Blog Archives

By Mark J. Alles, Celgene Chairman and Chief Executive Officer

A few decades ago, drug discovery was, for the most part, a matter of trial and error. The world’s most successful pharmaceutical companies would often collect dirt from far-flung locales and screen that soil or sand for medically active components. Biology was often a secondary concern. It was the speed of trial and error that was important.

Today, drug discovery is more targeted and intentional, building on a wealth of data that has grown exponentially since the early days of trial and error. Our knowledge of cell biology and genomics is now sufficiently advanced that it is possible to create medicines based on our individual immune cells or genetic profile. These advances promise patient-tailored medicines, such as the new CAR T therapies that “train” the patient’s own immune system to fight cancer, that have the potential to transform how cancer is treated.

This kind of innovation, however, requires investment to be sustained. Both the basic science and the delivery of treatments require investment to foster the next generation of therapies. The challenge is ensuring access to and reimbursement for those new medicines, thereby enabling innovators to reinvest in research and development. This is the virtuous cycle of innovation.

Mark Alles

Mark J. ALLES, CELGENE CHAIRMAN AND CHIEF EXECUTIVE OFFICER


If the costs of a new intervention far exceed the benefits, or if patients cannot get access, we’ve failed – as a system – to provide value. Conversely, when we see benefits that far outstrip costs, we can be confident that we are moving the health system in a direction to higher value, with better health and lower costs.

Understanding that balance has never been more critical. The United States spends $3.3 trillion on health care every year, or 18 percent of the nation’s gross domestic product (GDP). That’s about equal to the entire GDP of Germany. Among the primary drivers of this spending are hospital care (32 percent); physician and clinical services (20 percent); retail prescription drugs (10 percent); and other health, residential, and personal care services (5 percent). We have a responsibility to make sure that those dollars are spent wisely and to define what we – as a company and as a part of the health care system – believe is a good investment in the health of the nation.

Celgene’s Value and Innovation Framework Report is an effort to help meet that responsibility. We have developed a framework that outlines our approach to value and defines our role as a driver of value.

 “We have a responsibility to define what we believe is a good investment in the health of the nation.”

Though spending on biopharmaceutical products remains a relatively small piece of the overall health care environment, the biopharmaceutical sector has had an outsized impact on outcomes, and we are proud of our role in a therapeutic revolution that has cut the cancer death rate by 25 percent since 1991. While overall spending on biopharmaceutical products has indeed increased over the years, it has contributed to significant improvements in health outcomes. In fact, one study found that over 70 percent of recent life expectancy growth is due to the increased use of medicines.

Even with the increasing innovation coming from the biopharmaceutical sector, there are signs that drug spending is stabilizing. In 2017, per-person spending on prescription drugs rose just 1.5 percent across plans covering employees and their families, less than half of the increase reported in 2016 and the lowest increase in 24 years of tracking drug-trend data. Another study found that after accounting for rebates and discounts, spending growth on prescription drugs in the United States slowed to 0.6 percent in 2017.

But we cannot simply proclaim successes, declare that we have provided value, and avoid further discussion. Instead, we must start with a clear definition of our goals and a fair-minded examination of our impact at every level of the health care system. This report is evidence of our commitment to evaluating our performance as “value drivers” so that we can continually refine our role in the virtuous cycle of innovation.

To learn more about how Celgene defines value and measures it through medical innovation, read the 2018 Value and Innovation Framework Report.

CHRISTINE FILLMORE BRAINSON, PHD, ASSISTANT PROFESSOR AT UNIVERSITY OF KENTUCKY MARKEY CANCER CENTER, EXPLAINS THE IMPLICATIONS OF RECENT DISCOVERIES IN NON-SMALL CELL LUNG CANCER SUBTYPES.

CHRISTINE FILLMORE BRAINSON, PHD, ASSISTANT PROFESSOR AT UNIVERSITY OF KENTUCKY MARKEY CANCER CENTER, EXPLAINS THE IMPLICATIONS OF RECENT DISCOVERIES IN NON-SMALL CELL LUNG CANCER SUBTYPES.

The two major types of non-small cell lung cancer (NSCLC), adenocarcinomas and squamous cell carcinomas, have long been considered two distinct diseases. But researchers are now discovering that these tumor types may have a much more complicated, intertwined relationship.

As researchers gather for the 2018 American Society of Clinical Oncology meeting, we reviewed the implications of these discoveries for the future of lung cancer treatment with Christine Fillmore Brainson, PhD, assistant professor at the University of Kentucky Markey Cancer Center.

