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Pharmaceutical Executive APEX Awards 

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To save time spent on manual reporting, pharmaceutical companies are turning to Natural Language Processing (NLP) which holds the combined potential for automating processes and enabling a deeper understanding of previously untapped data. 

Turning Safety and Regulatory to Business Driver with Natural Language Processing

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

WHISTLE-PF IPF Safety

PE: Given the progressive and life threatening-nature of IPF, how soon do you anticipate ENV-101 might be available to patients if the Phase IIb trial meets its objectives?

That’s going to be up to the data from the IIb trial. If it replicates what we saw in the IIa trial, that would be amazing. At that point, it’s up to the regulatory authorities, which makes it a really tough question. Obviously, as the sponsor of the trial, we're going to do everything possible to get the drug to patients as soon as possible. Since IPF is actually more deadly than most cancers, I would hope that the regulatory authorities are also keen to help us get it to patients as soon as possible.

PE: The Phase IIa trial highlighted a favorable safety profile for ENV-101. What steps are being taken in WHISTLE-PF to monitor and further validate its safety across a larger and more diverse population?

The drug was very well tolerated in the IIa trial, and also, in the additional 200 subjects that have previously been treated with the drug in oncology. So, we have a pretty robust database of 230 patients, and it's been very well tolerated in the studies. In the IPF, there were no serious adverse events, no grade three or higher events, and most of the tolerability signals were considered mild. When we go into the IIb study, we'll explore an additional two doses going even lower, which could actually be efficacious, based on what we know about those doses, and we'll have regular monitoring of all side effects, including an independent review board that looks at it as well at the end of the day.

The other difference with IIb is that we're going to allow standard of care this time, which wasn’t in the IIa trial, it was just monotherapy. At the end of the day, we'll increase the number of patients on drug. We'll have patients at lower doses, and to the patient's benefit, most of the patients will actually be on active drug in the trial.

y: The initiation of the WHISTLE PF trial for ENV-101 aligns with the company’s broader strategic goals by advancing its priority of addressing idiopathic pulmonary fibrosis (IPF) with transformative therapies. ENV-101 targets the Hedgehog signaling pathway, directly addressing the disease’s underlying pathology by reducing fibrosis and potentially reversing lung damage, distinguishing it from current IPF treatments that only slow disease progression.

Phase IIa trials have demonstrated both clinical and statistical significance in improving lung function, structure, and reducing fibrosis. With a favorable safety profile observed across 230 patients, including oncology studies, the WHISTLE PF trial will further validate these findings in a larger, more diverse population. The Phase IIb trial will explore additional lower doses to optimize efficacy and tolerability while permitting standard-of-care therapies, ensuring comprehensive data collection. Safety monitoring will include an independent review board to oversee adverse events.

The company is also collaborating with patient advocacy organizations like the Pulmonary Fibrosis Foundation (USA), PF Warriors, and international groups in Australia, Europe, and the UK. Given IPF’s life-threatening nature and the drug’s promise to outperform standard care in both efficacy and tolerability, these partnerships are important for patient education and awareness.

While regulatory timelines remain uncertain, the company is committed to expediting the process, acknowledging the severe prognosis of IPF. The potential for accelerated approval, typically rare in pulmonary conditions, underscores the drug’s unique position as a game-changer for this devastating disease.

John Hood, CEO, Endeavor BioMedicines discusses a potential timeline on availability of ENV-101 for patients with IPF and further validation of the treatment's safety profile. 

Monitoring the Safety of WHISTLE-PF in IPF Across Diverse Populations

Introduction of Panelists

e Roundtable video series, Robert Alaburda, Associate Editorial Director, talks with several experts about the building blocks for success in CAR T-cell clinical trials. The panelists introduce their expertise and background in clinical trials.

Panelists set up for addressing the clinical trial landscape, key challenges, regulations, and the future of cell and gene therapy.

The Mission Behind CAR T-cell Clinical Trials

ENV-101

PE: How does the initiation of the WHISTLE-PF trial fit into Endeavor BioMedicines’ broader strategic goals for ENV-101 and your pipeline as a whole?

Development is our highest priority. It’s really unusual in this industry to be able to work on a truly transformative drug, and that's what this one looks like. Being able to shepherd it to patients is the biggest responsibility we could have. It’s our top priority.

PE: What sets ENV-101 apart from current IPF treatments, and how does its Hedgehog signaling pathway inhibition address the disease’s underlying pathology?

