reflect on the millions of patients across the country like George, we must recognize the critical role charitable patient assistance foundations will continue to play. Because until everyone can get the healthcare they need and deserve, our work is not done.

1. PAN Foundation, “National Poll: Many Adults Will Struggle to Afford Medications Even with Medicare Reforms,” 

https://www.panfoundation.org/national-poll-many-adults-will-struggle-to-afford-medications-even-with-medicare-reforms

2. PAN Foundation, “Despite Historic Medicare Reforms, Charitable Assistance Programs Still Critical for Many,” 

https://www.panfoundation.org/despite-historic-medicare-reforms-charitable-assistance-programs-still-critical-for-many

3. PAN Foundation, “George Valentine: The Need for Predictable Out-of-pocket Costs,” 

https://www.panfoundation.org/georges-story

Kevin L. Hagan is President and CEO and Amy Niles is chief advocacy and engagement officer; both at PAN Foundation.

The Medicare Part D cap in 2025 won’t solve patients’ need for financial assistance.

Addressing Rx Affordability

Back in the mid-2000s, my management team made the rounds with industry leaders of healthcare payers, pharmacies, and distributors to alert them to a trend we saw. The response, however, was denial. We were attempting to alert them to a major seismic shift in the pharmaceutical market: new products coming to market were very different than the primary care brands and generics that our industry had nurtured for the past century, and we all needed to get ready for change.

The extreme examples driving the change were precision medicines, such as cell and gene therapies and orphan and rare drugs—with patient counts of less than 100 to less than 10,000, and price tags in the hundreds of thousands if not millions of dollars. We recognized these products didn’t fit into the large decaying legacy payer, pharmacy, and distribution models that formed in the 1980s and '90s.

In part, we were curious to know how these channels would evolve to embrace the new science but also to provide a heads up so the channels could begin to think about what might need to evolve and how they would accomplish their evolution. The lack of foresight—and inability to openly admit—that the industry was changing was disheartening because it meant that our manufacturer clients would have to design new models to accommodate the new realities of uber-low patient counts, exorbitant prices, payer hurdles like we’d never seen before, and complexities of therapy management.

We even had one executive tell us, “You’re going to have to pry our [historical] business model out my cold dead hands.” Within 10 years, that executive was no longer with the industry, let alone the multi-billion-dollar company he used to lead.

The point in this history lesson is that 20 years ago, Blue Fin Group saw a phenomenon developing that changed how products were commercialized depending on their “product archetype.” Fast forward to today, we track and analyze 10 archetypes—traditional brand, generic, vaccine, specialty lite, specialty generic, biosimilar, specialty (self-administration and healthcare provider administration), orphan and rare, cell and gene, and digital. When developing commercialization strategies, we separate and segment these archetypes because the payers, providers, pharmacies, patients, and physical flows are significantly different for each one.

A shelf life to the ‘copy-and-paste’ model

Having now worked with more than 450 pharmaceutical manufacturers, most struggle to visualize these segmentations and instead apply a “copy-and-paste” model to their contemporary commercial strategies based on the old models that gave success once upon a time. If we go back to a more simplistic time prior to the '80s, the pharmacy world was primary brand and primarily a cash-pay market. Pharmacy benefit managers (PBMs) did not exist. Generics had not really penetrated the market yet because there wasn’t a significant need. The concept of specialty was mainly around blood products, fertility, and HIV.

As PBMs came to power and the generics improved their quality and availability, the '90s and '00s were filled with rising brand prices combined with more generics that brought significant savings to plan sponsors and enhanced margins to payers, pharmacies, and distributors. But like most good ideas, there was a shelf life. The money to be made in generics was primarily in the first six to 18 months of introduction, and as long as new-item generics kept coming to market, all was well.

2012 marked the pinnacle of the “primary care LOE wave,” and 2016 marked the end of the party. The stocks of PBMs, retail pharmacies, and distributors took massive hits. Executive teams fully changed over. Business models were destroyed, not because of mismanagement or competition, but simply because one archetype took over from another. And this has been the trendline.

Here in 2023, we are facing the next wave of archetype transition, known as the “specialty LOE wave.” It features the expansion and explosion of proteomic and genomic medicines, and is hitting at a time of massive payer and regulatory reform. With more than $228 billion worth of specialty products set to lose exclusivity on their patents from 2023 to 2028, there is significant consideration for what this might mean. Many channels are counting on the success of specialty generics and biosimilar products. But traditional brand or reference products aren’t necessarily sitting back and converting markets like they did for primary care. The successful companies that are either defending their market or penetrating are realizing that even specialty generics and biosimilars need many elements of a traditional brand commercial strategy. These products still face prior authorizations, step edits, patient out-of-pocket hurdles, and other headwinds. For example, does interchangeability matter on a biosimilar if the product is not covered by the payer? That is what several adalimumab manufacturers are learning as they get to launch their generic products against the juggernaut Humira.

