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John Pagliuca is Vice President for Business Development at SCIO Health Analytics.

Consumers of life sciences products are reluctant customers, and this reluctance can turn into non-compliance. Organizations and providers need to understand patients at a human level, and what will motivate them to stay with a treatment plan, writes John Pagliuca.

The Reluctant Customer: Using Personas to Improve Compliance

There is a tremendous, untapped market of undiagnosed patients for a variety of conditions, writes John Pagliuca. But how do you identify them when they are essentially hidden from view through conventional means?

Seizing the Undiagnosed Patients Market Opportunity

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

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. 

Yescarta Demonstrates Promise in Treating Relapsed/Refractory Large B-Cell Lymphoma 

Peer Exchange: Technology's Role in Achieving Greater DE&I in Clinical Trials

In this roundtable discussion, industry experts gathered to address the state of achieving greater diversity in clinical research. The group highlighted a variety of topics including current challenges they are seeing, the use of technology, and more.

Out-of-Pocket Costs for MS Medications Rise While They Drop for Other Neurologic Conditions

The out-of-pocket cost for MS disease-modifying therapies jump by 217% going from $750 per year in 2012 to $2,378 per year in 2021.

OpenAI Adds $200 Monthly ChatGPT Pro Subscription With New Model

OpenAI is introducing a higher-priced paid tier for its chatbot ChatGPT that includes unlimited access to its most powerful artificial intelligence models, including an improved version of its software that can perform human-like reasoning tasks.

The new ChatGPT Pro option, announced in a livestreamed event on Thursday, will cost $200 a month and offer access to an expanded version of o1, its reasoning model. OpenAI previously introduced a preview of the model in September, but the company said the new version is faster and better at solving competitive math and code problems.

Cencora Launches Accelerate Pharmacy Solutions to Enhance Support for Hospital and Health System Customers

Cencora announced the launch of Accelerate Pharmacy Solutions, a unified portfolio of solutions designed to help hospital and health systems customers optimize operations and improve financial performance.

Accelerate Pharmacy Solutions brings together Cencora’s suite of pharmacy and supply chain solutions, enabling Cencora to deliver an enhanced customer experience and integrated support to address customers’ evolving needs. The solutions range from specialty drug purchasing and cost management strategies to logistics, transport, supply chain and inventory management solutions.

Don't miss part 4 of my interview with AllazoHealth's William Grambley!

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The latest news for pharma industry insiders.

Pharma Pulse 12/9/24: Technology's Role in Achieving Greater DE&I, Out-of-Pocket MS Med Costs Rise, Others Drop & more

SPIMA Launch

PE: SPIMA was funded with a strong academic foundation and support from multiple institutions. What can you tell us about these collaborative partnerships and how they help develop SPIMA’s pipeline?

SPIMA was born thanks to collaboration between two prominent institutions in the University of Montpellier in France. The first is IBMM, which specializes in the chemistry of peptides, and the second is IRMB, which specializes in the pharmacology of inflammation. Basically, scientists at IBMM designed the initial lead drug candidates, which are stable peptide, and then the scientist at IRMB were able to test them in vitro and in vivo.

They worked together for several years, and they brought the lead candidate to the pre-clinical phase through a global patent. At one point, the technology transfer office at the University of Montpellier felt that it was time to create a spinoff company in order to bring it to a clinical phase, and this is where I joined the team. We are continuing to collaborate with the technology transfer office and with the joint scientific institutions in order to progress our lead drug candidate.

Spima was founded through a collaborative effort between two academic institutions in southern France: IBMM, specializing in peptide chemistry, and IRMB, focusing on inflammation pharmacology. This partnership enabled the design of stable peptide drug candidates by IBMM and their in vitro and in vivo testing by IRMB, leading to the preclinical development and patenting of the lead candidate. The University of Montpellier's Technology Transfer Office facilitated the creation of Spima to advance these discoveries into clinical development.

Spima focuses on peptide-based immunotherapies due to their unique ability to target intracellular protein-protein interactions. Unlike small molecules, which lack specificity, or large molecules, such as antibodies, which cannot penetrate cells, peptides occupy a middle ground. Spima’s stable peptides demonstrate both cell permeability and specificity, making them ideal for addressing these challenging targets.

The company prioritizes indications with high unmet medical needs. Acute pancreatitis, with over 130,000 annual U.S. cases but no FDA-approved treatments, is a key focus. Other targets include scleroderma, a severe autoimmune disease, and cancers such as diffuse large B-cell lymphoma with MYD88 mutations, where Spima’s drug candidates have shown promising potential.