To date, all approved therapies just incrementally slow the rate of decline for the disease. In contrast, 101 reverses the disease. Patients are actually getting better is an easy way to put it, which is very different than current therapies. They have improved lung function and lung structure in the terms that the lungs get bigger, and the fibrosis goes away. I think the key difference is we're going after a different target. The Hedgehog pathway is responsible for scar formation, and by blocking that, we block a key pathology associated with the disease. By blocking that pathology, we actually lead to reversal of disease in patients.

The initiation of the Whistle PF trial for ENV-101 aligns with the company’s broader strategic goals by advancing its priority of addressing idiopathic pulmonary fibrosis (IPF) with transformative therapies. ENV-101 targets the Hedgehog signaling pathway, directly addressing the disease’s underlying pathology by reducing fibrosis and potentially reversing lung damage, distinguishing it from current IPF treatments that only slow disease progression.

Phase 2a trials have demonstrated both clinical and statistical significance in improving lung function, structure, and reducing fibrosis. With a favorable safety profile observed across 230 patients, including oncology studies, the Whistle PF trial will further validate these findings in a larger, more diverse population. The Phase 2b trial will explore additional lower doses to optimize efficacy and tolerability while permitting standard-of-care therapies, ensuring comprehensive data collection. Safety monitoring will include an independent review board to oversee adverse events.

The company is also collaborating with patient advocacy organizations like the Pulmonary Fibrosis Foundation (USA), PF Warriors, and international groups in Australia, Europe, and the UK to raise awareness and facilitate trial participation. Given IPF’s life-threatening nature and the drug’s promise to outperform standard care in both efficacy and tolerability, these partnerships aim to engage more patients, ultimately expanding access to ENV-101.

John Hood, CEO, Endeavor BioMedicines discusses the key differences between ENV-101 and currently approved IPF treatments. 

The Affects of ENV-101 on IPF

Building off of the first significant surge in its history in 2023, the market for biosimilar products in the US continued to rally in 2024—taking advantage of a confluence of drivers that are changing the healthcare value equation for innovator and competing companies alike.

Notably, following the approval of nine biosimilars for AbbVie's immunology giant Humira (adalimumab) in 2023, a 10th one, branded as Simlandi, was cleared by the FDA earlier this year. The Alvotech and Teva drug was approved as the third biosimilar officially deemed as "interchangable" to Humira, which posted $14.4 billion in full-year 2023 sales. Interchangeable products may be substituted at the pharmacy level without the intervention of the healthcare provider (HCP) who prescribed the reference product.

Through early December, the FDA has greenlit 18 biosimilars in 2024. Those include six follow-on biologics for Johnson & Johnson ulcerative colitis and Crohn's disease stalwart Stelara (ustekinumab; $10.9 billion in 2023 sales), including this month's approval of Yesintek, made by Biocon Biologics; and five of Regeneron Pharmaceuricals and Bayer's eye disease big-seller Eylea (posted $9.2 billion in revenue between the two companies in 2023). In total, there are currently 63 biosimilars approved in the US, 42 of which have launched commercially.

According to a November report by Roots Analysis, the global market for follow-on biologics is valued at $24.2 billion in 2024, and will grow at a compound annual growth rate of 16.5% through 2034. Driving those numbers, of course, will be looming patent cliffs on the horizon, notably in 2028, when Merck's PD-1 powerhouse Keytruda (the top-selling drug in 2023 at $25 billion) will start coming off patent, and in 2030. In all, by the end of the decade, about $236 billion in biopharma reference product sales are at risk. This reality has attracted large innovator organizations into the world of biosimilar development in recent years, seeking a new channel to replenish the sales erosion noted. Those companies have included the likes of Novartis, Biogen, Pfizer, and Amgen (the latter two have their own marketed biosimilars to Humira—Abrilada and Amjevita, respectively).

As of Nov. 1, there were more than 80 biosimilars in development across 22 molecules, according to data from Cencora. Seventeen of those candidates are targeting indications in oncology, but biosimilar efforts are also heavily active in areas such as ophthalmology and immune disorders, as noted, and also diabetes, bone health, and growth hormones.

, Johanna DeYoung, global industry lead, healthcare and life sciences with Slalom, a business and technology consulting firm, believes the growth of biosimilars on the market, in R&D circles, and increasingly becoming accessible to a larger number of patients, has influenced the decision-making and product launch planning of innovators in two distinct ways.

"Inventor companies are now more focused on competitive pricing strategies, and being more surgical about their value propositions to maintain their market share," she says, adding that such approaches have translated to price reductions, in some cases, of originator biologics (i.e., monoclonal antibodies, insulin, erythropoietin, and anticoagulants). "For launch planning, you're seeing the impact really accelerating the need for inventor companies to innovate and bring more products to market quickly. Also investing more in that lifecycle management strategy—developing next-generation biologics or new formulations to try to continue to differentiate among the competition."