What are some of the unanswered questions that continue to drive research in NSCLC?

We still don’t know which cells are the culprits — the “cells of origin” for different subtypes of lung cancer. That’s something our lab is trying to parse out in mouse models. Understanding the cells of origin may help us to develop treatments that specifically target these NSCLC subtypes.

We’re also trying to personalize treatment for lung cancer patients. At the University of Kentucky, when lung cancer patients don’t respond to chemotherapy, we sequence their tumor biopsy. This lets us understand the unique genetic combinations that contribute to their lung cancer. Then we consider the approved and investigational therapies that target those mutations.

How has our understanding of different types of lung cancer evolved recently?

We’re beginning to understand that there may be more plasticity in NSCLC subtypes than we had thought. Sometimes, a patient is originally diagnosed with adenocarcinoma. Then a second biopsy after treatment may reveal that those tumors have qualities of both adenocarcinoma and squamous cell carcinomas. Having a tumor that looks like both, which we call adenosquamous lung cancer, complicates things, and it has a poor prognosis. This transformation could be a factor in resistance to therapy in NSCLC.

Non-small Cell Lung Cancer Subtypes

Do we know what drives this change in the tumor cells?

We typically only see second biopsies after a patient has been treated with epidermal growth factor receptor (EGFR) kinase inhibitors. So that treatment might be driving the transformation in patients. Or it might also happen after chemotherapy. We don’t know because we don’t take that second biopsy then to look at it.

In a previous study, we showed that we could force this transition in mice through specific genetic changes.

How might this finding affect how doctors diagnose patients?

In the future, a diagnosis of adenosquamous lung cancer, rather than just adenocarcinomas or squamous cell carcinomas, might be common. And it might justify taking a second biopsy after chemotherapy. Right now, that’s not recommended, because often the patient isn’t doing well at that point, and you don’t want to add a lung surgery unless there will be a clear benefit.

Understanding the cells of origin may help us to develop treatments that specifically target these NSCLC subtypes.

If one NSCLC subtype can change into another, how could that affect treatment?

We’ve seen that targeted immunotherapies work well in squamous cell carcinoma. My laboratory is studying whether the transition to squamous cell carcinoma can make the patient’s cancer more susceptible to immunotherapy. We’re studying this in a mouse model right now. If we can push the transition toward squamous cell carcinoma with a targeted therapy, maybe we can boost the response to immunotherapy.

What does the future of lung cancer treatment look like?

Cytotoxic therapy, such as chemotherapy, and immunotherapy combinations are potentially going to be the future of NSCLC treatment. At ASCO, researchers will present studies that show more data on chemotherapy and immunotherapy combinations to treat adenocarcinomas. Combinations are being tested in clinical trials, and the Food and Drug Administration have approved a few combinations for specific circumstances. We see that some patients do much better when treated with immunotherapy and chemotherapy. So we should continue exploring combinations of immunotherapies with our standard therapies. Combinations seem to be one clear way to go forward.

To learn more about how immunotherapies may be a new partner for chemotherapy, read “The Evolving Role of Chemotherapy in Lung Cancer.”

Pancreatic cancer is once again an area of focus at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. New research is increasingly important as estimates show that the mortality rate of pancreatic cancer could surpass that of breast and colorectal cancers by 2030 in some countries. Celgene is at the forefront of the fight against pancreatic cancer, and at this year’s ASCO conference, new data will continue to expand our understanding of emerging investigational treatments.

Celgene continues the fight against pancreatic cancer through our commitment in advancing research, our collaboration with advocacy groups and our support to patients.

Some look. We envision.

Celgene is committed to advancing research to help change the lives of patients with pancreatic cancer. In 2017, more than 20 percent of our revenue was reinvested into R&D, one of the highest rates in the industry.

Part of our research aims to inform today’s treatment choices in pancreatic cancer. Given the availability of more treatment options for patients with metastatic pancreatic adenocarcinoma, it is time to develop a treatment plan for patients. Celgene is contributing to this important discussion by helping physicians and patients make informed treatment decisions. With an eye toward the future, we are also conducting research and collaborating with researchers around the world on 91 ongoing investigational trials that combine novel agents with the foundation of approved Celgene therapies. These trials involve more than 40 unique novel compounds across more than 30 mechanisms of action and target enrollment of more than 4,500 pancreas cancer patients.