The market is experiencing similar trends now with so-called "specialty lite" products priced between $5,000 and $25,000 annually; there is no pharmacy that will support these products. They are too complex for retail pharmacy, which is 92% generic, and they are not priced high enough to be considered by specialty pharmacy. It’s simple: the economics don’t work for pharmacy, or at least not the current pharmacy models. Mind you, this is where e-commerce and digital pharmacies are supposedly coming to the rescue, but they have their own set of challenges with payer access, coordinated care, and the splintering of the patient journey by exacerbating the growing issue with polypharmacy.

So, what are the implications to industry? In a word: complexity. It means that each product, and, therefore, every commercial strategy, is essentially a snowflake of a business model—meaning that no two products or commercial strategies can be the same. If your team, advisors, or consultants are approaching you with “trust me I’ve done this for X number of years,” run, don’t walk away. With highly varied therapeutic areas, benefit designs, payer mixes, patient counts, payer headwinds, prescribing requirements, and regulatory headwinds, all the pieces of a commercial strategy need to align. The simple implication to pharmaceutical manufacturers is that copy-and-paste or ChatGPT-generated strategies aren’t going to get the manufacturer too far.

The ability to see even one to three years into the future has become a challenging task with huge downside risks. And the customers of pharma manufacturers—the payers, PBMs, pharmacies, and distributors—aren’t going to provide direction or insight as they themselves are figuring out how to survive this new world.

A practical first step is to consider the current and future portfolio. What therapeutic areas, archetypes, and benefit structures are likely in the development or M&A plans? A line we have been saying around the office recently is, “If the manufacturer is lucky enough not to be handed a complete response letter (CRL), what are the chances of a positive gross-to-net?” Enter the golden age of the CFO.

For the last two to three decades, pharma manufacturers have operated in commercial silos with marketing, field sales, payer and market access, channel and distribution, and patient support services operating as separate business units making decisions that have profound implications to net revenues and government prices. We see this mindset coming to an end and more fiscal planning and projections being the future.

But this is met at a time when payer, pharmacy, group purchasing organization (GPO), and distribution channels are fighting quarter by quarter to hold on to their own business and margin. That’s why we are coining the phrase that “fight for the dollar” is the new “flow of the dollar.” Models that show product simply moving from a third-party logistics provider (3PL) to a wholesaler, to a pharmacy, and to a patient with payer coverage and happy providers are only true for a small and shrinking portion of the market.

Look to the future and ensure you and your commercial teams are as educated as possible on industry and commercialization trends, along with new concepts of distribution and patient access, and, importantly, stay nimble. Stay tuned for my next column where we’ll dive deeper into the flight for the dollar and what you can do to prepare yourself for commercialization success.

Bill Roth is the SVP of IntegriChain’s consulting business, which includes Blue Fin Group, a strategic consulting company he started in 2001, and the existing IntegriChain operational consulting business.

New PC column explores commercialization trends and how pharma can adjust to the new squeeze of market, regulatory, pricing, and gross-to-net pressures.

Channel Fragmentation and Diversifying Product Archetypes

The cardiovascular disease (CVD) pharmaceutical treatment market has traditionally involved a mosaic of modalities and medications, as, after all, heart disease is not just a single affliction but rather a group of disorders.

 This segment includes conditions such as:

Atrial fibrillation or arrhythmia (abnormal heart rhythm)

Chronic ischemic heart disease (reduced blood supply to the heart)

Stroke (interruption of blood flow to the brain)

Heart failure (inability to pump blood adequately)

Angina (caused by insufficient oxygen flow to the heart)

Myocardial infarction (interrupted blood flow damaging heart muscle tissue)

As such, no single issue defines the complex landscape in CVD. Despite the pace of generic entrants and the impact of poor adherence to therapy on clinical outcomes, other forms of innovation are continuing to generate enthusiasm in the space. For instance, drug developers continue to bring breakthrough therapies to market, while the use of artificial intelligence (AI) and machine learning (ML) techniques are helping physicians to make more accurate and timely diagnoses and are helping to inform efforts to repurpose existing CVD drugs for new indications or pair them in opportunistic drug-drug combinations.

