The reasoning for this situation is complex and multifactorial some of the causes are related to the following:

Lack of awareness of the new biomarker/test

Lack of proper training/optimization in running the test in the lab

Laboratories considering the adoption of a new biomarker test must assess its clinical utility, cost-effectiveness, and impact on patient care in comparison to existing diagnostic methods.

Additionally, they may need to provide training for laboratory staff and ensure seamless integration of the test into current laboratory information systems.

Developing a validated companion diagnostic (CDx) test aimed at identifying suitable patients for precision medicine (PM) treatment does not automatically guarantee precise detection of the appropriate patient population and subsequent delivery of treatment. In the current landscape of clinical diagnostic testing, many patients do not receive necessary tests in a timely manner, despite their availability.

Even after obtaining regulatory approval and completing technical optimization, the commercial availability of a biomarker test does not guarantee immediate uptake in laboratories. Factors such as reimbursement policies, clinician awareness and acceptance, and the availability of supporting infrastructure and resources can influence the pace of adoption.

This delay in accessing tests, and consequently treatments, is attributed to the inadequacies of the current clinical diagnostic testing landscape. This unprepared environment poses numerous challenges to the clinical implementation of CDx tests, hindering their diffusion and utilization.

To delve deeper into how data-driven engagement can address these challenges and facilitate the adoption of new biomarker tests, we invite you to join our upcoming webinar on November 13th from 1-2 PM EST: 

Optimize Your Physician Engagement Strategy: Data-Driven HCP Education in Precision Medicine

This session will focus on effective strategies for leveraging data and omnichannel approaches to enhance physician engagement and lab education. By rapidly identifying and educating healthcare professionals about your precision medicine therapies, we can ensure timely awareness and understanding, ultimately driving adoption rates and improving patient access to essential testing and treatment


Register here 

The uptake of a new biomarker test takes too long.

This delay in accessing tests, and consequently treatments, can be attributed to the unpreparedness of the clinical diagnostic testing landscape into which these tests are introduced. Such a setting presents numerous challenges to the widespread implementation of CDx tests, hindering their diffusion and adoption.

Awareness among physicians regarding biomarker tests is crucial, as they initiate the testing process by ordering these tests. The slow uptake of tests that follows is often due to a lack of awareness regarding the clinical utility of new biomarkers and associated therapies.

The availability of testing is paramount for adoption, but equally important is the availability of tests in laboratories that physicians trust and prefer. Hence, raising awareness among laboratories is crucial for facilitating the offering of tests.

By investing in pre-launch planning and CDx tests, the clinical diagnostic testing landscape can be positively impacted. Strategic preparation ensures that early adopters are informed about 'how and where to request testing' and understand how to interpret the results. This, in turn, benefits biopharmaceutical companies by increasing the return on investment (ROI) through improved access to testing and treatment for more patients.

To explore more about how data-driven physician engagement can enhance the adoption of precision medicine, join our latest webinar, 

‘Cutting Through the Noise: Data-Driven Physician Engagement in Precision Medicine’ on November 13th, 1-2 pm EST.

Join Gosia Leitch, VP of Engagement Solutions at Diaceutics to explore how data driven omnichannel strategies can enhance engagement by precisely targeting physicians treating patients with relevant biomarkers. Discover how leveraging laboratory data can accelerate the adoption of novel treatments, enabling rapid engagement with physicians within 24 hours after a patient tests positive for a relevant biomarker.

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In the field of oncology alone, inefficiencies stemming from inadequate market development planning for companion diagnostic (CDx) tests currently result in 50% of patients not receiving appropriate testing for biomarker-guided treatment.

ALK was first discovered in 1994, originally identified as a fusion gene in ALCL where it was found to drive oncogenesis via constitutive kinase activity through a chromosomal rearrangement known as ALK fusion. This breakthrough highlighted how specific genetic alterations could underpin certain cancers, laying the groundwork for targeted therapies and opening the doors to understanding the role of ALK in other malignancies, including inflammatory myofibroblastic tumors and NSCLC. The identification of ALK rearrangements in 2007, where the ALK gene fuses with other genes such as EML4 in lung cancer, was a pivotal moment in the understanding of oncogenic drivers leading to the development of ALK inhibitors - a transformational treatment for patients with ALK-positive cancers.