Celgene: Your partner in the fight against pancreatic cancer.

Some hear. We listen.

Celgene collaborates with patient advocacy groups to bring hope to the fight against pancreatic cancer. In partnership with 29 international patient groups, Celgene created the first-ever World Pancreatic Cancer Day in 2014 and continues to grow the event. Celgene also supports events such as Purple Stride Walks in the United States, the European Multi-Stakeholder platform on Pancreatic Cancer in November 2014, 2015 Pancreatic Cancer Forum in Milan and grants to help transport patients to their treatment appointments through the CancerCare GetYouThere program.

Some touch. We feel.

Celgene is dedicated to offering compassion and support to patients with pancreatic cancer and those who care for them. To help them, Celgene developed NavigatePanc.com, a personal pancreatic cancer information center. The site provides information about the disease, clinical trials, support groups, finances and communication and allows patients and caregivers to create their own online libraries of relevant information. Celgene also recognizes that pancreatic cancer patients often have special nutritional needs due to compromised pancreatic function. Our response: a source for recipes and meal planning. Lastly, we are committed to increasing the awareness of pancreatic cancer in the healthcare community.

Pancreatic Cancer: Cooking. Comfort. Care.

We support all who fight pancreatic cancer.

Celgene is committed to providing information and support to people with pancreatic cancer, and their loved ones, to help them in making informed decisions throughout their journey.

To learn more:

Last year, chimeric antigen receptor (CAR) T cell therapy was recognized as the Advance of the Year in the American Society of Clinical Oncology (ASCO) Annual Report for its demonstrated benefits in certain blood cancers and its potential in many other tumor types. At this year’s ASCO annual meeting, the interest in CAR T cell therapy remains strong with the availability of more data for approved and investigational therapies.

“So far, the oncology community has greeted CAR T cell therapy with extraordinary enthusiasm,” said Dr. Jeremy Abramson, clinical director for the Center for Lymphoma at Massachusetts General Hospital. “We’ve had few effective treatment options for difficult-to-treat blood cancers like diffuse large B-cell lymphoma [DLBCL]. The newest data from ASCO continues to suggest that CAR T cell therapy may represent an important advance for some patients.”

DR. JEREMY ABRAMSON FROM MASSACHUSETTS GENERAL HOSPITAL BELIEVES THAT MANY QUESTIONS ABOUT CAR T CELL THERAPIES WILL BE ADDRESSED AT THIS YEAR’S ASCO ANNUAL MEETING.

DR. JEREMY ABRAMSON FROM MASSACHUSETTS GENERAL HOSPITAL BELIEVES THAT MANY QUESTIONS ABOUT CAR T CELL THERAPIES WILL BE ADDRESSED AT THIS YEAR’S ASCO ANNUAL MEETING.

A Long Time in the Making

The first investigational CAR T cells were developed over 30 years ago, using genetic engineering advances with the goal to reprogram a patient’s immune system to recognize and attack cancer cells. Early attempts were lackluster; the engineered T cells were slow to reproduce, died quickly and produced weak immune responses that weren’t effective at killing tumor cells.

Advances in genetic engineering tools and techniques, as well as a far better understanding of the human genome, have advanced this type of technology. Over the past five years, the number of clinical trials involving CAR T cell therapies has skyrocketed from just a handful to more than 180.

In 2017, the U.S. Food and Drug Administration approved the first two CAR T cell therapies — one for children with relapsed or refractory acute lymphoblastic leukemia and another for non-Hodgkin lymphoma in adults who have failed at least two other kinds of treatment.

These are just two examples of diseases for which CAR T cell therapy represents a radically different therapeutic approach.

“CAR T cells are specifically engineered to recognize, go after and attack the cancer cells,” Abramson said.

How CAR T Cell Therapy Works

CAR T CELL THERAPY BEGINS BY REMOVING A PATIENT’S T CELLS, WHICH FIGHT INFECTIONS IN THE BODY, THROUGH A BLOOD DRAW. THOSE CELLS ARE THEN SENT TO A MANUFACTURING SITE WHERE THEY ARE GENETICALLY ENGINEERED TO RECOGNIZE AND ATTACH TO ANTIGENS EXPRESSED ON CANCER CELLS AND SOME NORMAL CELLS. PATIENTS THEN RECEIVE CHEMOTHERAPY BEFORE THESE PROGRAMMED CELLS ARE RETURNED TO THEIR BODIES TO SEEK AND ATTACK CANCER CELLS. PATIENTS ARE MONITORED FOR SIDE EFFECTS AFTER CAR T CELL THERAPY.