DeYoung adds that amid these dynamics, innovator companies, such as those mentioned, are more conscious of diversifying their therapeutic portfolios to include both biologicals and biosimilars in a dual approach. They are doing so via organic means or pursuing partnership and licensing arrangements with smaller developers. For innovators, carving new territories for capitalization and market share by reaching into broader segments, such as biosimilars, represents a clear example of these companies adding more dimension to their growth strategies.

While a climate advocating aggressive pricing and cost efficiency, naturally, offers opportunity and potential advantages for dedicated biosimilar makers, DeYoung notes that Big Pharma is better positioned to seize on the biosimilars uptick in the US—due to their ability to contribute robust infrastructure and market expertise.

"They have established extensive resourcing and presence in the marketplace," she says. "When we look at the development of bosimilars being quite complex and costly compared to small molecules, Big Pharma typically can afford those associated higher costs that, yes, while smaller than the reference biologic, can still range from $100 million to $300 million. The startup costs, therefore, are relatively negligible for big pharma comparatively. I think this gives them an edge in quality and reliability."

Nevertheless, even as commercial strategies shift—and proven cost savings have resulted from biosimilars in recent years (PwC predicts $43 billion in US healthcare savings by 2027)—there remain several challenges limiting their wider adoption by HCPs and use by patients. Along with the inherent manufacturing, development, and administration hurdles, newer or simmering disruptors are adding to the mix. Those include market access and reimbursement barriers created by the rebate structure between pharmacy benefit managers and manufacturers; other limited or misaligned incentives for HCPs to switch to biosimilars; the uncertain fates now, following the US presidential election, of legislation such as the Inflation Reduction Act, which includes provisions designed to encourage biosimilar uptake and formulary inclusion; and the complex legal rights arguments that remain for originator drugs.

"Purists may say that biosimilars run afoul potentially of IP protections of the reference biologics that they are building from," Meera Kanhouwa, MD, FACEP, global healthcare industry leader, Slalom, tells 

. "But the fact of the matter is the US is spending more on healthcare than any other OECD (Organization for Economic Cooperation and Development) nation and more per capita than the other top OECD nations combined. A large portion of that dollar goes to spend on pharma. So there is a need for biosimilars and biologics [together]. It may cause our traditional markets to have to shift and adapt in ways that they may not be ready for yet."

To that end, Kanhouwa notes the clear differences in the investment and resource level needed to produce biosimilars (roughly two to three years and a $100 million to develop) versus the reference biologic (maybe five to 10 years and $500 million), and without necessarily always proven differences in efficacy, which can complicate matters further.

"There's variability in terms of how that information is gathered, and with very rare exception, providers may lag a little bit as they wait to see data on the efficacy overall on the medication before prescribing it to their own patient base," explains Kanhouwa. "That's part of the natural lag [in adoption]. Plus, providers tend to be more risk-averse; they will trend toward using the medications that they are comfortable and familiar with."

Thus, the educational and transparency component around biosimilars, particularly as it applies to HCPs and patients, is critical. DeYoung reminds that biosimilar penetration still accounts for less than 30% of all biologic utilization, as HCP and patient perception is still not close to being on par with traditional generics.

"I think biosimilars need to continue to win confidence in the marketplace, which longitudinal data will help do," DeYoung tells 

. "Trust and behavior change over time. There's still opportunity to build knowledge for healthcare providers on the usage of biosimilars. There's such a burdened population, so the need for continuous improvement and process change is very real, but it's only one of the many items vying for a physician's time."

Adding to the matter is the flood of data that HCPs are burdened with today. "I heard something like if you started a practice in 1950, it took 50 years for medical information to double. Today it doubles every three months," says DeYoung. "It goes back to the connection with the HCPs and bringing them into the conversation, no matter what the pharmaceutical disruptors are."

Kanhouwa believes artificial intelligence-mediated tools and approaches can help alleviate this issue for HCPs by "enabling better information at the point of care and the point of decision-making."

Overall, one thing appears certain: For the biosimilars market to truly thrive, it may simply come down to greater transparency—into the process, the actual costs and savings, and everything in between.

Adds DeYoung: "Let's use the data in healthcare and technology to create a world where individuals and their healthcare teams can know exactly the financial and health choices out in front of them."

The biosimilars market in the US is on the rise, but barriers to greater adoption remain.

Seeking More Value, Less Cost 

Explore the latest pharmaceutical validation developments with industry experts from Barry-Wehmiller Design Group, Kneat Solutions, No deviation, and PCI. You’ll gain exclusive data-driven insights and discover emerging trends from the State of Validation 2024 industry report that are reshaping the validation landscape.


Jane Reed

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