Every morning, Marta Deike gets out of bed and drags herself to the kitchen.

It’s a slow process. Her legs are weak and feel too heavy to move. Standing is difficult. Her vision is blurred, and talking is a struggle.

When she finally makes it to her kitchen, she painstakingly pours a glass of seltzer — the bubbles help her to swallow — and takes a dose of her medication.

Within minutes, her muscles begin to function. Her vision clears, and holding up her head and moving her legs are no longer herculean tasks.

Deike, who lives on a small plot of land just outside Lodi, has Lambert-Eaton Myasthenic Syndrome, a rare autoimmune disease.

In those with LEMS, antibodies attack the areas where nerves and muscles connect, effectively muting signals to the muscles to move.

For years, Deike has been taking a medication called 3,4-DAP, which counteracts the symptoms of LEMS. With the medication, Deike is able to work as an assistant coach of Tokay High School’s cross country team. She also is able to grow her own vegetables and work with her animals.

“I feel like a contributing member of society,” she said.

Without the medication, she’s essentially bedridden. Every move requires an incredible amount of effort. Even breathing is difficult.

“I can’t lift anything,” she said. “I can’t walk anywhere.”

Until recently, this wasn’t a problem. Deike was one of the many LEMS patients who worked with the FDA Expanded Access Program and Jacobus Pharmaceuticals to get 3,4-DAP — short for 3,4-diaminopyridine. The program helps people with rare diseases get access to medications that can treat their symptoms, even if those medications do not have FDA approval, provided that there are no alternatives available.

But in November, Catalyst Pharmaceuticals received FDA approval for its version of the medication, Firdapse.

And unlike 3,4-DAP, which Jacobus was giving to patients for free or which could be purchased at a compounding pharmacy for a few hundred dollars a month, Firdapse comes with a hefty price tag — $375,000 per person, per year.

FDA approves Firdapse

On Nov. 28 of last year, the U.S. Food and Drug Administration announced the approval of Firdapse, the first approved treatment for LEMS.

“There has been a long-standing need for a treatment for this rare disorder,” said Dr. Billy Dunn, director of the Division of Neurology Products at the FDA Center for Drug Evaluation and Research.

According to a press release from the FDA in November, Catalyst conducted two clinical trials with 64 adult patients, who received either Firdapse or a placebo. In a December conference call with journalists, Catalyst said it had also spent tens of millions of dollars on 70 studies over the past nine years.

“After completing the comprehensive clinical and non-clinical development programs that were required for us to obtain FDA approval of Firdapse as a treatment for LEMS, we are gratified to finally be able to deliver a much-needed evidence-based therapy to all LEMS patients in the U.S.,” Catalyst CEO Patrick McEnany said during a Dec. 13 press conference call.

Firdapse is Catalyst’s version of 3,4-DAP, which was discovered in Scotland in the 1970s. By the 1980s, doctors in Sweden showed it might be useful in treating LEMS.

Jacobus Pharmaceuticals, based in New Jersey, began working with university physicians to produce 3,4-DAP for clinical trials in the early 1990s, at the request of the Muscular Dystrophy Association. However, the FDA approval process at the time was too expensive for the family-owned company to pursue, co-owner Laura Jacobus told NPR in 2015.

So instead, the company decided to continue providing the drug to university studies, as well as to work with doctors to provide it — free of charge, aside from shipping costs — to LEMS patients. The drug could also be specially ordered from compounding pharmacies at a low cost.

In France, the Hôpitaux de Paris hospital system began producing its own phosphate salt version, 3,4-DAPP, and licensed the intellectual property of that version to a French biopharmaceutical company. In 2009, that license was purchased by BioMarin and approved in Europe under the name Firdapse.

In 2010, the company raised the price of Firdapse, and faced criticism over the decision. The yearly price tag for 3,4-DAP in the UK cost between $1,280 and $3,200 in 2010; BioMarin’s Firdapse cost $64,000 a year.

In response to BioMarin’s release of Firdapse, a group of more than a dozen neurologists and patients’ rights advocates sent an open letter to the UK’s prime minister, printed in the journal BMJ on Nov. 17, 2010. In the letter, they called attention to an unintended consequence of the European Union’s regulations regarding orphan drugs.