Exploring Questions in Blood Cancers

While the first two CAR T therapies have been approved, Abramson notes that many questions remain, including CAR T cell therapy production, safety and longevity.

Scientists are still fine-tuning the process of creating CAR T cell therapies. For instance, studies continue around different ratios of two subtypes of T cells—CD4+ and CD8+ T cells— that may behave differently. That’s because CD8+ T cells have a cancer-killing effect, while CD4+ T cells produce chemical messages that boost T cell production. Finding the right ratio of CAR T cells created from these subtypes may impact the efficacy and safety of these treatments, according to Abramson. But the clinical significance of CD4:CD8 ratio remains unknown.

“Even the most effective therapies can only be administered if the toxicities can be identified and successfully treated and reversed,” Abramson explained. “We’re continuing to learn about potential toxicities with the different approved and investigational CAR T cell therapies, and how to optimally manage and prevent them.”

We are studying ways to make these therapies work better, designing more effective CAR T cells that may target different or multiple cancer proteins and combining them with other medications.

Adverse events that have been noted in trials of CAR T cell therapy include cytokine release syndrome (CRS) and neurotoxicity. CRS symptoms include fever, nausea, or headaches, and neurotoxicity symptoms include delirium, headaches and problems speaking. ASCO attendees will get a better understanding of the severity and timing of these and other potential safety issues as well as insight into paths for their prevention and treatment.

As for the durability of CAR T cell therapies, Abramson believes there’s work to be done.

“Less than half of patients with DLBCL who receive CAR T cell therapy are still in remission a year later,” he said. “We are studying ways to design more effective CAR T cells that may target different or multiple cancer proteins and learn how to combine them with other medications like checkpoint inhibitors or immunomodulators to see if we can enhance CAR T cell activity.”

Beyond the Blood

So far, CAR T cell therapies have only been approved for the treatment of blood cancers. The major challenge in solid tumors, such as lung and breast cancers, has been identifying a target that’s restricted to the tumor, so the CAR T cells don’t also attack the patient’s healthy cells.

CAR T cells kill healthy immune cells called B lymphocytes, for instance, as well as lymphoma cells, but patients can often do without those particular cells. But a treatment that attacked an entire organ — or organs — would have catastrophic effects.

According to Abramson, one potential way to get around the problem may be to create CAR T cells that attack only when they encounter a specific combination of targets. While a single protein might be shared by cancer and healthy cells, researchers are searching for patterns of multiple targets only found on cancer cells. Whether or not this tactic succeeds, Abramson is optimistic that scientists can find a way.

To learn more about the advances that will be discussed at ASCO 2018, read “ASCO 2018 Preview: Precision Medicine, CAR T Cells and Immunomodulators.”

Dr. Abramson is a lead principal investigator for Juno and has consultant/advisory roles with Celgene.

The cost and value of medical innovation in oncology is one of the hot topics on the agenda for this year’s American Society for Clinical Oncology Annual Meeting (ASCO). One cancer that has seen an increase in relative survival rates over the past decade is multiple myeloma. So it makes sense that multiple myeloma is at the center of a debate at ASCO on the cost and value of new therapies.

As one of the participants in that debate, Dr. Rafael Fonseca, a hematologist, oncologist and chair of the Department of Internal Medicine at Mayo Clinic in Arizona, will argue that society can’t afford not to provide patients with multiple myeloma access to the best care possible. In this Q&A, Fonseca shares his views about the affordability of cancer therapies, why many doctors hold onto the notion that medications are too expensive and the implications for future multiple myeloma treatment.

DR. RAFAEL FONSECA FROM THE MAYO CLINIC IN ARIZONA BELIEVES THAT SOCIETY CAN’T AFFORD NOT TO PROVIDE PATIENTS WITH MULTIPLE MYELOMA ACCESS TO THE BEST CARE POSSIBLE.

DR. RAFAEL FONSECA FROM THE MAYO CLINIC IN ARIZONA BELIEVES THAT SOCIETY CAN’T AFFORD NOT TO PROVIDE PATIENTS WITH MULTIPLE MYELOMA ACCESS TO THE BEST CARE POSSIBLE.

In the debate, you will argue that we can’t afford not to provide patients with access to the right treatment for them. How did you come to that conclusion?

