A clinical study found immunotherapy treatment with the drug teplizumab postponed the onset of type 1 diabetes (T1D) among at-risk children and adults for an average of two years, and for one patient, 11 years and counting.

“Half the people in the study are way beyond two years,” says Yale University’s Dr. Kevan Herold, who has been working on a cure for T1D for 30 years. People with T1D have to manage the disease 24/7 or risk dangerously low or high blood sugar levels and long-term complications, said Herold, the clinical trial’s principal investigator.

Before participating in a clinical trial at age 9, Claire Wirt, now 16, had antibodies that put her at risk of developing T1D within two years. The Rochester, N.Y., girl has been free of T1D for seven years. While the two-week outpatient infusion treatment is not a cure or preventative, she said, “having seven years of my childhood without having to think about this is invaluable.”

Her mom, Dr. Cory Wirt, a pediatrician, has seen family members live with T1D. They have to check their blood sugar levels throughout the day and give themselves insulin, the hormone their body needs to turn food into energy.

“Every day without insulin is a gift,” said Wirt, who closed her private practice temporarily to spend two weeks in New Haven while her daughter received infusions via a needle each day at Yale. “I appreciate 84 months of not checking blood sugars multiple times per day, worrying about life-threatening lows. So far, I’ve been able to avoid all those mom things my relative had to suffer through as the mom of a type 1 diabetic. And we don’t have the expense of all these appointments, labs, insulin and supplies.”

Yale University’s Dr. Kevan Herold, who has T1D, was the clinical trial’s principal investigator.

For the past 20 years, TrialNet, an international network of scientists and physicians involved in T1D research, has collected data from more than 200,000 relatives of people with T1D. This led to identifying stages of T1D and who is likely to develop the autoimmune disease.

In the U.S., 64,000 new cases of type 1 diabetes are diagnosed annually, and non-Hispanic white people are more likely to develop T1D than Black and Hispanic people, according to JDRF, a nonprofit that funds TID research.

“It’s a historic milestone in the course of type 1 diabetes. For 100 years, we’ve put Band-Aids over type 1,” said Aaron Kowalski, CEO of JDRF. “It’s the first drug ever to treat the disease itself rather than the symptoms of the disease.” JDRF has funded Herold’s research since the 1990s, he said. Along the way, this treatment has gone through four pharmaceutical companies.

In anticipation of the FDA’s approval, T1D networks and podcasts have buzzed for months, said Susan Lybeck, research information volunteer for JDRF’s Greater Connecticut and Western Massachusetts chapter. “It’s big news.”

The antibodies for diabetes can be present for years, but clinical T1D isn’t detected until people develop symptoms, such as feeling tired and thirsty, urinating frequently and losing weight. Since 85% of type 1 diabetics have no family history of the disease, many people misread the signs and about half end up in diabetic ketoacidosis (DKA) a high blood sugar complication that can lead to hospitalization, coma and even death.

The approval of the new drug, teplizumab, follows a study published in 2019 in the New England Journal of Medicine. All 76 participants, relatives of a type 1 diabetic, had two or more antibodies for T1D, putting them at nearly 100% risk. The immunotherapy treatment, sold under the name Tzield, prevents the body’s immune system from attacking its insulin-producing beta cells. Tzield, made by Provention Bio in partnership with Sanofi to market the drug, will treat patients found in screening tests to have precursory signs of T1D.

Since the TrialNet clinical trial was a quadruple-blind, placebo-controlled study, the patients, doctors, researchers and outcomes assessors didn’t know which patients received the treatment drug and which got a placebo. When Herold heard the study results, “I was thrilled. I can’t tell you the terror when you have the Zoom call,” he said. “In this one Zoom call, my whole career could be trashed.” One patient told him this may influence her decision to have children, he said.

Herold had led an earlier study giving teplizumab to those newly diagnosed with T1D, and, in 45% of cases, it preserved patients’ ability to make more of their own insulin for at least two years after treatment than those in the control group who didn’t receive treatment.

Hanna Rosenfield and her mother, Amy.

Hanna Rosenfield, who participated in that clinical trial within six weeks of her diagnosis in 2008, kept producing insulin for eight years after being diagnosed at age 10, said her mother, Amy Rosenfield, of Farmington.  The T1D study participants still had to monitor their blood sugar levels and give themselves insulin, but less than those not receiving the treatment; eventually, their bodies stopped making insulin.