“The original purpose of this legislation, passed in 1999, was to encourage drug companies to conduct research into rare diseases and develop novel treatments. However, as the rules are currently enacted, many drug companies merely address their efforts to licensing drugs that are already available rather than developing new treatments,” they wrote. “Once a company has obtained a license, the legislation then gives the company sole rights to supply the drug. This in turn allows the company to set an exorbitant price for this supply and effectively to bar previous suppliers of the unlicensed preparation from further production and distribution.”

When BioMarin began the U.S. trials needed for FDA approval, Jacobus Pharmaceuticals raced to conduct its own. With FDA approval would come seven years of exclusive rights to produce, license and sell the drug in the U.S.

In 2012, BioMarin sold the U.S. license for Firdapse — 3,4-DAPP — to Catalyst Pharmaceuticals, which completed the U.S. studies and applied for FDA approval. Catalyst’s leadership said they did so to help patients with LEMS.

“Our rationale for pursuing FDA approval for Firdapse was to ensure that all — all patients — could have access to an evidence-based treatment,” McEnany said on Dec. 13. He added that Firdapse has undergone safety trials and will be accessible to all patients, not just those in clinical trials.

But in an editorial published in the journal Muscle & Nerves in December 2015, more than 100 doctors expressed concerns that Catalyst could put shareholders’ profits over patients’ needs.

“What is particularly troublesome to us is a ‘loophole’ in the (Orphan Drug Act) that allows companies to receive FDA market exclusivity under the ODA for older, existing drugs, such as 3,4-DAP,” they wrote.

While some of the FDA-approved medications that receive orphan drug status were created with substantial investment in research and development that may justify a higher price, companies that seek approval for existing medications don’t incur those same costs, the authors said. In the case of 3,4-DAP, they pointed out, there had already been trials to ensure the drug’s safety, and it had been in use in the U.S. and Europe for decades.

“We look forward to FDA approval of 3,4-DAP, because this will facilitate convenient access to an effective, high-quality drug for all LEMS and (Congenital Myasthena Gravis) patients,” the doctors wrote. “However, we have become increasingly concerned that, if granted an exclusive U.S. marketing license for 3,4-DAP, the Catalyst price of Firdapse will be equal to or greater than its price in Europe.”

Supporters of the FDA approval of Firdapse argued that it filled a need and would help more patients.

Catalyst estimated in December that Jacobus’ compassionate use program and its own expanded access program and clinical trials were only supplying about 10 percent of the LEMS patients in the U.S. with medication.

The approval of Firdapse wasn’t a surprise, according to Dr. Donald Sanders, a professor of neurology at Duke University.

Dr. Sanders has been researching LEMS and related neuromuscular illnesses for more than three decades. He also worked with Jacobus to get the medication to patients through the FDA’s Expanded Access program.

“We have a large clinic of patients with LEMS here at Duke who have benefited greatly from the compassionate use program,” he said.

For Dr. Sanders and the LEMS patients at Duke, the news of the FDA’s approval may have been expected, but approval from insurance companies still takes time.

Patients must get a prescription from their doctor and submit it. Then, the pharmacy must send a request to the insurance company. Because Firdapse is a new medication, the insurance company must look into the medication and decide whether or not they’ll pay for it.

The process can move slowly, and some patients have struggled to get a bridge supply of Firdapse while they wade through insurance red tape.

“I’m hearing of many patients who are on their last day dose of 3,4-DAP and they have still not been able to get their Firdapse,” Dr. Sanders said.

In the meantime, Jacobus is legally barred from providing 3,4-DAP to patients. So are compounding pharmacies.

And without their medication, most patients will see their quality of life plummet. Deike says symptoms leave her unable to do much of anything — heavy legs, difficulty breathing, and intense fatigue caused by the effort of moving a body that doesn’t want to cooperate with her.

That’s typical for untreated LEMS patients, Dr. Sanders said.

Regaining her life

Marta Deike grew up in North Stockton and attended Tokay High School. As a teen, she ran for the cross country and track teams at her alma mater.