According to IQVIA Institute’s recent publication “The Global Use of Medicines 2023: Outlook to 2027,” CVD medications are projected to rank No. 4 in the list of top 20 therapy categories in 2027 (in terms of global spending), behind oncology, immunology, and diabetes. CVD therapies generally fall into several buckets, including:

Statins to lower low-density lipoprotein (LDL) cholesterol

Beta blockers to lower blood pressure, heart attack, and heart failure

Angiotensin-converting enzyme (ACE) inhibitors to reduce heart failure and blood pressure

Calcium channel blockers to reduce the workload of the heart

Angiotensin II receptor blockers to reduce blood pressure

It could be argued that the stakes are high in CVD. Heart disease remains the leading cause of death in the US, according to January data published by the American Heart Association (AHA).

 Meanwhile, according to the report, between 2018 and 2019, direct and indirect costs of total CVD were $407.3 billion.

While the CVD space was once the place where blockbuster drugs routinely planted a flag—with heart medications such as Crestor, Lipitor, Vytorin, and others practically being household names—the proportion of generic medications in CVD is expected to reach 44% of the market by 2028 (up from 32% in 2018), according to IQVIA. And the number of generic launches continues to outpace new product launches in CVD. IQVIA projects 137 loss of protection and generic entry events in CVD between 2019 and 2028—compared to 25 new CVD therapies approved in the same period.

Despite asymmetry in the proportion of generics to branded therapies entering the arena, “the past decade has also been associated with a boom in new agents and refined drug capabilities in cardiovascular and cardiometabolic care,” notes Alla Shargorodskaya, MD, senior director, therapeutic strategy and innovation, at Syneos Health.

Recent groundbreaking therapies that target the molecular basis of the disease are helping to transform the CVD arena, in terms of their ability to reduce morbidity and mortality, improve quality of life, and help some patients to avoid costly, invasive surgical interventions, trips to the emergency room, and hospital re-admissions. One recent example is the 2022 approval of Camzyos (mavacamten) from Bristol Myers Squibb (BMS). It is the first-in-class—and to date the only—therapy approved in the new cardiac myosin inhibitor class for the treatment of obstructive hypertrophic cardiomyopathy (oHCM), the most common hereditary CVD.

Prior to the approval of Camzyos, patients with severe oHCM typically required an open-heart surgery or ablation procedures, notes BMS. The company acquired Camzyos as part of its $13.1-billion buyout of MyoKardia in 2020. A second investigational therapy in the cardiac myosin inhibitor class—aficamten from Cytokinetics—is currently undergoing clinical trials.

“Sodium-glucose co-transporter inhibitor therapies (SLGT2) for the treatment of heart failure have also given many a cause for celebration,” says Pierantonio Russo, MD, chief medical officer, EVERSANA. They are designed primarily for patients with heart failure (with and without diabetes) who have a history of frequent hospitalization. “This class of drugs are proving to reduce hospitalization in these patients, and they’re offering a lot of hope for these patients,” he adds.

Meanwhile, renewed attention to resistant systemic hypertension is also encouraging. “Results from the recent BrighHTN trial (involving investigational drug baxdrostat) provide evidence that selective inhibition of aldosterone synthase leads to a substantial dose-dependent in blood pressure among patients with resistant hypertension,” explains Russo. In January, AstraZeneca entered into a definitive agreement to acquire CinCor Pharma, which produces baxdrostat.

In a parallel lane, it has been more than 30 years since a new antihypertensive agent with a new mechanism of action has been approved. In December 2022, Swiss pharma company Idorsia submitted a new drug application to FDA for its experimental therapy aprocitentan, a dual entothelin receptor antagonist (ERA), for patients with difficult-to-control hypertension.

“Aprocitentan is a potential novel and effective agent targeting a currently unopposed pathophysiologic pathway, and market authorization is expected as uncontrolled blood pressure is one of the most common risk factors for major cardiovascular events,” notes Shargorodskaya.

She adds that the "highly efficient" PSCK9 inhibitors are also making a significant impact in treating hyperlipidemia, without the feared muscular side effects or potential concerns of diabetes and dementia. There are currently three drugs in this class: Praluent (alirocumab) from Regeneron, Repatha (evolocumab) from Amgen, and Leqvio (inclisiran) from Novartis.