ALK-positive lung cancer: A game-changer in NSCLC treatment

The most notable impact of ALK's discovery has been in NSCLC, where ALK rearrangements are present in approximately 3-7% of patients. These patients tend to be younger, with little or no smoking history.

In 2011, the U.S. FDA approved crizotinib, the first ALK inhibitor, as a targeted therapy for ALK-positive NSCLC. Crizotinib dramatically improved progression-free survival (PFS) in patients by specifically targeting the ALK fusion protein and halting the growth of cancer cells. Since then, more advanced ALK inhibitors, such as alectinib, brigatinib, and lorlatinib, have been developed to overcome resistance and improve patient outcomes. These therapies have shown remarkable efficacy in extending PFS and overall survival (OS) in patients with ALK-positive NSCLC.



The evolution of ALK-positive NSCLC therapies

Patients with ALK-positive NSCLC who initially benefited from crizotinib often experienced disease progression due to acquired resistance. This challenge spurred the development of second- and third-generation ALK inhibitors.

, approved by the FDA in 2017, demonstrated superior efficacy in preventing brain metastases and improved overall survival compared to crizotinib. A study, presented at the European Society of Medical Oncology Congress in 2023, highlighted the efficacy of alectinib in early-stage NSCLC. Patients treated with alectinib showed a 76% reduction in the risk of disease recurrence or death compared to those receiving platinum-based chemotherapy, the non-personalized therapeutic alternative.

, a third-generation ALK inhibitor, has been crucial for patients whose disease progressed on earlier therapies. Its ability to cross the blood-brain barrier has made it particularly effective in treating brain metastases, a key cause of mortality in ALK-positive NSCLC patients.


ALK beyond lung cancer: Expanding its role in precision medicine 

Whilst ALK is most closely associated with NSCLC, its role as a biomarker has expanded across multiple cancer types. ALK rearrangements are now recognized in several cancers, allowing for the application of ALK inhibitors in additional indications.

 ALK was first discovered in ALCL, and targeting ALK rearrangements in this rare lymphoma has been transformative. Brentuximab vedotin, in combination with ALK inhibitors like crizotinib, has shown significant improvement in outcomes for ALK-positive ALCL patients.

 ALK mutations also play a role in neuroblastoma, a pediatric cancer. ceritinib, another ALK inhibitor, has shown promise in treating ALK-positive neuroblastoma, offering new hope to young patients with this aggressive disease.

Inflammatory Myofibroblastic Tumors (IMT):

 ALK rearrangements are also seen in these rare soft tissue sarcomas, allowing for targeted therapy with ALK inhibitors. These tumors, previously difficult to treat, have shown improved outcomes with the introduction of precision medicine approaches.

The Broader Impact of ALK in Precision Medicine

The success of ALK-targeted therapies has underscored the importance of biomarker-driven treatment approaches in precision medicine. ALK's journey from discovery to a frontline cancer therapy demonstrates how understanding the genetic makeup of a patients tumor can lead to tailored treatments that improve outcomes and quality of life. 

With each new generation of ALK inhibitors, patients are living longer, healthier lives. The ability to identify patients with ALK rearrangements early, through comprehensive diagnostic testing, has become critical in ensuring the timely delivery of these therapies. Diaceutics has long championed the role of diagnostic testing in precision medicine, ensuring that the right tests are available to identify patients, enabling timely access to these innovative therapies.


As we celebrate 30 years of ALK’s discovery, the future of ALK targeting therapy continues to look promising. Ongoing research into the mechanisms of resistance, along with the development of more potent and brain-penetrant ALK inhibitors, ensures that this biomarker will continue to improve patient outcomes in the coming decades.

Furthermore, ALK serves as a model for the broader field of biomarker-driven oncology. Its success highlights the critical role that precision medicine plays in transforming how we treat cancer—shifting from a one-size-fits-all approach to one that is tailored to the individual patient’s genetic profile.

