June Spotlight

Holding True to the Price-Cap Pledge

As in previous years, 2018 started with more than 30 drugs increasing in price on the US market. However, data and analysis firm GlobalData observes that criticism from politicians and the public seems to be keeping the industry to a 10% self-imposed price-hike limit. It began with Allergan CEO Brent Saunders pledging to police pricing in 2016, when he stated that his company would limit itself to one price increase per year and only by single-digit percentages. And none of the price hikes seen so far this year have exceeded 9.9%. Companies such as Teva, Cellectis, Insys, Synergy, and Supernus all have raised prices while staying within the 10% limit. Allergan meanwhile has raised the price of 18 medications by 9.5%.

GlobalData healthcare analyst Alice Stevens says, “As rising drug prices continue to be a major cause for discord in the United States, self-regulation of price hikes could help the industry prevent regulatory reform.”

This conservative approach to price increases is merely a spoken agreement among drug makers. Not every company will consider it to be an obligation. In 2017 for example, Pfizer and Celgene raised some of their prices by 19.8% and 27.5%, respectively. “It remains unclear how long this social contract will last,” Stevens cautions. “Although many companies seem to be willing to adhere to Allergan’s pledge at present, the need for higher revenues may see another rise in drug prices before the year is out.”

Cell and Gene Therapies Developments in the United Kingdom and Japan

The Cell and Gene Therapy Catapult (CGTC) will support three UK sites that have been awarded funding to form a network of advanced therapies treatment centers after an Innovate UK competition. These joint ventures include industry, academic, and National Health Service (NHS) partners: Innovate Manchester Advanced Therapy Centre Hub (iMATCH), the Midlands-Wales Advanced Therapy Treatment Centre (MW-ATTC, covering Birmingham, Wales, and Nottingham), and the Northern Alliance Advanced Therapies Treatment Centre (NAATTC, covering Scotland, Newcastle, and Leeds).

“This network represents continued progress of advanced therapies from lab to patient,” said Keith Thompson, CGTC’s chief executive. “We will help to join up manufacturing centers to these new treatment centers and establish new vein-to-vein clinical pathways. Our manufacturing center (which will open fully in 2018) is expected to help pave the way at scale for industrialization and commercialization of cell and gene medicines.”

The centers have been awarded £21 million from the UK Industrial Strategy Challenge Fund, with further funding available to support individual projects. That money comes from a £146 million allocation set aside under the Medicines Manufacturing Challenge to develop technologies for manufacturing innovative medicines for arthritis, blindness, cancer, heart failure, liver disease, neurological conditions, peripheral vascular disease, and rare pediatric diseases.

Innovate UK’s chief executive Ruth McKernan said her group’s investment “is a crucial component of the government’s modern industrial strategy.” It will “support cutting-edge cell and gene science to tackle some of the most debilitating conditions that patients face today.”

Leveraging the unique skills of the industrial partners, the centers will work together to increase patient access to advanced therapies on a national scale while establishing best practices for near-patient manufacturing and for safe, effective delivery of those therapies. The centers intend to create robust, integrated supply chains with systems for traceability and tracking of both products and patients. That should ensure best practices for patient follow-up and data capture. This will be the first such integrated system in the country and will position it as a leader in clinical trials and routine delivery of cell and gene therapies. Resulting data could support reimbursement and payment systems, the next significant barrier for these sometimes curative therapies.

Complex advanced therapies present a business challenge to traditional healthcare models. Expanding small-scale clinical trials for such therapies is a complicated task for individual organizations. As a goal of this three-year project, industry partners will work together with the public sector and CGTC to develop necessary processes, skilled staff, and infrastructure for making these products at scale as more of them move from clinical trials to market.

CGTC Partnership with the Japanese Society for Regenerative Medicine: In February, CGTC also signed a memorandum of understanding with the Japanese Society for Regenerative Medicine (JSRM) to advance regenerative medicine in both the United Kingdom and Japan through collaboration. The organizations will share information on technologies, policies, and legal issues while assisting one another in sponsoring and hosting meetings.

The CGTC works with partners in academia and industry to ensure that life-changing therapies can be developed for use in health services around the world. JSRM is the largest society for regenerative medicine in the world, with about 6,000 members involved in basic and clinical medicine, tissue engineering and cell biology, and fields in the humanities and sociology. Participating members hail from academia, industry, and government. JSRM activities go beyond publishing academic journals to making policy proposals as a community, engaging in voluntary research and development, promoting research, and exploring new avenues of collaboration with patients and citizens.

“JSRM is delivering many projects to commercialize regenerative medicine, and I am sure that it has much to learn from activities of CGT Catapult,” said Yoshiki Sawa, JSRM president.