Physicians often have trouble identifying and diagnosing patients with a particular form of heart disease called wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), an under-recognized, life-threatening condition that results in progressive heart failure. Pfizer has developed a novel prediction algorithm

 (working in conjunction with researchers at the Northwestern University Feinberg School of Medicine and the Brigham and Women’s Hospital) that can help to stratify patients and identify those who are at risk of wtATTR-CM.

Pfizer’s novel model leverages AI and ML—and has been validated using medical claims and electronic health records (EHRs) data—to identify symptoms of wtATTR-CM earlier. Unlike conventional statistical approaches, ML can more efficiently evaluate complex interactions across multiple 

input predictors, and in this particular model, was used to automate the suspicion of wtATTR-CM based on associated clinical conditions, according to the company.

 reports that the model performed with 87% accuracy in predicting patients with heart failure associated with wtATTR-CM, enabling healthcare providers to identify and appropriately diagnose patients with the condition wtATTR-CM earlier and with greater accuracy. This is particularly important to allow for initiation of therapy earlier in the trajectory of this life-threatening condition.

To make the novel prediction model more easily accessible to physicians, Pfizer also developed and launched EstimATTR, a web-based educational tool that US healthcare providers can use to help estimate the probability that a hypothetical patient with heart failure may have wtATTR-CM.

AI and ML are also being explored to support faster, more accurate diagnosis in CVD by identifying clinically relevant patterns from large, complex datasets (not just EHR and claims data, but data from wearable sensors and monitors, CT scans, and more) and creating actionable outcomes.

“In the near future, it will not just be some companies—it will be most companies­—that develop analytic algorithms to support their drugs,” says John Doyle, DrPH, group vice president at Exponent and adjunct assistant professor at Columbia University’s Mailman School of Public Health.“I expect that we’re going to see a lot more of that—developing predictive models based on AI and ML that are approved like a companion diagnostic—to support CVD drug development and market access.”

Putting real-world data and evidence to work

Separately, a recent EVERSANA study used real-world data (RWD) and advanced analytical techniques helped to identify patients with heart failure and fluid overload suitable for subcutaneous furosemide infusion in the outpatient settings rather than inpatient settings.

“This data allows us to more precisely identify the right patient population, something that was challenging in the past,” says Russo. “What makes this so meaningful is that subcutaneous furosemide infusion may substantially improve the care of patients with heart failure by keeping them at home rather than treating them with frequent visits in an emergency room or hospital.”

Using advanced techniques and RWD sources, “we can now prove in real-time just how effective the results are for patients,” continues Russo. “In this new climate of value-based care and outcome-based reimbursement, pharmaceutical companies must continuously demonstrate the impact of their CVD assets on reducing the total cost of care per patient, and reduce the need for more costly interventions.”

“Real-world studies help maintain access and demonstrate continued value of the product by providing evidence on comparative clinical effectiveness and costs, long-term outcomes data, patient safety data, and patient adherence and utilization data,” adds Shargorodskaya. “Continual observation of disease epidemiology, treatment patterns, and outcomes in the real world can also help to accelerate evidence generation that is needed to add indications and support label expansion for specific cardiovascular products.”

In CVD and other disease settings, real-world evidence (RWE) insights are increasingly being used to effectively articulate disease burden and demonstrate the long-term value of a therapeutic intervention and help justify premium pricing and coverage decisions.

“To do this, drug developers must strive to connect medication adherence with tangible outcomes, such as reduced hospitalizations or cardiac events, and develop comparative clinical effectiveness and cost data,” says Doyle.

The BMS/Pfizer alliance that brought the direct-acting anti-coagulant Eliquis (apixaban)—a therapy to reduce blood clots and the risk of stroke—to market was considered a pioneer in the use of RWE to not only expand the scientific understanding of a drug after market launch, but to use the clinical findings to demonstrate the full value of the product in every day clinical practice. By linking long-term adherence to the ability to offset other, more costly interventions, the companies were able to provide an economic case for switching from warfarin (a leading alternative therapeutic option) to Eliquis, and then use the findings to inform pricing, reimbursement, and market access negotiations.

The work of the BMS/Pfizer alliance “remains the gold standard for how a CVD therapy can differentiate itself among regulators and payers based on RWE generated post-launch, and still serves as an exemplar for other drugmakers in other therapeutic classes,” says Doyle. “It was novel at the time, and many companies are still trying to emulate what this partnership has done: they proved with long-term RWE that Eliquis could lower the risk of stroke, with fewer incidents of bleeding compared to warfarin. That’s been a massive differentiator that helped to extend the lifecycle of the product.”