After graduating in 1981, she spent time in San Francisco and Minnesota, before moving to New York in 1996. She earned her law degree at St. John’s University, and worked as an assistant district attorney in Nassau County.

Deike was thriving in that role when, in December 2005, she began experiencing some odd symptoms.

“I noticed I couldn’t cross my legs, like my hip flexors were paralyzed,” she told the News-Sentinel in November 2014, while training to run in the Womble Rumble.

Soon, her shoulders weren’t moving as they should. Deike saw a neurologist, and was diagnosed with myasthenia gravis. She underwent surgery to remove her thymus gland, in the hopes that it would relieve her symptoms. It did not.

Deike steadily grew weaker, spending close to a year in bed, unable to move much.

Then, a second neurologist spotted an antibody in Deike’s blood that pointed to Lambert-Eaton Myasthenic Syndrome. He prescribed her with 3,4-DAP, and she got the drug from Jacobus.

When she took the first pill, the improvement was almost immediate.

“Within 20 minutes, I was able to stand up, and sit down, and stand up again,” she said in 2014. “It just felt like I could move.”

She undergoes the same process today, settling down in her kitchen, taking her first dose of the morning, and waiting for the medication to kick in. Within minutes, she goes from slow, with blurred vision and slurred words, to close to normal function.

“My reaction to this medication was so dramatic,” she said last week.

Deike is grateful to Jacobus for giving her a life.

Now, she’s trying to figure out how Catalyst is going to change that. It goes beyond price, she said. She knew getting 3,4-DAP for free was lucky, and she doesn’t mind paying what the drug is worth.

“I don’t want anything for free,” she said.

But the new price tag means Deike now has to work to convince her insurance company that she needs Firdapse.

She has to change her dose and get used to a new pill schedule.

She has to change her medical alert bracelet.

“It’s like Jacobus never existed,” she said.

Deike is active on a Facebook group for LEMS patients, and they’re all worried, she said. They’ve struggled to get information about the transition.

She worries that she won’t be able to continue living the life she’s carved out for herself. She worries she might end up in assisted living. She worries that the slight change in the formula might cause a bad reaction and leave her without any options.

“I need some assurance that everything is going to be OK,” she said.

Hopes and fears

Not every LEMS patient is upset by the news of Firdapse’s approval.

Dawn DeBois, a blogger for the Bangor Daily News in Maine, has multiple autoimmune diseases including LEMS. DeBois acknowledged that there are worries about insurance coverage and access to Firdapse, but she’s also excited about the potential the FDA approval has to raise awareness of LEMS.

“This means doctors will have heard of your rare illness that affects only 1 in 1 million people,” she wrote in November, after news of the FDA approval broke. “Up until now, many doctors have not even heard of it.”

It also means that, once they are diagnosed, LEMS patients won’t have to go through the paperwork and procedure required by the FDA’s Expanded Access program to get medication that treats the debilitating symptoms.

“... our invisible illness is now visible in the form of an FDA-approved drug to treat our illness and give us our quality of life back,” she said.

Catalyst has said it plans to explore whether Firdapse can be used to treat related rare diseases such as congenital myasthenic syndromes, MuSK antibody positive myasthenia gravis, and spinal muscular atrophy type 3.

The company said in December that it is also working on a longer-acting formula that would require fewer doses each day, and may last throughout the night.

Others are afraid.

Lodi’s Deike worries that with Firdapse, she will lose the quality of life she’s fought so hard to achieve.

That’s because even if her insurance and the financial assistance program at Catalyst allow her to continue receiving Firdapse, the maximum allowed dosage of the new medication is 80mg daily.

Deike takes 100mg of 3,4-DAP each day to have close to normal — but still slightly limited — function.

She’s most worried that she won’t be able to help coach the Tokay cross country team anymore.

“I love it so much,” she said.

Deike is proud of her work with the students at Tokay. The afternoon heat can make her LEMS symptoms harder to deal with. It makes her muscles relax, and for Deike and other LEMS patients, their muscles are too relaxed in the first place.