As a leader in precision medicine, Diaceutics remains at the forefront of enabling access to these targeted therapies. Our extensive real-world datasets and deep understanding of diagnostic pathways enables our pharma partners to continuously identify the right patients, enabling them to receive the right treatment at the right time to positively benefit their disease outcome.



Here’s to 30 years of innovation, and to the next 30 years of breakthroughs in ALK-targeted therapy and precision medicine.

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2024 marks the 30th anniversary of the discovery of Anaplastic Lymphoma Kinase (ALK) as a biomarker, a milestone that has significantly shaped the landscape of precision medicine. Initially identified in 1994 in anaplastic large cell lymphoma (ALCL), ALK has evolved from an intriguing oncogene into a critical therapeutic target, revolutionizing the way we approach various cancers, particularly non-small cell lung cancer (NSCLC). Over the past three decades, ALK-targeted therapies have demonstrated remarkable success, offering a lifeline to patients who might otherwise have limited treatment options. As we reflect on three decades of advancements, we explore the journey of ALK from its discovery to its current applications in targeted therapies, highlighting real-world case studies that underscore its impact.

New data have been presented for Trastuzumab-deruxtecan (T-DxT, Enhertu) already approved for HER2-positive breast cancer. The DESTINY-Breast12 study demonstrated durable intercranial activity in patients with brain metastases (Abstract LBA18). However, pathological assessment of HER2-low levels in order to select patients for T-DxT treatment remains a challenge. The DESTINY-Breast06 study examined the concordance of HER2 assessment between local and central labs and reported it to be approximately 78%. Out of 349 patients scored as HER2 null locally, 64% were found to be HER2-low or HER2-ultralow by central testing (Abstract LBA21). These results underscore the urgency to improve biomarker testing in order to select all eligible patients for T-DxT treatment.

Claudin-targeted antibody–drug conjugates (ADCs)seem to be a promising emerging treatment option for solid tumors. Two ADCs targeting claudin 18.2 (SHR-A1904, Abstract 609O and XNW27011, Abstract 651P)demonstrated manageable safety profiles and promising efficacy results in early trials in gastric, gastroesophageal and gastrointestinal tumors. Treatment with claudin-6 targeting (CLDN-6) ADC DS-9606ademonstrated manageable and tolerable safety in solid tumors (Abstract 610O).Encouraging early results have also been reported for TORL-1-23 targeting CLDN-6in solid tumors (Abstract 721MO).Although an unselected patient population was enrolled in the phase I study, CLDN-6 positive ovarian patients in particular responded well to treatment with an objective response rate (ORR) of 50% compared to 26% in overall population. The Phase II trial will include CLDN-6 positive patients, emphasizing the importance of biomarker testing and selecting the right patient for the right treatment. 

PRMT5 is an emerging target in patients with MTAP deletion. An early-phase trial with AMG-193 has shown acceptable safety profiles and promising anti-tumor activity across different solid tumors, with an ORR of 11.8%, 8.7% and 10.5% in patients with non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma and biliary tract cancer respectively (Abstract 604O).

Precision oncology is making advancements across different indications, with biomarker testing as an integral part of patient care. To name a few:

Results from the phase II INSPIRE study demonstrated promising efficacy of nivolumab with ipilimumab (Opdivo-Yervoy)combination treatment in deficient mismatch repair (dMMR) prostate cancer (Abstract 642TiP).

A new PD-L1-directed ADC, SGN-PDL1V, showed encouraging early data in NSCLC and HNSCC PD-L1-positive tumors (Abstract 607O).

KRAS G12Cremains target of interest. Data from theKRYSTAL-12 trial reconfirmed adagrasib (Krazati) as an efficacious treatment option for KRAS-mutated NSCLC patients and suggested intracranial efficacy inpatients with brain metastases (although patient numbers were low)(Abstract LBA57). 

Sotorasib (Lumakras), already approved for NSCLC, is showing efficacy in other indications as well. In combination with anti-EGFR monoclonal antibody panitumumab (Vectibix) and chemo in first-line KRAS G12C-mutant metastatic colorectal cancer showed high response rate (tumor shrinkage in more than 75% of patients) according to data from the phase I Code BreaK 101 study (Abstract 505O). 

