February 2018 Edition Vol.11, Issue 2

Precision Oncology: What Recent Advancements Mean for the Industry

By Maria Whitman, Jon Roffman & Sharon Karlsberg, ZS Associates

Across healthcare, the promise of precision medicine has been a looming target for more than two decades. Oncology has been the area of acute focus as cure remains elusive due to the intelligence and ever-evolving permutations of this disease. That said, we have seen major leaps in precision oncology since the late 1990s:

• The advent of targeted therapies—Herceptin in HER2+ breast cancer and Gleevec in chronic myeloid leukemia (CML), two treatments that radically changed the prognosis of those diseases
• The appearance of gene panel tests—Predicts patient responsiveness to therapy and enable physicians to pair patients with the drugs that are most likely to be effective for them
• The rise of companion diagnostics to sub-segment populations for individual therapies—In lung cancer alone, researchers have identified four “actionable mutations” and biomarkers that align to 10-plus commercially available therapeutics

Scientific setbacks have also demonstrated limits to what may be possible. Nearly two decades ago, early interventions in the gene therapy space were halted due to safety concerns. Striking the right balance of efficacy and safety with precision medicine, especially given the toxicity of some combination targeted regimens, continues to be a sensitive topic for oncologists worldwide.

 

2017: The Future Is Now

Although we’ve seen major leaps in precision oncology, significant debate on whether its promise can be achieved remains, as well as the overarching impact it may have on cancer as a disease. Still, we celebrate 2017, which definitively helped in the advancement of understanding the science and delivery of precision oncology.

Here’s how:

• Approved genetic classification with a balance of scale and precision: Prior to 2017, fragmentation abounded in the usage of next-generation diagnostic technologies, including next-generation sequencing (NGS) and “hotspot” gene panels that yield insight into the breadth and depth of mutations affecting cancer. Without an FDA approval, providers and patients struggled to obtain reimbursement for these costly tests. In November 2017, the FDA approved FoundationOne CDx, a commercially available test that can detect mutations in 324 genes in any tumor type. CMS’s simultaneous announcement of national coverage for the test dramatically shifted the impact of NGS. The combined FDA and CMS actions will both expand the number of patients treated in a more precision-guided way and accelerate data collected from cancer patients for better precision-guided therapies in the future.
• The advancement of precision medicine with gene therapy approvals in CAR-Ts: After several years of scientific promise, stunning clinical highs and a few disheartening, late-phase trial lows, the industry celebrated the FDA approval of two new cancer therapies in 2017 based on chimeric antigen receptor T-cell (CAR-T) technology: Novartis’ Kymriah for pediatric acute lymphoblastic leukemia (ALL) and Kite’s Yescarta for relapsed diffuse large B-cell lymphoma (DLBCL). Despite Juno’s CAR-T setbacks, Novartis and Kite successfully leveraged gene therapy science to make personalized treatments available for patients with two debilitating forms of hematologic malignancies. Whether CAR-T cell therapy will work in solid tumors remains one of the unanswered questions.
• FDA evolution on key areas of trial design: Clinical trial design has likewise kept pace with rapid changes in drug and diagnostic development. Clearly acknowledging that oncologists often characterize cancer based on genes rather than on the tissue of origin alone, 2017 saw the FDA’s first approval of a drug tested via “basket trial” design. In May, the FDA approved Keytruda for patients with a common biomarker, microsatellite instability-high (MSI-high) tumor, after the pivotal trial showed efficacy across a variety of solid tumors (colorectal, gastric, breast, prostate, bladder and more). The availability of both basket and umbrella trials (such as I-SPY2 in early stage breast cancer) in the clinical development library ensures that more cancer patients can receive the benefits of personalized medicine, regardless of the tumor type or mutational driver.
• Real-world-evidence-centered approval: Although the approval of Roche’s Actemra/RoActemra (tocilizumab) for the treatment of CAR T-cell-induced cytokine release syndrome itself is not a personalized medicine advancement, it’s an approval based on retrospective analysis of pooled outcomes data from CAR-T clinical trials. This approval came in concert with Kymriah’s approval and signals the considerable opportunities for leveraging analytics and data moving forward.