As part of the BMS/Pfizer alliance, the companies also partnered with FitBit to develop an algorithm to be used with their sensor that could identify patients who are at risk of atrial fibrillation (Afib). “In this context, sensor-derived insights can help to stratify patients based on risk and identify potential candidates who have elevated risk of Afib earlier (particularly those in disadvantaged communities),” notes Doyle. “While such findings are still subject to medical follow-up to verify and validate the finding, the opportunity to accelerate diagnosis is beneficial to patients, providers, payers, and manufacturers.”

Efforts to pair various CVD medications with mobile sensors and wearable devices provide novel opportunities to generate actionable data that can help to improve diagnosis, support adherence objectives, and generate RWE to strengthen the brand’s value proposition and likelihood to grow. “Progressive pharma companies are leaning into developing and deploying these digital health technology tools to differentiate their core portfolio, as well as add new products to the CVD ecosystem,” says Doyle.

Drug repurposing—whereby approved therapies are able to secure label expansions into different therapeutic indications—offers another route for makers of CVD medications to prolong the lifecycle of their branded therapies. Historically, such opportunities have been driven by knowledge of underlying disease mechanisms or by serendipitous observation of clinical benefits in other patient populations—rather than by systematic efforts to prospectively match an existing drug to a new indication.

However, there is ongoing innovation in computational analysis and predictive modeling that helps stakeholders to systematically screen drugs for disease-modifying activities, ones that are in search of repurposing opportunities that could address unmet medical need and create new opportunities for aging drug franchises. The newer approach relies on extensive phenotyping of a drug’s effect at the level of patient care—gleaned from EHR data—and using modeling systems to identify compounds that ameliorate disease phenotypes.

A recent example of drug repurposing is helping patients with another form of CVD, heart failure with preserved ejection fraction (HFpEF). “HFpEF has recently been recognized as the single greatest unmet need in cardiovascular medicine,” says Shargorodskaya of Syneos. “People with HFpEF also have a higher prevalence of hypertension, diabetes mellitus, chronic kidney disease, atrial fibrillation, and non-cardiovascular comorbidities (such as obesity and chronic obstructive pulmonary disease), compared with those with heart failure with reduced ejection fraction (HFrEF).”

The SGLT-2 inhibitor Jardiance (empagliflozin) from Boehringer Ingelheim—originally approved to lower blood sugar levels in patients managing type 2 diabetes—earned an expanded FDA approval in 2022, for the treatment of patients with heart failure independent of left ventricular ejection fraction (LVEF), and for the treatment of patients with HFpEF.

Shargorodskaya points out that empagliflozin was initially a drug for the treatment of patients with diabetes, but has demonstrated notable and nearly unprecedented benefit for cardiovascular risk reduction in HFpEF patients.

“In cardiology, one of the most recent celebrated examples of drug repurposing is the use of new antidiabetic drugs, specifically SLGT2 inhibitors, as they have been shown to reduce hospitalization in patients with heart failure even if they don’t have diabetes,” adds Russo of EVERSANA. The company is collaborating with Every Cure to carry out drug repurposing studies.

Meanwhile, “creating beneficial drug combinations is another strategy that can add therapeutic value and enhance the commercial life of today’s CVD drugs,” says Shargorodskaya. “Fixed drug-combination strategy helps to fill the therapeutic gap for patients who are unresponsive to monotherapy, can help to address comorbidities, and improve patient convenience.” This strategy can also help to extend the lifecycle of one or both drugs in the combination.

1. Davies, C.; Yashwardhan, S. Heart Disease Market Forecasts, IQVIA blog. October 17, 2019, 

https://www.iqvia.com/blogs/2019/10/heart-disease-market-forecasts

2. Heart Disease and Stroke Statistics — 2023 Update. American Heart Association. January 25, 2023, 

https://professional.heart.org/en/science-news/heart-disease-and-stroke-statistics-2023-update

3. Pfizer’s Novel Prediction Model, Derived from Machine Learning, Shows Robust Performance for Identifying Heart Failure Patients At-Risk for Wild-Type Transthyretin Amyloid Cardiomyopathy, a Rare and Life-Threatening Condition. Pfizer press release. May 11, 2011, 

https://www.pfizer.com/news/announcements/pfizers-novel-prediction-model-derived-machine-learning-shows-robust-performance

4. Huda, A.; Castaño, A.; Niyog, A.; et al. A Machine Learning Model for Identifying Patients at Risk for Wild-Type Transthyretin Amyloid Cardiomyopathy. 

https://doi.org/10.1038/s41467-021-22876-9

5. Abdelsayed, M.; Kort E.J.; Jovinge, S.; Mercola, M. Repurposing Drugs to Treat Cardiovascular Disease in the Era of Precision Medicine. 

https://doi.org/10.1038/s41569-022-00717-6

While generics and adherence challenges are keeping drugmakers up at night, breakthroughs in the pipeline coupled with innovative uses of artificial intelligence and machine learning techniques are bringing optimism to the cardiovascular disease space.