“Over the past decade, I’ve witnessed so many patients with multiple myeloma increasingly beating the odds for survival. So I wanted to know what exactly was responsible for this. After some research, I concluded—as many of my colleagues have also—that it was the new medications. These innovative therapies provide tremendous value to our patients and society.”

When you discuss this topic with your fellow oncologists, what is the most compelling evidence supporting your position?

“I usually take a stepped approach to presenting my point of view. I ask them to consider the progress that we’ve made in survival in cancers like multiple myeloma and what they have seen in their own patients. I help them understand the value by walking them through all the new therapies that those improvements are attributed to. You can’t just look at the price tag of a specific medication, which they often focus on most.”

The opposing position is that patients and society cannot afford multiple myeloma therapies. Why don’t you believe that argument?

“The data don’t support the argument. One study found that 98 percent of patients paid $50 or less to fill their prescriptions in 2017. While that could be a hardship for some people, it is far different than the list prices of thousands of dollars that make headlines. So we need to talk about what patients are paying in the real world and what’s best for our patients.”

“Beyond that, there are the ethical considerations. Doctors should prescribe the medications they believe will benefit their patients the most.”

Why do doctors continue to say that new cancer therapies are unaffordable if the data suggest they aren’t for most patients?

“I feel like most cancer doctors are concerned about the cost of prescription medications out of their sense of compassion and responsibility for their patients. They see their role as treating patients responsibly. Prescribing a therapy that may cost them thousands seems inconsistent with that mission.”

“But they are so busy caring for patients that they don’t have the time to research the real world data about what patients actually pay for their prescriptions. As we see in other areas of discourse, facts matter. I believe that misunderstood empathy and baseless rhetoric can have real-world consequences for patients.”

Everyone agrees that today’s cancer treatments are simply not good enough and that innovation is key to improving cancer care.

Have you ever had a patient —or many—who could not access treatments that you prescribed?

“I cannot think of a single patient who could not access a medication due to financial reasons. I’ve had patients who have chosen other treatment options but for other reasons—never financial. In a few instances, we have had to go above and beyond to get them financial help from the manufacturer or non-profit groups. But those cases are the exceptions, not the rule.”

What do those on the other side suggest should be done about the affordability of multiple myeloma care and what are the potential consequences?

“When we say that new therapies are too expensive, what we’re doing is calling for price regulations. But without a doubt in my mind, those regulations will kill innovation. Medical innovation is a high-risk, high-reward endeavor. We should not fool ourselves into thinking that there won’t be consequences; we’ll have fewer new treatments for our patients as a result.”

Is there common ground in this debate over the value of multiple myeloma care that can be used to move forward?

“There is plenty of common ground. I think today’s cancer treatments are simply not good enough and that innovation is key to improving cancer care. So we should make sure that we do not hinder that innovation.”

“Most cancer doctors also agree that clinical trials should be as fast as possible without sacrificing safety, so they cost less and lead to faster approvals. And I think that we all think patients should have access to the best treatment options but have different ideas on how to provide that access.”

To learn more about the how medical innovation has improved the treatment of multiple myeloma, read “A Decade of Progress in Multiple Myeloma, and More to Come.”

Dr. Fonseca has received speaker fees, advisory board fees, travel support in connection with consulting services, and research support from Celgene.

Last year, Americans took more prescription medicines than ever before due in part to efforts to improve adherence. In addition, the number of new medications approved more than doubled from 2016. But if you think the country is paying substantially more at the pharmacy as a result, you may be surprised.

Prescription medication spending increased just 0.6 percent last year, less than the rate of inflation and the lowest growth rate since 2012, according to a report published by the IQVIA Institute for Human Data Science. Murray Aitken, executive director of the IQVIA Institute, explains why prescription spending growth has remained in check, why growth in prescription spending isn’t necessarily a bad thing and what we can expect in the near future.

MURRAY AITKEN, EXECUTIVE DIRECTOR OF THE IQVIA INSTITUTE, BELIEVES HIGH GROWTH IN PRESCRIPTION SPENDING CAN REPRESENT GOOD VALUE IN TERMS OF LONGER, HEALTHIER LIVES.

MURRAY AITKEN, EXECUTIVE DIRECTOR OF THE IQVIA INSTITUTE, BELIEVES HIGH GROWTH IN PRESCRIPTION SPENDING CAN REPRESENT GOOD VALUE IN TERMS OF LONGER, HEALTHIER LIVES.

Why was the growth rate for prescription medication spending just 0.6 percent in 2017?

