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Pharmaceutical Executive APEX Awards 

Topic

Sales and Marketing

1rem

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Director with Simon-Kucher’s Life Sciences division

The importance of expanding your pharma sales forecasting horizon beyond the US. Learn how to effectively navigate country-specific regulatory red flags. 

Pharma Forecasting: Key Markets Investors Can’t Ignore 

AbbVie Pedro Valencia ADCs

PE: How is AbbVie using novel cancer biomarkers to develop potential first-in-class ADCs for the treatment of advanced solid tumors?

We're constantly looking for biomarkers that can help us to do two key things. The first is to tackle cancer cells. and spare normal cells. We’re looking for specific antigens that are over-expressing tumor cells, and you see limited expression in normal cells. We want to make sure that target that’s over-expressed is critical for the survival of the cancer cell. Once you block it, you can actually drive a cancer cell death. That’s what we're looking for. In that perspective, c-Met is one of those biomarkers that is over expressing multiple tumor types such as lung, colorectal, gastric, and other GA tumors. We as an industry have tried to tackle c-Met in the past but have been unsuccessful. It would actually be successful to tackle what we call met, which is a gene inside the cell.

There’s this thing called met amplification, where the cancer cell produces multiple copies of the gene, and around 30% of patients have it. We can actually tackle that with small molecules. But once the gene becomes a protein and gets over-expressed in the cell, that over-expression is something we haven’t been able to target. For example, we know that on lung cancer, c-Met over-expression is about 25% to 50% in colorectal cancer, and it could be anywhere from 30% to 70% depending how you measure it, so it’s quite prevalent.

With ADCs, we’re trying to tackle c-Met over-expression on the surface of cancer cells. That was novel, and we can do it through ADCs. 706 has a target called SEZ6, and it’s a target that is over expressed in neuroendocrine cells or neuroendocrine neoplasms. When you think about it, multiple tumor types kind of have a subset of cells that are neuroendocrine driven. Small cell lung cancer is one of the few that has everything driven by neuroendocrine cells. The beauty of SEZ6 is over-expressing those cells and limited expression in normal cells. So, we can tackle it with an ADC and drive the results that we're seeing today.

PE: ADCs have redefined the treatment of cancer in recent years. Can you please discuss the promise of this emerging class and what the future may hold?

At the end of the day, ADCs work like a trojan horse. You have a good antibody that cancer cells are happy to receive, but once you hook into the cancer cell receptor, you deliver the payload, which is pretty much chemotherapy. It’s actually a highly potent version of the regular chemotherapy cancer patients are given on a regular basis. So, from that perspective, our goal is to replace chemotherapy. Our grand goal with ADCs is to replace good old, decades old chemotherapy that is really toxic for some patients. That’s how we see the redefinition of cancer treatment in the future with ADCs. So, what do we see in the future? Well, if you think about it, chemotherapy is being given in combination with other agents. In the future, we see ADCs being given in combination with chemotherapy. There will be one with other agents such as immuno-oncology agents. So, if you combine the ADC and the PD1s, you can start seeing that synergy come together and kind of start really dreaming about cures for the patients. All in all, we're super excited about ADCs replacing chemotherapy. 

In an interview with Pharm Exec Associate Editor Don Tracy, Pedro Valencia, VP, Solid Tumor Pipeline Strategy & Execution, AbbVie, discusses using novel cancer biomarkers to develop potential first-in-class antibody drug conjugates (ADCs) and the promise that they offer. 

Utilizing Biomarkers to Develop First-in-Class Antibody Drug Conjugates to Treat Advanced Solid Tumors

US-centric forecasts are often inadequate when assessing the value of pharmaceutical drugs. In this article, we discuss the relative importance of key global pharmaceutical markets and the need to consider their unique regulatory, pricing, and market access requirements in sales forecasting.

It is easy to see why the US market commands so much attention from pharma forecasters—after all, it is the largest in the world. According to estimates from Statista and IQVIA, the US accounted for 43% of the global pharmaceutical market in 2023, followed by Europe at 19%, China at 8%, and Japan at 5%. This trend is mirrored when examining the revenue distribution of some of the largest pharmaceutical companies globally, using sales data from annual reports and SEC filings. (See Figure 1 below.)

Overreliance on US-centric forecasts risks overlooking critical factors in key markets such as Europe, Japan, and China, which collectively account for a significant portion of worldwide sales. While US sales projections often form the backbone of global forecasts, extrapolating these figures without accounting for the unique characteristics of other markets introduces significant risks and errors.

WHY US-CENTRIC PHARMA FORECASTS CAN FALL SHORT

While the US remains the largest market, it represents less than half of global pharmaceutical sales. The 80:20 rule suggests that to enhance forecast accuracy, it is essential to consider a few additional, large markets—specifically Germany (as the largest European market from which extrapolation to the rest of Europe is reasonable), China, and Japan—while maintaining a practical scope for sales forecasting efforts.