Despite the past decade’s treatment advances, nothing had worked to prevent diabetes. “This is the first approval of a drug to prevent autoimmune disease,” said Herold, who has T1D. Researchers are already building on this discovery, he said, and expect advances like those seen in immunotherapy for cancer patients.

The treatment, approved for those ages 8 and up, would cost $193,900, according to Provention Bio, and it’s expected to be available by year’s end, according to a company spokesperson. JDRF is committed to working with the drug company, health plans and others to ensure treatment is affordable, a JDRF statement said. With insurance coverage and its patient support program, Provention Bio has said people with commercial or private insurance may pay as little as $0 for Tzield, the JDRF statement said. JDRF offers information about patient assistance programs through its website’s Health Insurance Guide.  Those with HUSKY health insurance will be eligible to receive coverage if the manufacturer enters into a federal rebate agreement with the Centers for Medicare and Medicaid Services, according to a state Department of Social Services spokesperson.

Meanwhile, Herold, JDRF and other advocates hope the availability of treatment will propel screening for T1D markers in children between 3 and 5 years, since that’s when most antibodies appear. While T1D is a genetic disease, 85% of newly diagnosed patients have no family history. As a result, increased thirst and fatigue are attributed to flu, food poisoning or other illness, delaying diagnosis.

Before the pandemic, newly diagnosed type 1 diabetics faced a 40% risk of DKA; during the pandemic, the risk rose to 50%. People screened for markers through TrialNet face less than a 5% risk of DKA, Kowalski said. “DKA kills people. It’s completely preventable,” Kowalski said. “Screening is critical.”

Since 2003, drug costs in Connecticut have increased faster than prices across the nation, reports the nonprofit Connecticut Health Policy Project. The advocacy group also found that Connecticut residents spend more per person on prescriptions than residents in all states except Delaware and that rate is rising much faster than in other states.

According to the State Comptroller’s Office, the total net costs of prescription drugs in the state employee health plan rose 29 percent, from $257.6 million in 2014 to $332.3 million in 2017, with diabetes drugs the most expensive therapeutic class.

Some of the companies to hike prices on dozens of medications by more than 9 percent this year include Allergan Plc, Insys Therapeutics Inc., Horizon Pharma Ltd., and Teva Ltd, according to Jefferies LLC, a New York-based investment advisory firm.

“Shame does not work. Competition does not work. What’s left? Governments saying what they’re going to pay for the drug,” said Jill Zorn, a senior policy officer at the advocacy organization Universal Health Care Foundation of Connecticut. “The states are acting because the federal government isn’t.”

Connecticut and other states are stepping in to control costs. Earlier this year, the Connecticut State Healthcare Cabinet recommended, among other measures, the creation of a Drug Review Board authorized to investigate drug manufacturers’ pricing. The cabinet also called for transparency in business practices and for consumers to be charged an amount based on the negotiated price of a drug.

Maryland last year passed legislation that prohibits price gouging on essential off-patent or generic drugs. Also last year, California approved legislation requiring drug makers to provide a 60-day notice if they raise prices by more than 16 percent in two years. Nevada was first among states to pass an insulin drug pricing transparency bill.

Pharma companies are quick to note that most net price increases have been modest. “For Pfizer’s U.S. biopharma business, as of the third quarter of 2017, the weighted average net selling price increase year to date was 3 percent,” said Sally Beatty, a Pfizer Inc. spokesperson.

But Piyush Bansal, a senior analyst with Frost & Sullivan, points out that Pfizer, which maintains a large R&D facility in Groton, hiked U.S. prices for 91 drugs by an average of 20 percent in 2017. And for Big Pharma, price increases have outpaced the demand. “Maintaining profit margin was the key driver behind price increase rather than demand-supply,” Bansal said.

Legislators say they hear complaints from constituents about drug costs weekly. “Drug prices are way too high, and there are laws on the books that protect drug companies,” U.S. Senator Chris Murphy said. “I want to change those laws, to stop drug companies from overcharging and to lower costs by allowing Medicare to negotiate directly with drug companies.”

Adding to patients’ woes, pharmaceutical companies have extended patent rights on blockbuster drugs to limit competition. For example, the patent for Humira from AbbVie Pharma expired in 2014. But the company filed multiple patents surrounding Humira, from dosage tweaks to delivery methods, avoiding competition from generic products.