The KEYNOTE-811 trial demonstrated improved overall survival (OS) with first-line pembrolizumab in combination with trastuzumab and chemo vs. placebo (20months vs.16.8 months) in patients with treatment-naive unresectable, HER2-positive metastatic gastric/gastro-esophageal junction carcinoma (Abstract 1400O). 

Promising efficacy results were displayed from early-phase studies for new tyrosine kinase inhibitors (TKIs) in ALK-positive (NVL-655, ALKOVE study, Abstract 1253O)and ROS1-positive (NVL-520, ARROS-1 study, Abstract 1256MO) NSCLC, which could be potential future therapeutic options for the patients who developed resistance to previous lines of treatment.

ASP3082, a KRAS G12D selective protein degrader, demonstrated an acceptable safety profile, and the promising ORR of 23% in NSCLC and 18.5% in pancreatic KRAS G12D mutated cancers (Abstract 608O).

A tumor-agnostic approach seems to be the way to move forward. This was supported by results from the ROME trial(Abstract LBA7), a randomized, multi-basket phase II study where 400 pre-treated patients with advanced or metastatic solid tumors across different indications with detected actionable genetic alterations were treated with different targeted treatments or immune checkpoint inhibitors, ultimately reporting a significantly improved ORR (17.0% versus 9.5%, p=0.027) and median progression-free survival (PFS; 3.7 months vs. 2.8 months, p<0.0001) vs. standard-of-care. The role of a molecular tumor board was critical for the assessment of detected genetic alterations and treatment selection. In an effort to support future tumor-agnostic trials, ESMO created the Tumor-Agnostic Classifier and Screener (ETAC-S) tool, providing minimal requirements for assessing and defining the tumor-agnostic potential of molecularly guided treatment options.

Artificial intelligence (AI) is becoming an integral part of precision oncology and medical care, although clinical validation and regulatory requirements remain challenging for AI-driven medical devices. GigaPath has been discussed at the ESMO presidential symposium as a promising new AI tool for digital pathology, with improved mutation prediction and cancer subtyping that can be utilized for clinical diagnostics and to support decision making (Abstract 1942O,Xu et al, Nature, 2024). Moreover, the AI-driven genomic test TNBC-DX demonstrated potential in a retrospective validation study, enabling identification of early-stage, triple-negative breast cancer patients likely to benefit from neoadjuvant taxane-carboplatin chemotherapy (Abstract 237MO).In order to support further progress in the field, ESMO is organizing its first AI and Digital Oncology congress in 2025.

Liquid biopsy testing and ctDNA detection are being extensively studied across different cancer types, especially in early-stage disease, for risk stratification and minimal residual disease (MRD)detection, as well as for guiding treatment decisions. Using Natera’s Signatera assay, the interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated that ctDNA-based MRD detection can accurately predict risk of recurrence and potential benefit from adjuvant chemotherapy in resectable colorectal cancer (Abstract 553P, 554P, 555P, 558P, Nakamura et al, Nat. Med., 2024). The predictive value of ctDNA has also been demonstrated in early-stage lung cancer (Abstract 1226P; IMpower010 study, Abstract 1211P;ctDNA-Lung-Detect trial, Abstract 1236P). However, test sensitivity and high false negative rates remain suboptimal, and improvements are urgently needed. In an effort to bypass this obstacle, a group from Stanford university is developing PhaseED-Seq, personalized cancer profiling by deep sequencing, and presented impressive data on improved limit of detection and sensitivity they were able to achieve with this approach in breast cancer (Abstract 293P).These kinds of innovations can be utilized to optimize early MRD detection. 

Upfront biomarker testing, as well as accurate biomarker assessment, is critical for selecting eligible patients for appropriate treatments. More optimization and education in the field is needed to achieve seamless testing across different indications.

A tumor-agnostic approach is likely to accelerate the generation of clinical data and expand the existing pool of patients eligible for treatments based on biomarker selection. It is important to incorporate this approach into a new clinical trial framework where applicable.