 

What Does It All Mean?

With progress comes change. These advancements bring us closer to precision oncology and supporting patients in need. They also bring challenge and change for many stakeholders. Unquestionably, however, companies that integrate companion diagnostics into their clinical trial and drug development processes are more likely to succeed in the fight against cancer. How prepared is your organization for this shift to precision medicine on a broad scale?

 

Here are four key implications of precision oncology advancements on treatment and commercialization:

1. Patient identification on steroids: The ability to further stratify and classify patients does not yet translate to the obvious decision of what to do with that patient in a truly personalized fashion. The data need to be more reliable and deterministic. The PD-L1 biomarker has received mixed reviews from oncologists, balancing enthusiasm for the benefits to high expressers with dismay by the lack of consistency across PD-L1 diagnostic antibodies. Successful commercialization increasingly will require cutting through the clutter and making it easy for cancer physicians to understand which test most accurately predicts which drug is right for the patient in front of them.
2. Rising stakeholders in care coordination: Precision oncology advancements mean changes to influencers and participants in the traditional care team. Pathologists will be more critical stakeholders moving forward, influencing when, what, and where companion diagnostic testing is done. Manufacturers will need to engage pathologists as partners to ensure that the eligible patient population is reached. Moreover, CAR-Ts have already shown that precision oncology requires intense coordination across not only the clinical care team and payers, but also manufacturers in an unprecedented way. In a system accustomed to separation, centers of excellence and manufacturers need to come together and find meaningful ways to connect data systems, and logistical and safety protocols, etc. to enable the scale required as more personalized therapies are approved for higher volumes of patients.
3. Facing the cost reality: Just as cost and therapeutic value accompany presentations at ASCO and ASH, we can’t discuss advances in precision oncology without considering implications for the healthcare system and individual patient costs. Each of these innovations in precision oncology adds a layer to an already high-cost disease, from genetic testing and counseling to 3-D radiographic screening, NGS testing, multidrug combo treatment and supportive care regimens, liquid biopsy monitoring for recurrence, and more. At the same time, these diagnostic interventions promise to reduce spending on therapies that will not benefit a specific patient. Cost is embedded across the system, and we need to start looking more closely at episodes of care. On the manufacturer side, Novartis opened a door with its CMS outcomes-based agreement for Kymriah in pediatric ALL. Beginning in 2018, we anticipate that more payers will ask drug developers to engage in outcomes-based contracts moving forward to help mitigate the cost burden of novel therapeutics.
4. An R&D revolution: These examples from 2017, along with the continued high percentage of approvals that are accelerated through one of the FDA mechanisms, shows a willingness to continue to evolve the trial design and approval processes. Manufacturers need to step back and consider the evolution on their end as well, adjusting often cumbersome legacy processes to enable the agility and coordination of these newer approaches. They will need to be more forward-looking in diagnostic protocols, endpoints considered, and even supplemental evidence planning to ensure relevance and competitive differentiation at the time of launch moving forward.

 

Seeing Around the Corner

Manufacturers are already looking around the corner and jockeying for position in a crowded, precision-guided marketplace. In mid-January, Pfizer announced a broad partnership with Foundation Medicine, which will develop companion diagnostics for Pfizer’s full oncology portfolio. This is not a harbinger of things to come. This deal cements the fact that pharma’s biggest players recognize the importance of precision medicine in oncology.

Advancements on the horizon will continue to evolve the trend from MRD testing and high mutational burden to next-generation gene-editing technologies. There are also clear markers for an increasingly complex and competitive therapeutic landscape. Today, 87% of oncology therapies in development are targeted, and a disproportionate amount of investment continues to be in overlap areas across manufacturers.