ASTM: Closer Partnership Needed for Standards and Innovation Communities

In March, ASTM International released a white paper titled, Standards Development: Enabling Manufacturing Innovation and Accelerating Commercialization. The free paper (available at www.astm.org/ABOUT/white_papers) provides a vision for optimal partnership and interaction among the global standardization and innovation communities. In particular, it emphasizes how they must be more proactive to keep pace with marketplace innovation.

“More than ever before, businesses throughout the world need high-quality standards that evolve in tandem with rapid advances in cutting-edge fields,” said ASTM president Katharine Morgan. “Together, we can meet that challenge by creating aligned road maps, by maximizing participation in standards development, and more.”

The white paper explains the value that a collaborative and integrated approach to voluntary standards development can bring to innovation initiatives. Specifically, it emphasizes

The paper also provides examples of how its approach could benefit global leaders involved in standardization and related R&D. These highlight how collaborative approaches already are succeeding in the field of additive manufacturing (3D printing).

“High-quality technical standards are the foundation for long-term commercial success and key to accelerating deployment of advanced manufacturing technologies,” says John Vickers, principal technologist for advanced manufacturing at NASA. “If we strengthen the relationship between R&D and standardization activities, we will dramatically improve the competitiveness of US advanced manufacturing industries.”

Influenza Vaccine Research Funding Needed

The latest flu season was an especially deadly one. Widespread across 48 states, the current strain has killed 97 children so far. Meanwhile, the 2017–2018 vaccine has been only 36% effective, according to a study by the US Centers for Disease Control. By comparison, the 2016–2017 vaccine was 40% effective, and the 2015–2016 vaccine was 48% effective.

A large number of physicians, scientists, and researchers are looking for solutions. Although the current administration has been silent on the issue, eight senators have introduced the Flu Vaccine Act, calling for US$1 billion in research toward creation of a universal flu vaccine.

The Science Coalition, a member organization of over 50 universities, advocates for robust federal funding for basic science such as that required to fight influenza. Many member universities are working on developing a universal flu vaccine: University of Nebraska, University of California in Los Angeles, University of Washington, University of Rochester, and Rockefeller University.

Given the severity and persistence of the flu year in and year out, creation of a universal vaccine is a National Institutes of Health (NIH) priority. However, in 2018 the NIH has only $32 million for such research. Consider that $1 billion was spent to develop an HIV vaccine, and multiple billions were spent on Ebola and Zika vaccines. These groups insist that the federal government must make funding scientific research on influenza a priority.

Digital Trials, Partnerships, and Combination Therapies for Cancer Immunotherapy

Collaborations among traditional drug developers, cancer-treatment professionals, and other disciplines have gained momentum. Examples include the IBM Watson supercomputer helping physicians make treatment decisions and databases such as ASCO’s CancerLinQ assisting oncologists in monitoring and analyzing patient data.

GlobalData predicts more of the same in 2018. Oncology and hematology director Fern Barkalow says, ‘‘These approaches could not come at a better time, as the global incidence of many cancers is still quite high. Additionally, many cancer types continue to have areas of high unmet need despite the launch of more effective and safer drug therapies for various diseases.‘’

In just the first month of 2018, a search of GlobalData’s Healthcare Intelligence Center counted more than 800 clinical trials running in the top 10 locations worldwide, half of those in the United States. Top indications involved represent a mixture of more prevalent cancers — e.g., breast cancer (22%) and non–small-cell lung cancer (NSCLC, 18%) — and rarer forms with greater levels of unmet needs, such as gastric cancer (10%), acute myelocytic leukemia (8%), and ovarian cancer (6%).

Clinical trials remain the mainstay of drug testing; however, they are a major source of drug development costs. In a landmark digital medicine trial in 2017, patients with solid tumors enrolled in a large, randomized study conducted at Memorial Sloan Kettering Cancer Center. Those who used a web-based tool to report events in real time showed a higher overall survival than those treated with the same drug who did not use it. GlobalData forecasts that digital advances will facilitate changes in clinical trial design and outcomes, streamlining development and reducing costs.

Barkalow concludes, ‘’The stage is set in 2018 for digital-medicine technology to have a significant impact on the cancer landscape by transforming the way cancer drugs are developed and tested for approval, as well as the ways in which cancer patients are treated during routine practice.’’

Immunotherapy Could Be the Key to Treating Aggressive Brain Tumors: A research group at the UK University of Leeds have treated aggressive brain tumors with viruses. GlobalData claims that such an immunotherapy treatment approach could be the way forward for brain cancer.