Growing data are demonstrating the importance of liquid biopsy and ctDNA monitoring in the early onset of cancer, in order to detect the disease when patients have more chances of getting cured, and to prevent overtreating patients with unnecessary toxic treatments. Technological improvements of sensitivity and subsequent clinical validation are critical to ensure patients get properly tested.

AI tools are being increasingly utilized in medical care, from digital pathology to various steps of clinical trials. It is necessary to improve the quality of data and clinical validation protocols as well as to adjust regulatory frameworks to enable further development in the field.


 to talk to our team about our unique range of solutions to support end-to-end commercialization.

The 2024 European Society for Medical Oncology (ESMO) congress, a global oncology platform for clinicians, researchers, patient advocates, and the healthcare industry, once again brought representatives from all over the world together to discuss a range of medical advances in precision oncology. Our team had a great few days connecting with other industry professionals, and engaging in discussions about the critical role of ground breaking research and innovative treatments, including biomarker testing and precision oncology.

The IVD market has seen exponential growth over recent years, especially as diagnostic testing becomes ever more central to personalized medicine. The IVDR, introduced to replace the outdated In Vitro Diagnostic Directive (IVDD), has placed significant new regulatory demands on both companies and laboratories. The need for Notified Bodies that can provide certification for these diagnostics has never been more urgent. However, the process of certifying Notified Bodies has been slow to date.

The ISS designation is not only significant because it is Italy's first entry into the IVDR arena but also because the organization is no stranger to the medtech world. Already listed under the Medical Devices Regulation (MDR), ISS brings years of regulatory experience and technical expertise, particularly in areas crucial for modern diagnostics such as cancer markers, genetic testing, and companion diagnostics. This broader technical competence will be vital in assessing the next generation of tests and devices that are designed for everything from infection markers to self-testing applications.


Addressing the urgent need for Notified Bodies

With the inclusion of ISS, there are now 13 Notified Bodies designated under the IVDR, spread across Germany (4), Finland (2), the Netherlands (2), and one each in Italy, Ireland, France, Slovakia, and Austria. Despite this, the number of Notified Bodies remains insufficient to meet the growing demand for regulatory approvals, particularly given the increasing complexity of diagnostics and the rise in tests requiring formal certification. As we noted in previous discussions on the IVDR, this bottleneck in certification has become a significant challenge for the diagnostics sector, with many companies scrambling to meet the more stringent requirements on time.

The critical need for more Notified Bodies has been a recurring theme in the industry. In our previous analyses, we discussed how the IVDR has set the bar higher for clinical evidence and risk management, increasing the burden on manufacturers and the Notified Bodies themselves. The ISS designation is a step forward, but the diagnostics sector continues to face challenges in ensuring that there are enough Notified Bodies to meet market needs.


Implications for companion diagnostics and personalized medicine

For companies involved in the development of companion diagnostics, this announcement is particularly promising. As highlighted in one of our earlier posts on the growing role of companion diagnostics under IVDR, these tests are now essential for matching patients with the right therapies in personalized medicine. The ISS’s expertise in genetic testing and cancer markers aligns perfectly, enabling more rapid and efficient approval of these critical tests.

Additionally, the ISS’s broad scope of designation, covering everything from infection markers to near-patient testing, will support innovation across a wide range of diagnostic applications. This is good news for companies working on novel diagnostics aimed at improving patient outcomes in real-time clinical settings.


Looking ahead: A growing network of regulatory support

As we look to the future of the IVD industry, the addition of more notified bodies like ISS is essential. However, while the pace has been slow, the growing network of Notified Bodies suggests that the EU is making progress in addressing the multiple challenges posed by IVDR. Companies should continue to stay informed and engage with these regulatory changes to ensure that they are ready to meet the requirements of this new era in diagnostics.

The ISS’s designation is another reminder of how critical robust regulatory frameworks are for fostering innovation in diagnostics. While other challenges such the implementation of EUDAMED remain, the hope is that, as more Notified Bodies are designated across Europe, the approval processes will become more streamlined, reducing the bottlenecks that have slowed market access for much-needed diagnostics.