Healthcare markets outside the US differ markedly. In the US, drug prices are predominantly set freely, despite recent legislation, such as the Inflation Reduction Act, allowing the government to negotiate a limited set of drug prices under government plans. In contrast, Europe, Japan, and China are governed by strict health technology assessment-like government authorities that control price and market access, leading to significant disparities. For example, a study by the US Department of Health and Human Services found that drug prices across 32 countries varied by a factor of 1.7 to 7.8 compared to US prices. This analysis likely underestimates the differences, as it does not include China—a key global market known for significantly lower prices than Western countries. Moreover, the regulatory landscapes in these regions differ considerably from that of the US. While price discrepancies are widely acknowledged within the industry, the impact of differing regulatory decisions is often underestimated.

NAVIGATING REGULATORY NUANCES IN JAPAN AND CHINA

The likelihood of achieving marketing authorization can vary significantly between the West and markets such as China and Japan, with important implications for sales forecasts. To estimate the probability of regulatory approval, analysts typically rely on technical benchmarks such as the availability of surrogate markers, historical success rates in the target indication, and scientific expert opinions on the target drug’s risk/benefit ratio. However, these considerations often focus primarily on the US and Europe, neglecting region-specific factors outside the West.

One critical aspect often overlooked is ethnic patient representation or inclusion of local trial sites in pivotal clinical trials, which is essential for regulatory approval in China and Japan. Local data on ethnic Chinese and Japanese populations is generally required, even for (ultra)orphan indications where conducting large, international trials may be challenging. This requirement can significantly impact the likelihood of achieving marketing authorization and, by extension, the accuracy of sales forecasts.

For instance, gene therapies targeting orphan indications have struggled to gain approval in China and Japan. Currently, none have been approved in China, and only three from a total of 17 are approved in Japan. In China, 16 out of 17 of the pivotal clinical trials did not include trial sites in mainland China, which can help rationalize why none of the drugs are approved yet. A case in point is Novartis’ Zolgensma, which received clearance from the Chinese Center for Drug Evaluation to run an additional Phase III trial for the drug in China, highlighting the requirement for local Chinese data rather than relying solely on international data. The only exception so far is Elevidys, which included Chinese patients in its pivotal clinical trial package; it is expected that a regulatory filing in China may occur in the future, as the drug only received conditional approval in the US last year and has not yet been approved by the European Medicines Agency.

Similarly, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) has stringent requirements regarding ethnic patient representation. There are only three gene therapies currently approved in Japan: one from a Japanese company and two from Novartis, namely Zolgensma and Luxturna. For both of these treatments, there was significant scrutiny, as the evidence package included only a few Japanese patients. In fact, the PMDA mandated the collection of additional data post-approval, citing the very low numbers of Japanese subjects for both products. Further highlighting the necessity for local data, three gene therapy manufacturers are currently running additional standalone Phase III trials in Japan, in addition to their existing international studies—specifically for Adstiladrin, Hemgenix, and Roctavian.

These examples illustrate how country-specific regulatory factors can significantly affect the accuracy of sales forecasts, especially given the substantial contribution of markets such as China, Japan, and Europe to the overall value potential of pharmaceutical drugs. While it is common practice to base global projections on US sales forecasts, relying solely on historical averages of price and volume differences across countries may fail to capture the complexities of ex-US markets. Overlooking nuances in regulatory requirements and pricing and market access conditions unique to each region can lead to significant sales forecasting errors. Notably, ongoing regulatory reforms in Japan, aimed at streamlining approvals, could further shift market dynamics and should be closely monitored by investors.

Given this landscape, we suggest three underlying strategies or messages in particular.

 Limiting forecasts to the US can lead to significant errors; incorporating key markets such as Germany, Japan, and China helps capture a broader range of regulatory, pricing, and access challenges that directly impact valuation models.

Regulatory approval hinges not just on efficacy data but also on ethnic representation and local clinical trial involvement. These factors are crucial and can be dealbreakers for approval, affecting market timelines and sales forecasts.

Pricing and market access challenges are highly variable:

 Unlike the relatively free pricing model of the US, strict payer controls in Europe, Japan, and China result in significant pricing and access disparities that can alter expected revenue projections. Understanding these market-specific barriers is critical for accurate forecasts.

As the pharma terrain continues to evolve, staying ahead of these regulatory and market dynamics will be crucial for forecasters and investors alike. The future of pharma is global—are your forecasts ready to reflect that.

Na Wie, Partner; Joerg Tritschler, Partner; Martin Slusarczyk, PhD, Director; All with Simon-Kucher’s Life Sciences division

This study demonstrates high-throughput analysis of BTEX compounds from several matrices (air, water and soil). Detection limits in the single-digit part-per-billion concentration range (by volume) are readily achievable within seconds using SIFT-MS because sample analysis is achieved without chromatography, pre-concentration, or drying. We also present a calibration approach that enables speciation of ethylbenzene from the xylenes in real-time.