From a regulatory perspective, Spima anticipates minimal hurdles, as peptides are well-established in drug development, akin to small molecules. Recent approvals of peptide-based therapies for conditions like obesity further reinforce this outlook.

Spima emphasizes patient-centric design, guided by one of its co-founders, a physician specializing in inflammatory diseases. The company aims to integrate patient and physician insights from the earliest stages of drug design and expand these collaborations through clinical trials and advisory boards, ensuring that patient needs remain central to therapeutic development.

Mohamed Haitham Ayad, CEO, co-founder, SPIMA Therapeutics, discusses the company’s launch and how multiple institutions have supported its pipeline. 

The Launch of SPIMA Therapeutics

Future Studies

PE: How might this labeling challenge influence future drug development strategies, especially in terms of targeting specific cancer subtypes or biomarkers in gastric cancers?

I think it’s going to slow down R&D altogether, that’s the first thing. I think these restrictions that were noted by scores that were cut off below a 10. I think Merck says something about that's going to exclude about 65% of new patients with HER2-negative stomach cancer. Additionally, this is going to also make it so that the drug is more expensive than it already is, and that's definitely going to affect future access to insurance formularies that are going to restrict access. I know we've talked before about DVMs and how they view price and how all that comes, to how they think about things and what they put on their formulary. So, this is definitely going to be an external factor to that.

 The FDA’s recent challenges to the broad labeling of PD-1 inhibitors for gastric cancers, particularly around PD-L1 expression, could have far-reaching legal, regulatory, and strategic implications for pharmaceutical companies and healthcare providers. This shift could significantly restrict patient access to these treatments by mandating a threshold for PD-L1 expression, which is anticipated to exclude a large portion of patients, particularly those with low PD-L1 expression levels. These patients, lacking alternative treatment options, may initiate litigation, claiming denial of necessary treatment.

From a regulatory standpoint, companies will need to revise labeling to specify PD-L1 thresholds, impacting compliance procedures and possibly requiring additional studies. This narrowing of indications is also likely to increase the cost of these therapies, potentially limiting their inclusion in insurance formularies and intensifying market access challenges. Consequently, insurers might also face legal scrutiny from patients and providers who feel that access is unfairly limited due to the new labeling standards. Moreover, product liability claims could arise if adverse events occur under a broader indication, adding further risk.

Pharmaceutical companies may argue that biomarkers can restrict access, which could touch on genetic discrimination concerns, though the Genetic Information Nondiscrimination Act (GINA) may limit this defense’s applicability. This labeling challenge could also impact future drug development strategies, as companies may become more cautious about targeting treatments based on specific biomarkers. The FDA’s stance may deter innovation by slowing research and development (R&D) timelines, as companies may hesitate to invest in drugs with narrow patient populations. This situation may also rekindle debate around Right to Try laws, which aim to broaden treatment access for critically ill patients. Overall, the FDA’s challenge is poised to reshape market dynamics and legal risks, creating a complex landscape for manufacturers and healthcare providers alike.

Ron Lanton, Partner, Lanton Law, discusses ways that the recent FDA PD-1 inhibitor label restrictions could influence future drug development strategies.  

The Influence of PD-1 Inhibitor Label Restrictions on Future Studies

FDA PD-1 Inhibitor Challenge

PE: What are the legal implications of the FDA challenging the broad labeling of PD-1 inhibitors for gastric cancers?

It's definitely going to limit the number of patients who qualify for the treatment. I think because of this limiting factor, it's going to open up the industry to lawsuits. I think the lawsuits are going to likely be from patients or providers who believe that they're being denied access to necessary treatment based on these new, more restrictive labeling criteria that we're seeing.

PE: How does this FDA action affect pharmaceutical companies from a regulatory and compliance standpoint?

What that means is that only patients with a certain level of PDL-1 expression would be able to be eligible for the treatment for these inhibitors in gastric cancer. Again, I think when you look at the whole aspect of what this means, it's going to mean excluding a large portion of patients from the treatment.

The FDA’s recent challenges to the broad labeling of PD-1 inhibitors for gastric cancers, particularly around PD-L1 expression, could have far-reaching legal, regulatory, and strategic implications for pharmaceutical companies and healthcare providers. This shift could significantly restrict patient access to these treatments by mandating a threshold for PD-L1 expression, which is anticipated to exclude a large portion of patients, particularly those with low PD-L1 expression levels. These patients, lacking alternative treatment options, may initiate litigation, claiming denial of necessary treatment.

Ron Lanton, Partner, Lanton Law, discusses the legal implications of the FDA’s broad label challenge to PD-1 inhibitors for gastric cancers.

John Pagliuca

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