Innovation in Heart Disease: A Deep Dive

Like many other aspects of healthcare, pharmaceutical sales and marketing practices have been changed by the COVID-19 pandemic. The most noticeable initial effect, of course, was the rapid diminishment of face-to-face sales encounters. Pharma sales positions were cut back (ZS Associates notes that they have now rebounded to around 81,000 positions in the US), while video calling went up, but overall healthcare utilization plummeted as fewer patient visits with doctors’ offices occurred and fewer elective procedures were performed. According to IQVIA’s “The Use of Medicines in the US 2023,” prescribing levels (excluding COVID vaccinations) only recovered in Q4 2022 to the level they had in the first few months of 2020.

Overall, the pandemic accelerated many changes that were already occurring prior to 2020. The pharma industry had been adjusting to a rising number of “no-see” physicians (who were also increasingly becoming health system employees rather than independent practitioners). Health system consolidation was centralizing prescribing and formulary decision-making. And the industry itself has moved more deeply into specialty pharmaceuticals, which have a more complex prescribing profile and need a wide range of diagnostic or ancillary services to complete a therapy decision.

Meanwhile, the service providers to the pharma industry for sales and marketing support have continued to evolve. Video conferencing services have become routine. IT developers of sales force automation tools are expanding their range of capabilities. The latest hot trend—the emergence of “generative AI” as best exemplified by a system called ChatGPT—is attracting attention and investment from a range of technology organizations. (ChatGPT, whose current platform version is GPT-4, is owned by a nonprofit company called OpenAI Inc., which has a commercial arm that has attracted over $10 billion from Microsoft.)

Numerof & Associates, a St. Louis healthcare consulting firm, finds that 85% of survey respondents agree that “digital content and virtual meetings will remain significant components of the customer engagement model, even if access restrictions [some of which were imposed during the pandemic] are relaxed.” The survey, “The Future of the Commercial Model: Post-Pandemic Insights,” was performed in late 2022 and follows on a similar survey in 2020. In that year, many respondents expected the industry—and its commercial models—to revert back to pre-pandemic forms, but now, there is a consensus that traditional ways of doing business are history.

Another market-research firm, Gartner, issued a report on life sciences customer relationship management (CRM) in late 2022, noting that the drive toward more digital capability, and the changing role of sales reps, has been gestating for a long time, but is now a more urgent need. "Gartner introduced the idea of a 'concierge' sales representative, which is a digitally enabled sales representative, a decade ago. However, it never reached mainstream adoption, as many life science brands preferred not to change their business models for fear of revenue disruption," the report said. "The pandemic has changed that calculus. Digital 'concierge representatives' won’t be asked to drop off samples or engage in two-minute elevator speeches, but rather, will invest significant time nurturing long-term relationships with their customers. Face-to-face engagement will change from the inside-out, ‘I have a presentation for you,’ to the outside-in, ‘What do you need from my organization, and how can I facilitate that?’”

Five recurring themes emerge from market studies like these and industry commentary:

The need for managing both face-to-face and digital interactions, preferably with a unified system that can accommodate call reports or feedback from any channel. The older concept of “multichannel” marketing has given way to today’s “omnichannel” approach.

The emergence of so-called hybrid reps (adept at multiple channels) and/or the development of inside-sales or call centers that complement field sales. This trend also takes advantage of the employee trend toward work-from-home arrangements.

The availability of more, and more in-depth, data on both patients and prescribers, the former to analyze market potential and performance, and the latter to recognize key influencers among healthcare professionals (HCPs) and to feed that into the reps’ sales plans.

The steady growth of artificial intelligence/machine learning (AI/ML) capabilities, starting with an earlier era of CRM-generated “recommendations” for sale reps’ actions, to the current “next best action” for reps or for marketing managers, to the future potential of generative AI like ChatGPT and similar IT tools.

The growing importance of consolidated health systems and pharmacy benefit managers, whose decisions on physician access, therapy choices and drug formularies dictate market access for manufacturers. This business condition, in turn, drives the need for key-account management teams in sales forces.