High-Throughput Analysis of Volatile Compounds in Air, Water, and Soil Using SIFT-MS

This application note summarizes key SIFT-MS results presented in a peer reviewed article entitled “Unreported VOC Emissions from Road Transport Including from Electric Vehicles.” Learn how the Wolfson Atmospheric Chemistry Laboratory at the University of York used SIFT-MS for VOC analysis in its platform to experimentally verify that motor vehicle screen wash is a significant unreported source of VOC emissions (especially for ethanol and methanol). 


Real-Time Roadside Monitoring of Unreported VOC Emissions from Road Transport by SIFT-MS

Real-Time Measurement of EPA Regulated HON Compounds and Environmental Pollutants Using SIFT-MS

Data from the CIBMTR trial demonstrated that Kite’s Yescarta (axicabtagene ciloleucel) produced high overall survival (OS), objective response rate (ORR), complete response (CR), and effectiveness consistent with pivotal trial outcomes in treating patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). According to the company, the analysis included real-world evidence (RWE) from the largest analysis of second-line treatment with Yescarta in 2022-2023 based on Center for International Blood and Marrow Transplant Research (CIBMTR) registry data.

“We are pleased that Yescarta’s overall survival benefit for patients with early relapsed/refractory large B-cell lymphoma is confirmed in the largest real-world analysis of a broader patient population,” said Dominique Tonelli, VP, global head, medical affairs, Kite, in a press release. “By studying outcomes in the real world, we consistently demonstrate that patients treated with Yescarta have the opportunity to live longer.”

In abstract #526, 446 patients from 89 centers in the United States from the CIBMTR registry who received second-line Yescarta treatment showed outcomes consistent with the ZUMA-7 trial, with a demonstrated ORR of 79% with a CR rate of 64%. Additionally, the one-year rate of duration of response was 66%, progression-free survival (PFS) rate was 53%, event-free survival was 53%, and OS was 71%.

“It is reassuring that the largest real-world dataset for axi-cel as a second-line treatment for relapsed/refractory large B-cell lymphoma, across a broader patient population than the ZUMA-7 pivotal study or Phase II ALYCANTE study for transplant-ineligible patients, has demonstrated consistent outcomes at 12-months median follow-up as in ZUMA-7,” said lead investigator Caroline Lee, fellow, hematology medical oncology, Stanford Medicine, in the press release. “These data should provide further confidence to physicians that earlier use of [Yescarta] can provide the best chance for overall survival and possibly a cure for these patients.”

In abstract #527, RWD from 615 patients with R/R LBCL from 109 centers from the CIBMTR registry demonstrated a decreasing trend in incidence, severity, and duration of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome following treatment with Yescarta in the third-line setting. Additionally, these patients had significantly lower incidences of Grade ≥ 3 CRS compared to those treated during 2017–2019. Further, patients treated in the later time periods of 2022-2023 and 2020-2021 experienced significantly shorter duration of CRS compared to 2017-2019.

Lastly, in abstract #4505, findings from the Phase II ALYCANTE study in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy and autologous stem cell transplantation found that after a short initial deterioration at one month post-infusion, patients reported longer-term stability or improved quality of life across multiple parameters, after up to a year of follow-up. Results found that 61 patients reported a lower symptomatic level at three months compared to baseline. After three months, 45% of patients presented a stable global health condition and 73% stable physical functioning. After a year, most patients reported a more stable condition, with clinically and statistically significant improvement.

“ALYCANTE is the first study to assess [Yescarta] as second-line therapy in transplant-ineligible relapsed/refractory large B-cell lymphoma patients, with previous study findings confirming its efficacy in this patient population,” said Roch Houot, head, hematology department, University Hospital of Rennes, France, coordinator, ALYCANTE study, in the press release. “This current study shows that, in this frail and elderly population, [Yescarta] not only increased the quantity of life but also improved the quality of life which was comparable to that of the transplant-eligible patients, and allowed recovery of a fatigue score close to the general French population.”

1. Kite Presents New Data Underscoring Curative Potential of Yescarta® in Relapsed/Refractory Large B-cell Lymphoma at ASH. 

December 8, 2024. Accessed December 9, 2024. https://www.gilead.com/news/news-details/2024/kite-presents-new-data-underscoring-curative-potential-of-yescarta-in-relapsedrefractory-large-b-cell-lymphoma-at-ash 

Real-world evidence from the largest analysis of second-line treatment with Yescarta in 2022-2023 demonstrated a high overall survival rate in patients with relapsed/refractory large b-cell lymphoma. 

Martin Slusarczyk, PhD

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