For more insights on the implications of IVDR and the evolving regulatory landscape, you can explore our previous articles on the subject linked below, where we delve deeper into the impact on diagnostics development, certification challenges, and the crucial role of companion

The recent announcement that Italy’s Istituto Superiore di Sanità (ISS) has been designated as the country’s first Notified Body under the EU’s In Vitro Diagnostic Regulation (IVDR) marks an important milestone for both Italy and the broader European diagnostics sector. After a year-long hiatus, the designation of ISS as the 13th organization in the EU to assess products under IVDR is a much-needed boost for an industry under increasing regulatory pressure.

Before you start the selection process, it’s essential to clearly understand your project's specific needs and long-term goals. Think about the therapeutic area, the biomarkers involved, regulatory requirements across different regions, and the timelines for drug and diagnostic development.

A partner that closely aligns with your objectives and has a proven track record in similar projects will be invaluable.

Evaluate technical expertise and capacity of your CDx partner

When evaluating potential CDx partners, their expertise and experience in the field should be your top priority. The right CDx partner should have the technical expertise to develop and validate the diagnostic, as well as the capacity to manage the scale of your project. This includes having the right technological platforms in all relevant markets, quality systems, and manufacturing capabilities. Experience in navigating the regulatory landscape for CDx approvals is equally important, as this can significantly impact your drug’s time to market.

Consider the regulatory and market access strategy

Navigating the complex landscape of regulatory approvals is a significant challenge in CDx development. Choose a partner with a solid regulatory strategy and a proven record of successful CDx submissions. If they understand the market access landscape and are able to navigate it, it can further enhance the CDx value for your therapeutic product.

Developing a CDx requires close collaboration between the pharma company and its CDx partner. A partner whose corporate culture aligns with yours and who values open, transparent communication can make this relationship much easier.

Regular updates, mutual problem-solving, and a shared commitment to the project's success are key facets of a strong partnership.

Look beyond development to commercialization

The journey of a CDx doesn’t end with its development and regulatory approval. Effective commercialization is crucial to ensure that the diagnostic reaches its target audience and is adopted by healthcare providers.

To maximize the impact of your CDx, choose a partner with a global reach, experience in market access strategies, and a strong distribution network.

Diaceutics: your partner in navigating the CDx landscape

At Diaceutics, we understand the complexities involved in bringing a targeted therapy to market. Our expertise in precision medicine, combined with our global network and data-driven approach, uniquely positions us to assist pharma in selecting the right CDx partner. Not only can we help you develop an effective CDx strategy, but we can also provide insights into market dynamics, regulatory pathways, and commercialization strategies to ensure your therapy and its companion diagnostic achieve their full potential.

Choosing the right CDx partner is essential for the success of your targeted therapy. By considering these critical points and leveraging the expertise of a seasoned partner like Diaceutics, you can navigate this journey with confidence.

In the quest to bring more personalized treatment options to patients, the right collaborations can make all the difference. Reach out to Diaceutics today, and let’s discuss how we can support your CDx strategy and help you select the ideal partner to bring your targeted therapy to those who need it most.

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Developing a companion diagnostic (CDx) is a vital step for pharma looking to launch targeted therapies. These diagnostics help not only identify patients most likely to benefit from a specific drug but also boost drug efficacy and patient safety. However, given the complexity and regulatory intricacies involved, choosing the right CDx partner can be time consuming and difficult.

At Diaceutics, we leverage our extensive experience and deep industry insights to guide pharma companies through this critical decision. Here's how to ensure you pick the right CDx partner for your drug's go-to-market journey.

Insights

Overcome the challenges of Implementing New Biomarker Tests in Labs

Early awareness campaigns obtain better results

Celebrating 30 years of ALK: From discovery to precision medicine breakthroughs

ESMO 2024 Highlights

ISS Named As Italy’s First Notified Body Under the EU's IVD Regulation: What This Means for the Diagnostics Landscape

Selecting the right CDx partner: Insights from Diaceutics