“Back in the day, ‘multichannel’ simply meant putting out your content in whatever channel you could—via print, on a website, in an e-mail, and so forth,” says Parker Richardson, VP, omnichannel strategy and operations, Astellas Pharma. “The shift to omnichannel is twofold: understanding, via deep analytics, the journey that a prescriber is on and helping to orchestrate that journey; and then recognizing the content that would benefit the prescriber and delivering it.” Rather than tailoring content to multiple channels, he says, the process should begin with understanding what the prescriber needs to know, and then delivering it via the channel that prescriber prefers.

The generally acknowledged market leader in life sciences CRM is Veeva, which states that it reaches 80% of the global market for life sciences sales reps (and even more in the US). Veeva pioneered cloud-based CRM in the mid-2000s, and has also grown a substantial business in managing IT needs for clinical research. Late last year—and in more detail at its recent Commercial Summit in Boston—it announced that it was leaving the platform it was built on, Salesforce.com, and building its own, called Vault CRM.

Salesforce.com happens to be broadly used in CRM in many industries and types of business, and competitors to Veeva, including IQVIA (and Salesforce itself, in certain applications), use that platform. Veeva says that this will be a seamless transition for users, but as Paul Shawah, EVP, commercial strategy, puts it, “Customers can choose a ‘lift and shift’ approach to transition from the old platform to the new one, or a ‘refresh’ approach to revamp their sales structure while transitioning.” The transition will begin in early 2024, and continue until 2030, when Veeva’s partnership with Salesforce.com will expire. At the same time, Veeva is moving closer to Microsoft, by enabling Microsoft’s Outlook (for email) and Microsoft 365 (the former Microsoft Office) to be seamlessly integrated with Veeva CRM.

Veeva announced some significant new offerings at that Boston meeting. One is a service center extension, tailored to supporting inside sales teams while linking seamlessly to Veeva CRM. Another is an expansion of its Compass data service, with anonymized patient data available now, and predictive prescriber and national-markets data available next year. (This product competes directly with a variety of services offered by IQVIA, which are currently available to pharma clients using Veeva CRM via third-party agreements; the new service is supposed to eliminate these agreements. On the other hand, Veeva and IQVIA have been engaged in legal actions against each other since 2017.) A third offering, CRM Bot, will be described later.

Over at IQVIA, the focus in recent years has been its Orchestrated Customer Experience (OCE), which enables the company’s rich data prescribers and markets to be integrated with the Salesforce platform. OCE has been upgraded recently to “OCE+”, the difference being the incorporation of a product from the company called the “Next Best recommendation engine.” “Next Best” refers to the process of identifying a preferable action to take (send a doctor an e-mail, engage with the medical science liaison, etc.) for reps or marketers to take, based on the data on hand and a set of business rules or algorithms (see chart above).

“IQVIA is uniquely positioned to bring together data, analytics, technology, and AI/ML capabilities all under one roof,” says Sanjay Chikarmane, chief product officer, IQVIA. “With OCE+, our customers can make smarter and more informed decisions through embedded intelligence that surfaces the actionable insights they need, when they need them, to better personalize the HCP experience and improve business results.”

The next-best action approach has been kicked around for several years by various IT firms and business consultants. Earlier versions had the problem of recommending self-evident actions or simply ineffective ones. But as AI tools have improved, acceptance is growing. Saby Mitra, principal, digital customer experience, at ZS Associates, has followed the evolution of the next-best concept for nearly a decade.

“Back in 2015, industry was not warming up to the idea of winning with better analytics [like next-best action]," he says. "In the 2015-2018 period, we saw basic business rules being implemented, i.e., ‘if you’re falling behind plan, do this.’ Now, these recommendations are becoming more predictive: ‘this doctor will have x patients for a therapy, and there is a high likelihood that the HCP will appreciate this relevant content on your next call.’”

Like IQVIA, ZS has a stable of data services, now combined with AI/ML tools, under the brandname Zaidyn. The company is also a high-level partner with Veeva, providing implementation services and consulting for life sciences sales and marketing teams. Mitra says that the earlier (2015-2018) instances of next-best actions generated sales bumps of 4-5%; now, with the latest range of AI/ML tools, that has nearly doubled.

One of these ZS data services, Affinity Monitor, has records on 800,000 HCPs. Within Zaidyn, use of Affinity Monitor enables marketers to analyze HCPs’ preferred channels; follow-up actions can range from looking for clinical trial candidates to assembling reimbursement information for patients. Mitra says that an evolving area of interest is accounting for the social determinants of health, itself a growing area of interest for deeper insight into patient behavior. Most recently, ZS announced a partnership with Informatica, a developer of master data-management tools, to combine Zaidyn with Informatica’s Intelligent Data Management Cloud (IDMC), creating (in the industry lingo) a “data fabric” across a range of data sources.

