Getting Personal with Precision Medicine – PharmaVOICE

NeuroPointDX was mentioned, and our CEO Elizabeth Donley was quoted, in this article about precision medicine.

Research on biologics, the study of the human genome, and the development of precision diagnostic tools and software have led to new hopes for the development of promising precision medicine. At the same time, the life-sciences commercial sector is still struggling with the challenges of payment structures and value assessment frameworks.

As originally conceived, personalized medicine referred to the tailoring of medical treatment to the individual characteristics of each patient (as defined by President Obama’s Council of Advisors on Science and Technology). This ultimately led to a shift in the clinical treatment paradigm from a trial-and-error approach to “the right drug, for the right patient, at the right time.”

According to a McKinsey report, a combination of public investment, biotechnology development, and digitization of health profiles has evolved personalization beyond therapy selection and into the realm of drug discovery, how care is planned for and delivered, and increasingly, to how consumers engage with companies seeking to improve health.

The right drug for the right patient has since evolved to an approach that takes into account individual differences in people’s genes, environments, and lifestyles. This approach received a boost from President Obama’s Precision Medicine Initiative. The Initiative launched in 2015 with $215 million investment to pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.

According to the Precision Medicine Initiative, precision medicine is “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.” This effort leads to better selection of disease targets and identification of patient populations that demonstrate improved clinical outcomes.

According to the National Research Council, precision medicine refers to the tailoring of medical treatment to the individual characteristics of each patient. It does not literally mean the creation of drugs or medical devices that are unique to a patient, but rather the ability to classify individuals into subpopulations that differ in their susceptability to a particular disease or in their response to a specific treatment.

Personalized medicine, on the other hand, is a multi-faceted approach to patient care that not only improves the ability to diagnose and treat disease, but offers the potential to detect disease at an earlier stage, when it is easier to treat effectively, according to the Personalized Medicine Coalition.

The Precision Medicine Era

Precision medicine holds great promise for improving patient health outcomes. Experts say we are just at the beginning of the precision medicine era. Further, precision medicine will have a major impact on how doctors and patients think about disease and how patients are treated.

Over the past five years, healthcare’s collective understanding of what constitutes precision medicine has evolved from the simple mandate of “one patient, one drug” to a more complex data, analytics, and business model ecosystem.

Precision medicine research is being driven by a number of factors, including accelerated scientific discovery in genomics and immunology, increased availability of patient data, and advancements in informatics and artificial intelligence.

About 7% to 10% of patients today are able to benefit from an approved precision medicine, says Dan Rhodes, Ph.D., CEO and co-founder, Strata Oncology, which has developed a next-generation sequencing based screening test.

“The hope is that these new precision medicines will benefit all cancer patients,” he says. “Even with emerging precision medicines in clinical trials representing another 20% or 30% of patients, there are still many patients not benefiting from precision medicine.”

Dr. Rhodes predicts that in the next couple of years there will be more single agent and combined immunotherapy studies leveraging biomarkers to hone in on responsive patient populations.

“Over the next five years we’ll see precision medicine approvals go beyond the targeted therapy space of oncogenic drivers of cancer and transition to the immunotherapy space,” he says.

The opportunities for precision medicine are endless, says Alif Saleh, CEO of Scipher Medicine, which is developing a diagnostic platform that analyzes RNA data from blood samples.

“About 90% of patients who are prescribed the top top 10 selling drugs in the world don’t actually respond to therapy,” he says. “This tells you the size of the problem. We are in the beginning of an era where more and more precision medicine technologies will come into the market to solve these problems.”

While many novel approaches are still in early stages, it’s important to keep in mind that the first immune checkpoint inhibitor was approved only eight years ago, and only two years ago did we see the first-ever therapy approved based on genetics rather than tumor type, says Chad Clark, president of Precision for Medicine.

“These advancements extend beyond oncology, with the first gene therapy approval just 15 months ago,” he says. “There are now trials under way with cancer vaccines, cell and gene therapies, gene editing, and many other novel approaches. While it remains to be seen which of these strategies will have the greatest impact, there are significant indicators that many of them will lead to approvals with lifesaving or life-altering results.”