As oncologists are armed with increasingly precision-guided diagnostic and treatment options, we can envision a shift in the structure of oncology treatment. Imagine biomarker-specific KOLs or centers of excellence in much the same way that we see tumor-site-specific (such as lung or breast) KOLs today. How will patients flow through such a system, and how will manufacturers identify and intervene to deliver the right therapies to those patients?

Additionally, with increasingly reliable test results and a multitude of therapeutic options, treatment decisions are likely to be influenced increasingly (perhaps predominantly?) by algorithms and artificial intelligence. How will manufacturers ensure that their therapies are optimally positioned to maximize utilization in the patients who will benefit the most?

As the Pfizer/Foundation Medicine deal illustrates, manufacturers need to start to prepare now for their customers’ evolution. There are still many uncertainties, so agility will be critical. However, it’s clear that the future will bring more precision to oncology treatment patients, and this will require manufacturers to be more precise in how they engage customers—bringing the right information (more specific and deterministic) to the right stakeholders (not just oncologists but pathologists, algorithm influencers, computer programmers and more) at the right time (each point in the patient journey through an increasingly dynamic healthcare system). Are you ready for the future?

About the Contributors

Maria Whitman is a managing principal of ZS’ specialty therapeutics work providing leadership in the oncology, orphan / rare, biosimilars, cell & gene, CDx/MDx and other critical spaces in this dynamic and intensifying area. Based in Philadelphia, Maria brings nearly 20 years of experience in the healthcare industry. She works with established and emerging companies on a range of strategy, marketing & sales, organizational capability building and excellence, value & access, launch excellence, customer insight and experience and early development / med-affairs / R&D issue areas. Prior to ZS, Maria worked in direct response and relationship marketing in and outside the healthcare space, including focus on customer behavior and patient programming. Maria earned her MBA with honors in marketing and healthcare systems from The Wharton School at the University of Pennsylvania and a B.S. in marketing (maxima cum laude) from La Salle University. In 2015, Maria was named one of Consulting Magazine’s Top Women in Consulting.

 

Jon Roffman is the managing principal at ZS’s Boston office and is the global lead for ZS’s oncology practice. He partners with clients to address sales and marketing issues in the oncology marketplace, with an emphasis on customer engagement and customer experience strategy, planning and execution. Jon has led many initiatives to design innovative customer engagement and deployment models in oncology. Jon also has advised more than 20 oncology companies on sales and marketing strategy issues, ranging from small biotechnology companies launching their first products to large pharmaceutical companies building out their portfolio. Prior to joining ZS in 2005, Jon earned his MBA from NYU’s Stern School of Business and his B.S. in electrical engineering from Cornell University.

 

 

Sharon Karlsberg is a principal in ZS’s San Francisco office. She has more than 20 years of experience in the healthcare industry, and she’s a founding member of the ZS oncology team. Sharon works on a variety of marketing and commercial strategy issues with leading biopharmaceutical manufacturers. Her experience includes market research, brand strategy, competitive readiness and scenario planning, biosimilars and new product launch. Sharon’s therapeutic area of expertise spans many specialty markets, with significant depth in oncology, both solid tumors and hematological malignancies. Sharon joined ZS in 2004. Previously, she worked in market research for the medical diagnostics industry, public and investor relations for the biotechnology sector, and product marketing at Boston Scientific, Neurovascular. Sharon holds an MBA and certificate in health management from the University of California Berkeley’s Haas School of Business, and a bachelor’s in genetics and cell biology from Dartmouth College.

 

ZS is the world’s largest firm focused exclusively on helping companies improve overall performance and grow revenue and market share through end-to-end sales and marketing solutions—from customer insights and strategy, to analytics, operations and technology. More than 5,000 ZS professionals in 22 offices worldwide draw on deep industry and domain expertise to deliver impact for clients across multiple industries. To learn more, visit www.zs.com or follow us on Twitter and LinkedIn.