Senior oncology analyst Maxime Bourgognon says, “This approach works by stimulating the body’s immune system to fight the tumors. In a proof-of-principle study, a UK-based research group has shown the potential of injecting intravenously an oncolytic virus in patients with brain tumors to enhance the potency of immunotherapy. There is a strong rationale for priming the immune response by releasing a large amount of antigens, using oncolytic viruses, and unlocking the T-cell immune response, based on immune checkpoint inhibitors. I anticipate opportunities remain for immunotherapies to improve the survival of patients with brain tumors.”

Combinatory approaches such as oncolytic virus and checkpoint modulators could become a critical strategy to improve the prognosis of patients with brain tumors. Bourgognon concludes that checkpoint inhibitors should benefit from such an approach.

Competition among Checkpoint-Inhibitor Developers Ahead: GlobalData expects programmed death-ligand 1 (PD-L1) inhibitors to dominate the market through the coming decade. The latest strategy in cancer immunotherapy shows promising results for solid tumors. PD-L1 inhibitors are being tested for treatment of pancreatic cancer, acute myeloid leukemia, and NSCLC in combination trials and as adjuvants for melanoma and renal cell carcinoma.

GlobalData healthcare analyst Eva Grey says that to date the number of checkpoint inhibitors in trials has grown over threefold since early 2015. With 21 targets under development as immune checkpoint modulators, most trials (>90%) are going after programmed cell-death protein 1 (PD-1), PD-L1, and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) targets. Grey continues, “Checkpoint therapies have attracted major companies with many opportunities for exponential growth in both clinical and market success.’’

Approved products include Merck’s Keytruda and the Opdivo treatment jointly developed by BristolMyers Squibb and Ono Pharmaceuticals, as well as BMS’s Yervoy antibody. The former two have led the number of approved indications for PD-L1 checkpoint inhibitors, with five and six approvals, respectively. Researchers are exploring the use of PD-L1 inhibitors with chemotherapy or as backbone therapies for immunooncology candidates.

Grey adds, ‘‘Checkpoint therapies show a range of uses in clinical research, but there is plenty of market share available to adopt these drugs. The benefits of market access for checkpoint inhibitors are plentiful; developers have the upper hand in an approach to markets and gaining first-to-market and first-in-class approvals.’’

BMS and Nektar Cancer Treatment Collaboration Lays Out New Path for Combination Therapies: Early this year, Nektar Therapeutics and BMS announced a partnership deal worth up to $3.6 billion involving Nektar’s NKTR-214, an early-stage immunooncology drug designed to stimulate expansion of T cells. Under the terms of the agreement, BMS will have an exclusive development period to investigate combination regimens of NKTR-214 and its own in-house flagship drugs Opdivo (nivolumab) and Yervoy (ipilimumab) in 20 indications. This ambitious development program will span nine tumor types, including NSCLC, melanoma, bladder cancer, and breast cancer. Most of those solid tumors represent highly competitive markets, with drugs based on multiple targets approved for the same indications.

As companies exhaust label expansion for monotherapy applications of their PD-1/PD-L1 drugs, they are looking both internally and externally for combination-regimen candidates that could boost the clinical efficacy of their drugs and gain further market approvals. With five PD-1/PD-L1 drugs already approved and more coming down the pipeline, this creates a competitive scenario in which companies with early stage drugs could partner with multiple others for the same indication. Thus far, such partnerships have been largely nonexclusive.

Incyte has partnered with both BMS and Merck for separate Opdivo and Keytruda (pembrolizumab) trials combining Incyte’s indoleamine 2,3-dioxygenase (IDO) inhibitor (epacadostat) for treatment of melanoma, NSCLC, and head-and-neck cancer. Incyte also is working with AstraZeneca and Roche for combination approaches in NSCLC. The lack of exclusivity goes both ways, with AstraZeneca and NewLink Genetics also working on an IDO inhibitor to treat pancreatic cancer. NewLink Genetics has partnered with Roche to develop next-generation IDO and tryptophan-2,3-dioxygenase (TDO) pathway inhibitors.

Incyte has ongoing and planned pivotal trials for melanoma using epacadostat–Opdivo or –Keytruda combinations. Without head-to-head trial comparisons, it will be interesting to see whether the results of those parallel combination trials will be used to evaluate the superiority of PD-1/PD-L1 drugs in a particular indication.

The high volume of partnerships established between companies with early stage immunooncology drugs and companies with established products shows the frenetic pace of deal-making in this space. By undertaking multiple partnerships, companies can hedge their bets as they wait for more clinical data to become available. However, this new exclusive partnership of BMS and Nektar could spur other major players such as Merck, Roche, and AstraZeneca to seek out their own exclusivity deals in the near future.

For more in-depth analysis, check out GlobalData online at www.globaldata.com.