“That relatively low rate is due to patent expirations and lower cost generics, which are offsetting the growth from new therapies and price increases. In fact, a record-setting 1,027 generic medications were approved in 2017. If we look at retail and mail-order prescriptions, spending actually declined 2.1 percent last year, as we had more new injectable and infusible treatments than oral treatments last year. The prescription spending growth rate in 2017 is significantly lower than the 9 to 10 percent that we saw in 2014 and 2015, which were historically high levels of growth.”

What happened in 2014 and 2015 that caused those high rates of growth in prescription spending?

“Between 2014 and 2015, we saw the rise and fall of hepatitis C spending, as therapies that cured a significant number of patients were introduced. Since that wave of innovation, spending has grown more slowly.

“When innovative therapies are introduced that address an unmet need for many patients, spending will go up as we saw in hepatitis C. That is not a bad thing. That growth is supported by the value that innovative therapies provide in the form of longer and better lives. When we get an effective therapy for Alzheimer’s, for instance, we will see spending increase as we treat the millions of Americans to improve their lives and reduce other healthcare costs of caring for those with the disease.”

Prescription Drug Spending Increased Just 0.6% in 2017

How are the prescription spending growth rates in your report different from those that we see elsewhere?

“First, we are not basing our analysis on list price. We are looking at the revenue manufacturers receive after all the rebates, discounts, coupons and vouchers have been accounted for. Secondly, we are reporting on the total use of all medicines through all distribution channels, not just individual medications. Individual medication costs tend to make headlines but aren’t necessarily reflective of the overall market.”

Are patients paying more for prescription medications because of price increases?

“Over the past five years, patient out-of-pocket costs have actually declined by 15 percent to $8.69 per prescription on average in 2017. These lower out-of-pocket costs are due to higher usage of generics and manufacturers’ coupons.

“But patients’ out-of-pocket costs remain high for a small number of prescriptions. Patients paid more than $500 for about 0.2 percent of all prescriptions in 2017. These patients are usually those in the coverage gap of Medicare plans or the deductible phase of their insurance plans. They may get the same medicine for less at a different time of year.”

Patient Out-of-Pocket Costs Down 15% Since 2013

What is the outlook for prescription spending and patient costs over the next few years?

“While there are many uncertainties, including government policy, we don’t foresee any major disruptions over the next five years. So we’re forecasting spending growth to average between 2 and 5 percent per year. Growth will continue to be driven by innovation in various disease areas, but especially in oncology. That growth will continue to be offset by expirations of patents, which are designed to keep spending in check over the long term.”

To learn how medical innovation saves lives and has reduced health expenditures, read “When It Comes to Healthcare Costs, New Medicines Are the Solution, Not the Problem.”

An estimated 1.5 million Americans are affected by lupus, and each of these patients has a different story to tell. This inflammatory disease — in which a patient’s immune system begins attacking healthy organs and cells — has many different symptoms and affects each person differently. Some people with lupus have a few mild symptoms, but others can experience many symptoms and severe complications.

In this video produced for this year’s Lupus Awareness Month (May), we asked several patients to share how this complicated, incurable disease affects their daily lives, what they want others to know about their condition, and how they have learned to manage their symptoms.

Celgene wants to thank the Lupus Research Alliance for their partnership in the making of the video.

To learn more about how advances in lupus research are leading to potential new treatment options, read “Genetic Research in Lupus Offers New Lines of Attack.”

For decades, researchers seeking to develop new treatment options for multiple sclerosis (MS) believed that it was primarily a disease of the brain’s white matter, but recent studies have highlighted that grey matter plays an important role as well. For instance, grey matter loss, known as atrophy, may be seen in early stages of the disease and is associated with worsening symptoms.

As part of this year’s efforts to raise awareness of the disease during World MS Day on May 30, Dr. Robert Zivadinov, professor of Neurology and director of the Buffalo Neuroimaging Analysis Center and Center for Biomedical Imaging at Clinical Translational Science Institute at the University of Buffalo, explains researchers’ evolving understanding of the role of grey matter damage in MS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

DR. ROBERT ZIVADINOV FROM THE UNIVERSITY OF BUFFALO BELIEVES UNRAVELING THE ROLE OF GREY MATTER IN MULTIPLE SCLEROSIS MAY HAVE IMPLICATIONS FOR FUTURE TREATMENTS.

MS was previously considered to affect white matter primarily. How has that understanding evolved to include grey matter?