Eventually there won’t be a distinction between precision medicine and medicine, says Matthew De Silva, founder and CEO, Notable Labs. “Identifying and delivering the best possible treatment for an individual patient is a paradigm that makes sense regardless of the disease category,” he adds.

Precision Medicine Research Trends

Recent regulatory nods—including Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo, approved in 2017—mark important milestones for cancer treatments approved based on a common biomarker rather than the location in the body where the tumor originated.

A PwC survey of global leaders in the pharmaceuticals industry shows that companies are aware of the promise: 92% identified precision medicine as an opportunity, and 84% have it on their corporate agenda. Most point to clear advantages in drug development, such as reducing time-to-market and making R&D processes more efficient. Even a conservative estimate puts the cost-savings in drug development at 17%, leading to a potential annual savings of $26 billion worldwide.

Samit Hirawat, M.D., executive VP, head of oncology global development at Novartis, says very few of the molecules in the company’s pipeline don’t have a precision medicine component.

“Our focus is to identify patients who are going to have outcome improvements if we are able to identify molecules that are specific to genetic markers,” he says. “In breast cancer, for example, ur efforts in precision medicine have been ongoing for some time. Novartis was the first company to present positive data for progression-free survival, the primary endpoint of the study for patients with hormone receptor-positive HER2-negative advanced breast cancer whose tumors have harbored a PI3-kinase mutation.”

Dr. Hirawat says Novartis has an in-house team in Oncology Precision Medicine that works with the diagnostic division called Navigate. These teams work on assay development to support clinical trials and work with partners for companion diagnostics.

“Our vision always has been to have a more holistic approach to looking at a tumor rather than the specificity and identification of the mutations,” he says. “We want to understand the factors that can drive resistance or response of the therapy to the tumor.

“These are not only critical to today’s drug development, but allow us to identify mechanisms that we need to target for tomorrow’s drug development.”

Researchers from Grand View Research say trends such as cost-effective genomic and molecular biology testing methods, increasing prevalence of cancer and rare diseases, and rising use of big data in precision medicine—diagnostics/therapeutics—market size is expected to reach $85.5 billion by 2025 at a 9.9% CAGR.

Industry experts say oncology has been an important beachhead for precision medicine due to efforts to understand how unique each patient is and how much the same disease can vary from patient to patient or over time within the same patient.

“In oncology we have shown a whole host of specific biomarkers and specific mechanisms of actions for drug-able targets,” says Jordan Clark, chief technical officer, Diaceutics, a data analytics and implementation services company. Specifically, the company focuses on the diagnostic testing required to guide selection of such medicines.

“Looking at clinicaltrials.gov, about 73% of clinical trials in oncology are biomarker-enabled,” he says. “This shows the business model in oncology has changed to one where precision medicine is now the predominant way of investigating new assets and drugs.”

But he says precision medicine is lagging behind in other therapeutic areas, such as cardiology, autoimmune, and CNS disease. “For example, with Alzheimer’s disease, there has been a couple of high-profile clinical trial failures over the last year with an unknown convincing biomarker strategy. There is still a great need to understand the root causes of Alzheimer’s disease and the genetic and increasingly important multi-omics that are contributing to Alzheimer’s disease.”

Jeffrey Hodge, VP of development solutions, oncology center of excellence, IQVIA, says precision medicine will continue to grow in importance in oncology because of wider patient profiling and greater pressure to match patients to drugs.

“I anticipate this trend to continue as more investment—pharmaceutical and venture capital—is made in oncology than other therapeutic areas combined,” he says. “Efforts in immune and inflammatory disease linking precision medicine have been ongoing for some time without great success. Rare disease is certainly a major growth area now, but targeting genetic diseases requires a genetic diagnosis by definition in most cases.

“Neurodegenerative diseases are also an important focus for precision medicine with new treatments needed.”

Precision Medicine Beyond Oncology

Industry experts say researchers are beginning to consider precision medicines for non-oncologic diseases. This has resulted in greater focus on immunological, genetic, and rare diseases.