Insurers, too, are driving patients to ration their medication. Dr. Prasad Panthagani, an ophthalmologist in Bloomfield, said elderly patients frequently accidentally spill a few drops of glaucoma medication, such as Alphagan or Travatan, when applying it to their eyes. “If the bottle finishes before 30 days, they run out of the medicine,” he said. “Patients forego dosages for the remaining period since the insurance company won’t pay. If there is no optimal control of intra-ocular pressure, patients could lose their eyesight.” Without insurance, a 5 ml, 30-day supply of Alphagan was priced at $208; Travatan at $440.

Nora Duncan, state director at the American Association of Retired Persons (AARP), said seniors are also affected by insurers switching plan formularies in the middle of the year. “HB 7123 is a good bill on trying to limit how much can change. There is a lot of opposition from the pharmaceutical lobby; but that information should stay consistent through the calendar year.”  The bill is before the legislature.

Carl Jordan Castro Photo.

Todd Gray, 54, standing in his cubicle at CPTV in Hartford. He has lived with diabetes for 20 years.

The Connecticut Health Policy Project data show that net pharmacy spending minus rebates from Connecticut’s Medicaid program tripled from 2000 to 2017. After rebates, Medicaid’s pharmacy costs decreased from $542 million in 2015 to $465 million in 2017, a drop of over 14 percent, said David Dearborn, spokesperson at the Connecticut Department of Social Services.

But for most consumers, prices cannot drop soon enough. Todd Gray’s troubles began when the deductible under his insurance plan shot up from $3,000 last year to $7,300 in 2018. Along with it, his blood sugar rose to more than 300 milligrams per deciliter as he experienced blurred vision and edginess, culminating in an “episode of yelling” at work. The 55-year-old diabetic had skipped his medication in January after sticker shock at the pharmacy.

“Walgreens said I had to pay $1,100 for one month’s supply of Humalog.” an injectable insulin, he said. “I didn’t have the money, so I didn’t buy it.” Humalog does not have a generic equivalent. A concerned colleague did some research and found Humalog online at Blink Health for $360. “I pre-pay and pick it up at Walmart,” said Gray, who also shells out $350 per month for Lantus, another diabetes drug without a generic alternative.

Part of the ire against Big Pharma is that the numbers simply don’t add up. For example, it costs just under $5 to produce a 10 ml vial of analog insulin, according to the Type 1 Diabetes Defense Fund. Eli Lilly’s launch price for Humalog in 1996 was $21, and subsequent competition from other insulin makers did not drive down the price. Instead, manufacturers began to increase prices in tandem and Humalog pharmacy price starts at $500, according to GoodRx website.

Despite the savings with Blink Health, Gray does not inject himself with Humalog three times a day as prescribed. “I do it once a day, or sometimes twice, so it can last longer.” His blood sugar is still not controlled.

“This year was tough,” he said. “Next year will be catastrophic if things don’t change.”

The doctors say that the out-of-pocket costs for insulin, ranging from $25 to upwards of $600 a month, depending on insurance coverage, are forcing many of their low-income patients to choose between treatment and paying their bills.

“Some of my patients have to make the choice between rent or insulin,” said Dr. Bismruta Misra, an endocrinologist with the Stamford Health Medical Group. “So they spread out taking insulin [injecting it less frequently than a doctor has prescribed] or don’t take it.”

Experts and recent studies point to drug companies’ long-standing patents and the lack of generic or “biosimilar” insulin as key reasons why the drug is so expensive.

A study by Philip Clarke, a professor of health economics at the University of Melbourne in Australia, reported that the price of insulin has tripled from 2002-2013. The findings were published in a research letter in the April 5 issue of the Journal of the American Medical Association.

Studies report that the cost of insulin has risen by triple-digit percentages.

In the United States. Just three pharmaceutical companies hold patents that allow them to manufacture insulin: Eli Lilly, Sanofi and Novo Nordisk. Put together, the three made more than $12 billion in profits in 2014, with insulin accounting for a large portion. All three hiked their prices in the last five years by 168 to 325 percent, says Dr. Kasia Lipska, an endocrinologist at the Yale School of Medicine.

A diabetic needing insulin but unable to buy it “ultimately will hit our emergency room,” said Dr. Cunegundo Vergara, who specializes in internal medicine at Hartford Hospital.

Vergara says “plenty” of low-income diabetics in the Hartford area are living without physician-prescribed insulin.