“About 15 years ago, improved imaging techniques revealed that large areas of grey matter were affected in patients. This evidence helped explain why some patients had such severe disease but relatively few damaged areas in the white matter, known as lesions.”

Are there specific regions of grey matter that are affected by MS?

“Not all parts of the grey matter are equally affected. There’s definitely significant involvement of the cortical layers of the brain’s grey matter, which is linked to symptoms such as fatigue, cognitive changes and memory loss.

“The deep grey matter is also involved in MS as well, and in particular the thalamus, which relays motor signals and regulates things like consciousness, sleep and alertness.”

“Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter.”

What do researchers know about the connection between the loss of grey matter, cognitive dysfunction, disability and MS progression?

“Many studies have found links between grey matter damage with both physical and cognitive impairment in patients with MS, including symptoms such as muscle control, sensory perception and memory. Some studies have found that grey matter atrophy correlates with disability, cognitive impairment and disease progression better than white matter lesions do.

“Studies also suggest that grey matter lesions occur rather early on, particularly in relapsing-remitting MS, even before white matter lesions appear. It could very well be a potential marker for predicting disease progression.”

What is preventing it from becoming a more useful predictor of disease progression?

“Grey matter lesions are less pronounced than white brain lesions, so doctors have difficulty seeing them on typical MRIs. Instead, we have to use advanced, highly sensitive MRI techniques to measure changes in grey matter, but those techniques aren’t available everywhere. They require specialized equipment and expertise that is typically only found in academic research centers. That is one reason why grey matter atrophy has had limited use in the clinic.”

What do we still not understand about grey matter atrophy in people with MS?

“We still don’t understand what causes the damage. Grey matter atrophy is associated with several genetic, viral and environmental risk factors, but we haven’t pinpointed the mechanisms yet.”

What can be done to reduce the risk of damage to grey matter?

“That’s the holy grail. Most MS trials weren’t necessarily designed to answer that question. We are going to have to change the design of MS trials. Instead of only using MRIs of white matter lesions as an endpoint, we’ll need more sensitive imaging techniques to monitor grey matter changes over time as well.”

To learn more about how MS affects the brain over a lifetime, read “How Multiple Sclerosis Affects the Brain and CNS.”

Dr. Robert Zivadinov is a paid consultant for Celgene.

In 2017, California’s state health insurance exchange became the first to implement caps on what insurers could charge patients for a prescription medication, topping them at $250 per month, in an effort to protect the chronically ill from ever-increasing insurance cost sharing. While some critics argued that caps would substantially increase pharmacy spending and premiums for everyone, several studies suggested otherwise.

GABRIELA DIEGUEZ, A PRINCIPAL AND CONSULTING ACTUARY WITH MILLIMAN, DID NOT SEE CALIFORNIA INSURERS EXPECTING MUCH IMPACT ON SPENDING OR PREMIUMS FROM COST-SHARING CAPS.

GABRIELA DIEGUEZ, A PRINCIPAL AND CONSULTING ACTUARY WITH MILLIMAN, DID NOT SEE CALIFORNIA INSURERS EXPECTING MUCH IMPACT ON SPENDING OR PREMIUMS FROM COST-SHARING CAPS.

Now, California’s insurers have released their cost projections for 2017, the year that the cost-sharing caps went into effect. The data reveal that insurers did not project much, if any, change in spending or premiums due to the patient out-of-pocket caps, according to an analysis by the actuarial firm Milliman.

“If insurers thought that the sky was falling, we would have seen it in their projections,” said Gabriela Dieguez, a principal and consulting actuary with Milliman and the lead author of the report. “But they didn’t seem to be anticipating spending to grow disproportionately.”

Dieguez and colleagues compared the change in pharmacy spending projections from insurers in California to those in other states without caps. Not only did California insurers not project higher prescription spending increases between 2015 and 2017 than did other states, but their projections actually came in about 1 percent lower for people who buy their own insurance and 3 percent lower for those who get their insurance through a small employer.

Cost Sharing Caps

Some have worried that insurers might raise premiums substantially to guard against any losses from the caps. But this doesn’t seem to be the case, according to the Milliman analysis, which estimated that premiums increased by only about 1 percent for average members.

That relatively small increase leads to significant savings when an innovative therapy for a chronic disease is needed. Dieguez and colleagues projected annual savings of $586 per family member for families that include someone with blood cancer and $683 per family member for those including someone with rheumatoid arthritis.