Still, she powers through it, because working with the team is rewarding. And after all, each of the kids have faced down their own challenges and overcome them.

“They’re really good kids,” she said.

Deike has a 3,4-DAP regimen that gets her through the day: she takes her first dose of 3,4-DAP at 7 a.m., then 11⁄2 pills every 21⁄2 hours until 10 p.m.

With Firdapse, she will be starting at 7 a.m. and taking her last dose at 5 p.m.

That won’t leave her with enough energy to do anything very strenuous, especially later in the day.

“I won’t be able to coach anymore,” she said.

Deike recalled a camping trip gone wrong last July. She ate something that disagreed with her, and couldn’t keep her pills down.

“The next morning, I couldn’t stand up,” she said.

Her partner Randy had to carry her out.

That’s the existence Deike fears if she’s unable to get access to her medication at the dose she needs.

“This drug literally saved the quality of my life,” she said.

Other patients have similar stories.

Kansas man Will Schuller, 22, first developed symptoms around Halloween of his senior year of high school. He went downhill quickly, losing feeling in his limbs. By Christmas he was in a wheelchair, too weak to walk, and had to be pulled out of school.

Jacobus Pharmaceuticals’ 3,4-DAP got him back on his feet, and he’s now in college.

Schuller sees some upsides to the FDA approval of Firdapse. When he was diagnosed with LEMS, he had to travel from his home in Johnson County, Kan. to the Mayo Clinic in Rochester, Minn., and stay there for a while to get into the Jacobus program.

“For me it was really hard,” he told the Kansas City Star. “There was only, like, one doctor at Mayo Clinic who could prescribe it, and you would have to get the diagnosis confirmed and see him in person.”

Not every family can afford to visit the Mayo Clinic or the handful of other doctors who worked with the Jacobus program, he noted. And now, even if he changes doctors, he’ll be able to get his prescription.

But the cost has him worried.

“I know in Europe people are paying quiet a bit for the medicine, and every doctor I’ve talked to says it costs maybe $3 to make a bottle of it,” Schuller said.

His mother, Ann Schuller, was more blunt.

“Obviously the small LEMS community is frightened that they are now not going to be able to afford a drug they have been receiving for free for years,” she said.

In the national spotlight

Sen. Bernie Sanders, I-Vermont, put Firdapse in the spotlight this week. On Monday, he sent a letter sent to Catalyst Pharmaceuticals demanding that it justify its decision to sell Firdapse for $375,000 per year.

The cost of producing the medication costs about $1,600 to $6,000 per year, he said in the letter.

“Catalyst’s decision to set the annual list price at $375,000 is not only a blatant fleecing of American taxpayers, but is also an immoral exploitation of patients who need this medication,” he said. “Simply put, it is corporate greed.”

Sen. Sanders noted that Catalyst knew that clinical trials in the U.S. and Europe had already established the drug’s effectiveness in treating LEMS when it acquired the North American license for Firdapse.

“Catalyst did not invent the active ingredient in this drug, called 3,4-diaminopyridine (3,4-DAP),” he pointed out. “In fact, 3,4-DAP has been used to treat LEMS and related conditions for more than thirty years.”

Sen. Sanders demanded Catalyst explain the financial and non-financial factors leading to their pricing decision, including how much they paid for the North American licensing rights to Firdapse, price comparisons with the cost in other countries, and information about their expanded access program.

He also questioned whether Catalyst was directing patients in need of financial assistance to NeedyMeds.org, a national nonprofit for those who cannot afford their health care costs.

Catalyst is offering its own financial assistance program, but few details about the program were available Thursday.

“I am profoundly concerned that Catalyst’s actions will cause patients to suffer or die,” Sen. Sanders said.

Catalyst shared the following statement with the News-Sentinel: “Catalyst’s top priority is improving patient care in the LEMS community and potentially elsewhere within the neuromuscular community. We will respond to Senator Sanders’ letter in a timely manner and provide information about Firdapse and the programs that we have in place to raise awareness of LEMS, facilitate accurate and timely diagnosis, and broaden affordable patient access to an FDA-approved treatment.”

Catalyst did not respond to the News-Sentinel’s requests for answers to specific questions as of press time.