Similarly, in New Haven, Dr. Anne Camp, an endocrinologist at the Fair Haven Community Health Center, said she has seen “many patients referred to me because their diabetes is out of control, and the major reason is that they can’t afford their insulin. Many other patients are prescribed insulin, and they don’t return for a follow-up, because they are too embarrassed to admit they can’t afford it.”

About 257,000 Connecticut adults (8.9 percent) have been diagnosed with diabetes. Hispanics and African Americans are more than twice as likely to have the disease compared with whites and they are at greater risk of dying from diabetes-related causes, according to the latest data from state Department of Public Health. Diabetes was the seventh leading cause of death in Connecticut in 2013, killing 664 people.

The U.S. Centers for Disease Control and Prevention reports that the number of Americans diagnosed with diabetes increased from 5.5 million in 1980 to 22 million in 2014. Type 2 diabetes is the most common form.

The higher rates of Type 2 diabetes among African Americans and Hispanics “appear to be based on a number of factors, including [differences in] access to healthy foods, physical activity and genetics,” said Dana Marnane, a vice president for public relations at Greenwich Hospital. The hospital reported a 19.5 percent increase in patients discharged with diabetes as a primary or secondary diagnosis in fiscal year 2015, compared with 2014.

Diabetes is a disease in which blood sugar levels are higher than normal. Insulin keeps blood sugar from rising too high. Without insulin for an extended period of time, a diabetic increases the likelihood of heart attack, stroke or death.

Lipska, the Yale endocrinologist, criticized pharmacy benefit managers—who negotiate with drug companies on behalf of employer and government insurance programs—for being more focused on accepting rebates from drug manufacturers than on bargaining for lower drug prices.

To make insulin more affordable, Lipska said, more competition is needed among insulin manufacturers, and biosimilar products must be made available for patients in the United States. There also is a need for better pricing transparency and regulation, she said.

Eli Lilly spokeswoman Julie Williams said she could not disclose the average cost to manufacture, package and distribute insulin to each user, because manufacturing and distribution costs are proprietary. Eli Lilly introduced the world’s first commercial insulin in 1923.

A biosimilar product hasn’t emerged from other manufacturers, she said, “because developing and manufacturing insulin requires billions of dollars in investment, along with deep scientific and technical expertise.”

She said the reason people say insulin is expensive “are complex and go beyond the medicine’s list price,” Williams said. “One of the primary reasons is the advent of new insurance plan designs—particularly the increased use of high-deductible health plans, which shift more of the cost to the individual.”

Many low-income Americans get insulin through Medicaid, and in Connecticut Medicaid covers insulin and diabetes supplies at no cost. Lilly offers patient- assistance programs that provide free medicine for one year to low-income patients who meet specific financial qualifications. But Williams acknowledged, “Additional solutions are needed so all patients have access to their medicine.”

Novo Nordisk and Sanofi did not return calls seeking comment.

The American Diabetes Association, which represents 441,000 people, says that no diabetic should go without insulin because of “prohibitive costs or accessibility issues.”   The association says that “many parties, including pharmacy benefit managers, insurers and retailers are involved in the path of medications” from manufacturer to patient. The ADA advocates “transparency by all parties in their pricing policies and a continued dialogue” to develop lasting, affordable solutions.”

At the Fair Haven clinic, many patients turn to discount retailers, such as Wal-Mart, where a cheaper but older type of insulin is sold, Camp said. But many doctors won’t prescribe it because it often isn’t as effective in managing and treating diabetes, Camp said.

The retail cost for a month’s supply for a typical Fair Haven clinic patient who uses 100 units of insulin daily to treat Type 2 diabetes is about $600 to $800, Camp said. And diabetic patients commonly have other health problems, including high blood pressure and high cholesterol that also require medication and treatment.

“What person making $30,000 a year can lay down $600 a month for insulin?’’ asked Camp, whose clinic treats about 16,000 patients annually, 72 percent Hispanic, 20 percent African American and 80 percent below the federal poverty level.

About 25 percent of the clinic’s patients have no health insurance, and those with private insurance often have “enormous deductibles, such as $4,000 a year,” she said.

Fair Haven participates in the federal 340B program, which requires drug manufacturers to provide outpatient drugs to eligible health care organizations at significantly reduced prices.

“In this country,” Camp said, “we have the potential for really good diabetes treatment. Yet, sadly, because diabetes has become such a high-cost condition, many people can’t get access to it.”