Savings Due To Cost-Sharing Caps

The findings will help California and other states who have passed similar legislation understand the impact of their caps. Delaware, Louisiana, Maine, Maryland, Montana, New York and Vermont have all limited how much insurers can ask patients to pay for their prescription medications.

“While several states have regulations that limit cost sharing for prescription medications, we chose California because its large insured population provided a credible basis for our analysis,” Dieguez said.

If insurers thought that the sky was falling, we would have seen it in their projections. But they don’t seem to be anticipating spending to grow disproportionately.

The analysis will also inform states who are looking to introduce such legislation, including Connecticut, Illinois, Kansas, Kentucky, Massachusetts, Michigan, Mississippi, Nevada, New Jersey, Ohio, Oregon, Pennsylvania and Washington.

While these numbers are based on projections from insurers, the true impact of the caps on prescription spending and premiums will be revealed when California’s insurers release the final data for 2017 later this year.

“We’re very much looking forward to those data so we can see if the caps made as small of an impact on spending and premiums as the insurers projected,” Dieguez said. “Many people are following the California case closely.”

To learn more about how states are taking action to improve patient access, read “Protecting Patients from Higher Cost Sharing.”

Last week, scientists, physicians and patient advocates gathered in Chicago for the 2018 American Society of Gene & Cell Therapy (ASGCT) annual meeting to discuss results of recent trials for cellular immunotherapies, including chimeric antigen receptor (CAR) T cell therapies. These treatments have the potential to change the treatment paradigm in oncology, but obstacles remain for cancer centers seeking to take advantage of this new approach.

In this Q&A, Dr. Helen Heslop, director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston Methodist Hospital and Texas Children’s Hospital, explains what was discussed at the meeting regarding the practical challenges cancer centers are facing when offering CAR T cell therapies to patients.

DR. HELEN HESLOP FROM BAYLOR COLLEGE OF MEDICINE EXPLAINS SOME OF THE CHALLENGES OF IMPLEMENTING CHIMERIC ANTIGEN RECEPTOR T CELL THERAPIES.

DR. HELEN HESLOP FROM BAYLOR COLLEGE OF MEDICINE EXPLAINS SOME OF THE CHALLENGES OF IMPLEMENTING CHIMERIC ANTIGEN RECEPTOR T CELL THERAPIES.

What types of centers are offering CAR T cell therapy?

“A variety of centers are setting up CAR T cell programs, including public and private, large and small, pediatric and adult cancer centers.

“Everyone is doing it slightly differently, so we need to share best practices regarding the practical nuts and bolts of implementation in three broad areas: setting up a program to offer CAR T cell therapies, what it takes to get accredited and issues with access and reimbursement.”

How is the administration of cellular immunotherapies different from traditional treatments?

“Giving a patient cell therapy is different than typical small molecules or biologics. The patient’s lymphocytes are separated from the rest of the patient’s blood cells and plasma in a process called apheresis. The lymphocytes are then sent to a central manufacturing to be genetically reengineered. The modified cells are then sent to the treating center as a frozen CAR T cell product. The product is then thawed and infused back into the patient.

“The cell collection process is more akin to a stem cell transplant, so centers that are currently performing stem cell transplants have most of the processes in place to offer CAR T cell therapies.”

And those processes would include?

“With cellular therapies, there is the risk of developing complications that require specialized management, such as cytokine release syndrome and neurotoxicity.”

About 40 centers in the United States are offering cellular immunotherapies. But that number could rise quickly.

How many centers are currently offering CAR T cell therapy?

“Right now, about 40 centers in the United States are offering cellular immunotherapies approved by the U.S. Food and Drug Administration to patients. But there are close to 200 transplant programs across the country, so that number could rise quickly if more centers attain Risk Evaluation and Mitigation Strategy certification per the individual product labels.”

What is the most significant challenge for centers in implementing these therapies?

“Aside from the clinical issues, the financial and administrative aspects and access to these new therapies for patients are also significant challenges. Hospitals have to create new processes for this new treatment paradigm and codes for the procedures involved with CAR T cell therapy administration are not yet available.”

What’s next for cellular immunotherapies?

“So far, CAR T cells have only been approved for specific relapsed or refractory diseases. One obvious question requiring careful investigation of risks and benefits is whether you can give CAR T cell therapy earlier in the course of therapy.”

To learn more about how CAR T cells may help immune cells identify cancer cells, read “Revealing Cancer Cells to the Immune System.”