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To get their messages out in this age of polarisation and "too much information", marketers need to shout louder, have a more dramatic point of view and gather a league of similar advocates to succeed. Al Topin sees the solution in common sense and courage.

Survival/Success in the Age of Too Much Information

What many in our industry may overlook as they try to identify some new trend are the changes that move below our feet. And they have the potential to disrupt even the most thoughtful marketing plans, writes Al Topin.

Feel the Earth Move Under Your Brand?

The “seven significants” for brand planning in 2016 that pose the best chance for stable footing amid the seismic state of today’s ever-changing healthcare landscape.

Do I have the only e-mail inbox clogged with more and more content about content marketing?

Some Content on Content Marketing

Digital devices have made it possible to conduct business without ever leaving your desk. But something is just plain old wrong with that, writes Al Topin.

In the Digital Age, Don't Forget to G.O.Y.A

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

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.

FDA Challenges to Broad Label Laws for PD-1 Inhibitors

PD-1 restrictions

PE: Can you explain the FDA’s reasoning behind targeting the broad labeling of PD-1 inhibitors and how this might impact future drug approvals in oncology?

I think the change in labeling is going to push both providers and patients to file challenges, because, again, that access to treatment, I think it's already opened the door to product liability issues. I have a quote from the FDA that says ‘If patients with low or no PD-1 expressions are not expected to benefit based on the available data, then administering anti-PD1 therapy has the potential for harm, including serious immune related adverse events on top of a maladency that could markedly affect a patient's quality of life.’ After looking at that, I think either way, manufacturers and insurance companies are going to be sued on access either to the treatment because the narrow language to label or because of possible adverse effects allowed under a broader label.

Ron Lanton, Partner, Lanton Law, discusses why the regulatory body made the decision to place restrictions on PD-1 inhibitors for gastric cancers. 

Rationale Behind the Recent FDA PD-1 Inhibitor Label Restrictions

Legal Action PD-1 Inhibitor

PE: What legal defenses or strategies might companies consider arguing in favor of keeping broader indications for their PD-1 inhibitors in gastric cancers?

I think that many providers have said that limiting the use of PD-1 inhibitors in gastric cancer is not going to help anybody. I think that one legal defense that could be used is that biomarkers limit access, maybe based on a genetic discrimination claim, which I haven’t seen in a couple of years. That’s kind of died off from what I’ve seen. It’s still there, but it’s not in the news the way it used to be. But to continue on this thought, I think the use of biomarkers is key in clinical studies. I think that a lot of people are afraid that using them in such a strict manner is going to undermine a lot of the clinical studies and limit access for patients who have been accepted under the Right to Try laws. It’s a volatile topic, but it’s definitely going to come back to the forefront with something like this.

Ron Lanton, Partner, Lanton Law, discusses potential challenges that will come as a result of the FDA’s recent move to tighten label restrictions on PD-1 inhibitors for gastric cancers. 

Al Topin

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