Veeva plans to jump more deeply into the AI game with a product called CRM Bot, which, when introduced in an expected 2025 timeframe, will employ ChatGTP resources to provide to reps not just next best actions for reps on prior call reports or channel preferences, but even to predict HCP needs by drawing patient data from Veeva Compass (a compilation of healthcare data) and Link (a compilation of HCP activity).

ChatGTP is a type of “generative AI” that, in this case, builds content or analysis based on “large language model” training. Google, Microsoft, and a host of other IT firms are racing to build comparable systems. Whereas everyday computer users have been experimenting with ChatGTP tools to create documents, songs or graphic images, even writing computer code, its use in pharma will require training on the data stored in pharma’s own repositories. Veeva notes that each pharma customer will be using its own data for training, not industry-wide databases.

The near-term objectives for tools like CRM Bot will be internal documents, such as reps obtaining an AI-generated summary of their customer lists and call plan goals. Marketing managers might use it to speed development of a marketing plan. However, there is a significant obstacle to creating documents or texts that might be sent outside the organization—even something as straightforward as an e-mail response to a physician query. All such communications depend on a prior legal and/or regulatory review. The experience of everyday computer users to date has shown that ChatGPT and related AI systems can make mistakes or create false narratives—and the consequences of that in a healthcare context could be disastrous.

“I think the jury is still out on these AI tools,” says Mitra. “The technology has clearly created excitement, but so far it hasn’t been used in a regulated industry like pharma.” He also sees it as being complementary to, and not a replacement for, AI tools like neural networks or ML. He adds that ZS has a workgroup devoted to developing this technology; eventually it and its pharma clients will find a way forward. Meanwhile, there is an intensifying debate within IT circles over creating guidelines for safe development of AI technology.

Still, there is a sense in industry that exciting new capabilities are just around the corner. “I’d like to see an application that goes beyond next-best action,” says Richardson. “For example, could reps ask for a system to tell them how to run their territory for the next three months?” He sees the value of well-qualified reps as more important than ever; but given the investment that the pharma industry makes in its field teams, there is potentially more value to be obtained.

The traditional lament of commercial operations in pharma has been overcoming the difficulties of siloed functions, both geographically (for global firms) and operationally in the duplicate efforts and lack of collaboration. IT providers have come a long way in weaving the disparate data of commercial operations into a unified “cloud” or “fabric"; the hope is the same can happen in a workforce context.

The latest IT offerings for sales force automation—including new AI tools—promise a more effective pharma sales process.

New Trends in Sales Force Organization

At its core, the pharmaceutical and life sciences industries exist to help people live healthier lives, which many might argue is the foundation for a prosperous society. COVID-19 encapsulated the intrinsic connection between these industries and the global economy; however, it also raised public awareness on what it takes to get a medicine from the manufacturer to the patient. Naturally, with such a spotlight, focus shifted toward the subject of sustainability, against the universal backdrop of looming climate emergency.

Taking into account the revenue generated by the pharma industry, as was done in a 2019 study,

 it can be deduced that the industry generates about 48.55 tons of CO2 equivalent per $1 million. This is 55% higher that the emission intensity of the automotive industry. Thus, many may not be surprised to see the recent regulatory action from governments and international institutions, be it in the form of carbon tax, tighter policies, or shipping restrictions.

With such demand for companies to meet the three pillars of the environmental, social, and governance (ESG) triad, many pharma organizations are reassessing their processes, and taking tangible actions to become more sustainable. For example, Pfizer has pledged to become carbon neutral by 2030 and 

announced a list of measures to achieve this

How temperature-controlled containers can play key role in the industry's mission for carbon neutrality across the supply chain.

Pharmaceutical Commerce - June 2023

Pharmaceutical Commerce - June 2023 Issue (PDF)

Operational Trends Surrounding the Pharma Sales Process

New Insights, Fresh Voices

The Lowdown on Logistics

IRA Journey Update

Addressing Rx Affordability

Channel Fragmentation and Diversifying Product Archetypes

Innovation in Heart Disease: A Deep Dive

New Trends in Sales Force Organization

Realistic Net-Zero Goals for Pharma

Manufacturing at the Speed of AI

Creating Value from Compliance Data