The combination of classical biology methods brought together with machine-learning methodologies are going to push precision medicine even further by better characterizing disease, says Jon Armstrong, chief scientific offers of Cofactor Genomics, a predictive immune modeling company.

A company developing diagnostics for conditions beyond oncology is NeuroPointDX. The company, a business unit of Stemina Biomarker Discovery, is bringing a precision medicine approach to the diagnosis and treatment of neurological disorders through the application of world-class metabolomics.

The company’s current focus is autism spectrum disorder (ASD). NeuroPointDX has developed and is commercializing testing panels to aid in the early diagnosis of ASD through its CLIA-certified laboratory.

NeuroPointDX’s CEO and co-founder Elizabeth Donley, who has a 22-year-old son with autism, says: “I know the struggle families face in getting a diagnosis and understanding the treatments to try. There’s still a lot of confusion and lack of precision around how families and physicians address autism. Families read on the Internet about potential treatments others are trying, including modified diets, dietary supplements, attention deficit medicines, hyperbaric chamber treatments, and psychotropic drugs. We believed that there was an opportunity to better understand the underlying biology of this disorder and then to pair that with therapies.”

The NPDX ASD test identifies children with specific metabolic subtypes associated with ASD. The test may be used to screen children as young as 18 months. The test also provides metabolic information that may be used to inform a more precise treatment strategy for a child with ASD. The metabolic subtypes were identified and validated in children 18 to 48 months old in the Children’s Autism Metabolome Project (CAMP), the largest clinical study of metabolism of children with ASD conducted to date.

“CAMP has further advanced the hypothesis that children with autism have a different profile from a metabolism perspective,” Ms. Donley explains. “We don’t know why there is a difference in metabolism, but understanding that there is a difference and what that difference is offers us an opportunity for the first time to pair treatment based on metabolism.”

AstraZeneca’s spin-out Entasis Therapeutics is applying precision medicine to antibiotic resistance. The biotech company aims to restore health to people affected by serious pathogens.

“Traditionally, we treat patients according to the body site where the infection occurs, such as pneumonia or urinary tract infections, and often without knowing what pathogen is causing the infection,” says Manos Perros, Ph.D., president and CEO, Entasis Therapeutics. “We have been locked in the model of using broad-spectrum antibiotics to cure large numbers of patients without havin to understand what infection it is.”

Entasis is approaching the research of anti-infectives differently. “Our products are targeting a specific pathogen or group of pathogens,” he explains. “For instance, our lead program is targeting a bacterium called Acinetobacter, which can be found in pneumonia but also in the blood, in the urinary tract, as well as in the skin.”

With a pathogen-targeted approach for serious, drug-resistant infections, Entasis is tackling some of the most serious infections caused by Gram-negative bacteria. The company’s lead product candidate is ETX2514SUL targeting Acinetobacter baumannii infections associated with high mortality, rapidly increasing rates of antibiotic resistance, growing significance as a hospital-acquired infection, and limited treatment options. Entasis is partnering with Zai Lab in China for this research.

In early April, Entasis initiated its global pivotal Phase III ATTACK trial for the treatment of patients with pneumonia and bloodstream infections cause by carbapenem-resistant A. baumannii. The trial plans to enroll 300 patients worldwide, with top-line data readout expected in the second half of 2020. The company believes this single Phase III trial could be sufficient to support the filling of a new drug application with regulatory authorities in both the U.S. and Europe.

A second product candidate is zoliflodacin, which is targeting Neisseria gonorrhoeae (which causes uncomplicated gonorrhea), and Phase III trials are expected to begin this year in partnership with GARDP. A third product is an oral agent, ETX0282CPDP, targeting multi-drug resistant Enterobacteriaceae infections in partnership with CARB-X. Results from Phase I are expected in the first half of 2019.

“From what we have seen so far, we expect our drug candidates to be not only potent but also more selective and, therefore, better-tolerated,” Dr. Perros says. “Broad-spectrum, largely generic antibiotics will still work for a majority of patients, but for those patients for whom those drugs no longer work, we will have much more targeted, tailored, and specific treatments that may save their lives.”

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