Dr. Nicholson Price, an assistant professor at the University of Michigan who specializes in law surrounding innovation in the life sciences, said Catalyst would likely counter by saying it was responsible for spending the money to get the treatment formally approved.

“In an ideal state, we’re not giving patients drugs for which we don’t have rigorous evidence that it works,” he told the Miami Herald on Tuesday.

But he said he has noticed a change in approach from some drug industry executives who formerly shied away from this kind of sticker shock. In 2017, pharma investor Martin Shkreli came under fire for raising the price of Daraprim, which is used to treat rare cases of toxoplasmosis, 5,000 percent from about $13 to $750. Shkreli was later indicted on unrelated securities fraud charges.

Prices of insulin, used to treat diabetes, and EpiPens, an emergency treatment for life-threatening allergies, have also increased sharply in recent years.

“The idea of, ‘I have a moral duty to make the most money for my shareholders as the CEO of a publicly traded company — I think that is a strand of thinking of business ethics that is hugely problematic,” Price said.

Setting a high price for a medication is perfectly legal, Dr. Sanders pointed out.

“I think it’s just now getting attention,” he said.

Unfortunately, it may be a problem that can’t be solved without legislative intervention.

The issue is the U.S. Orphan Drug Act, passed in 1983. It was originally conceived as a way to encourage pharmaceutical companies to research rare diseases like Huntington’s disease, Tourette syndrome and muscular dystrophy. Receiving an Orphan Drug designation — as Catalyst did with Firdapse — provides certain government benefits such as reduced taxes and seven years of exclusivity.

But the act never put any price controls in place, and that’s led to some unintended consequences.

“The (pharmaceutical) industry has taken advantage of the incentives to charge excessive profits and to reap windfalls far in excess of their investments in the drug,” said former California Rep. Henry Waxman, the primary sponsor of the Orphan Drug Act.

There’s also nothing in the act to prevent companies from doing what Catalyst did: finding an unapproved drug that’s already in use rather than developing something new.

At this point, the only way to change that is for political leaders to step up and close those loopholes, Dr. Sanders said.

“Congress could do it,” he said. “The FDA can’t, by law, do it.”

Until someone steps up, there’s nothing to stop companies from charging exorbitant prices for medication, especially when that medication is the only option.

“Patients are caught now between a rock and a hard place, and they are desperate for a solution,” Dr. Sanders said.

‘Back to square one’

Deike took her first dose of Firdapse on Thursday morning — slightly less than usual for her morning dose, in case she had a bad reaction to the slight change of formula.

A few of her fellow patients on Facebook had shared having migraines or a racing heart with the change of medication, and Deike was hoping to avoid that.

“I had absolutely no side effects like that,” she said. “My problem is I feel like I’m so weak.”

She thought that going up to the normal amount — 15 mg — for her second dose of the day would help, but it didn’t.

She tried to go through a normal day, jogging in the morning and running a few errands. But it was difficult, she said. Her neck, eyes and shoulders felt weak.

“I can’t lift my legs very well. I’m back to this kind of a waddle,” she said. “It feels like I’m back to square one, almost.”

Deike is looking into potential alternatives. She plans to visit a functional medicine doctor to overhaul her diet. She already tries to eat meals that won’t encourage any inflammation, avoiding beans, sugar, nightshade family plants, and other foods linked to inflammation. She’s been trying to follow the Wahls Protocol Diet, which has been helpful for some multiple sclerosis patients.

But there may be more she can do, and the doctor could have some other suggestions that might help.

Deike also plans to visit her neurologist in a month for a checkup with the new medication, and she will probably appeal for approval to receive a full 100mg of Firdapse a day instead of 80mg — the same as her 3,4-DAP dose. But even with that, she’s not sure it will be as effective as the medication from Jacobus was, despite the cost.

“That’s really disappointing, and I’m not sure what to do,” Deike said. “There’s nothing I can do.”

Andy Marso of the Kansas City Star, Rob Wile of the Miami Herald and Ashley Portero of the South Florida Business Journal contributed to this report.

Recommended for you

comments powered by Disqus