An FDA Approval Is A Boon For A Drug Maker, But Could Come At A Major Cost For Patients


 
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By Meghana Keshavan

Vickie Moored can walk again. Her words don’t slur, her vision isn’t blurred, and she no longer collapses every day.

The 65-year-old from Elkton, Va., says she has her life back, thanks to the stunning efficacy of a cheap, but unapproved, chemical called 3,4-DAP. It’s a medication she would not have but for the largesse of a tiny, family-run drug maker that has been giving it out, for free, for decades.

But Moored, along with others who share her rare neuromuscular disorder, are concerned that their fortunes could change. The cost of the treatment will likely skyrocket — from next to nothing to potentially more than $100,000 without insurance — now that the Food and Drug Administration has approved a medicine to treat their disease, Lambert-Eaton Myasthenic Syndrome.

“There has been a long-standing need for a treatment for this rare disorder,” the FDA said in a statement this week announcing the approval.

The reality is that physicians have been prescribing 3,4-DAP, a nearly identical treatment, off-label, since the 1980s. It was never formally approved by the FDA; instead, LEMS patients pay about $300 to $500 a month to get the drug from a compounding pharmacy. That, or they’ve been supplied with the drug — for no charge — from the New Jersey-based Jacobus Pharmaceutical Co.

With an FDA approval in hand, however, Florida-based Catalyst Pharmaceuticals now has the ability to charge what could be hundreds of thousands of dollars — for a medicine that costs almost nothing to make. What’s more: Catalyst could block older forms of the drugs from being given to patients, even though they didn’t invent the formulation in the first place.

Catalyst, which declined to respond to requests for comment for this article, will release specific pricing information in mid-December. It says that an approved drug will help more patients get access to therapy — and some members of the LEMS community agree. Others, however, are devastated.

Drug pricing is an increasingly contentious issue in the U.S. Take the case of Turing Pharmaceuticals, which hiked the price of AIDS drug daraprim 5,000 percent when led by former CEO Martin Shkreli. Or Valeant Pharmaceuticals, which routinely increased the prices of all its drugs.

The Trump administration has launched a handful of measures in an effort to curb price hikes. Some of those efforts have been led by the FDA, but the FDA is a regulatory agency tasked with ensuring the safety and efficacy of drugs, and has not historically taken price into consideration when deciding whether to approve new treatments.

“This is a very political environment, and this sort of decision will raise a lot of interest — and a lot of criticism — in the FDA,” said Dr. Donald Sanders, a professor of neurology at Duke University who has treated LEMS patients for many years. He’s also worked as a consultant for Jacobus. “I’ve found it very difficult to believe anyone would risk creating a public firestorm by allowing a very expensive drug to replace another that’s already available — safely and for free.”

Dr. Ted Burns, a professor of neurology at the University of Virginia, says Catalyst is “profiteering” off of vulnerable patients, and calls its business model for Firdapse, the brand name of the drug, “exploitative.” In 2015, he penned an editorial — signed by more than 100 neurology experts — expressing grave concern that an FDA approval for Firdapse would spike treatment costs for LEMS patients. It’s unclear how much of the cost insurers will cover.

“This feels like a win for Wall Street and a loss for the rest of us,” Burns said. “It’s unfair. The patients pay. We all pay. Deductibles, premiums, and taxes will go up because of this. None of this makes sense.”

“So many of us are feeling desperate and scared and outraged,” said Sharon Southern, a LEMS patient in Australia who has been getting her 3,4-DAP from Jacobus since 2004. “Catalyst is sweeping in to look like the heroes — when they’re actually the opposite.”

Patients say the unapproved version of the drug works perfectly well — and has been transformative.

“I wouldn’t be alive today if not for 3,4-DAP: It allows you to move and breathe,” said Southern, who recalled that before treatment she used to feel profound weakness and a slowing of her reflexes. “It’s absolutely life-changing. And lifesaving.”

LEMS is an autoimmune disease, in which the body’s own defenses turn against the region connecting a person’s nerves and muscles. This disturbs the nerves’ ability to send signals to muscle cells, leading to severe muscle weakness and pain, and difficulty with walking, breathing, and eyesight. About half the time, it’s linked to non-small cell lung cancer. There are an estimated 3,000 patients with LEMS in North America, and another 6,000 in the European Union.

In the 1970s, Scottish scientists discovered 3,4-DAP — also called amifampridine — and by the 1980s, Swedish scientists were demonstrating that it worked in LEMS patients. The Muscular Dystrophy Association later asked Jacobus to manufacture 3,4-DAP because doctors wanted to study its use in LEMS, but didn’t have a steady supply of the chemical.

Jacobus agreed, and ever since has provided the drug to more than 1,000 of patients with LEMS, asking them only to cover postage costs, said Laura Jacobus, who runs the company with her father, David.

In 2000, Parisian researchers developed a shelf-stable version of 3,4-DAP by adding a phosphate group onto the amifampridine compound. The older version required refrigeration, which could be inconvenient for patients.

Amifampridine phosphate was licensed to a biopharma company, and the drug switched hands from one to another — until it was acquired by Bay Area-based Biomarin in 2009. Amifampridine phosphate was approved by the European Medicines Agency that year, and was given a new name: Firdapse.

It was also given a new price tag: $60,000.

Although it’s rare for private pharma companies to display generosity like Jacobus has, “it’s dirt cheap to manufacture the drug,” Sanders said.

When he first started prescribing 3,4-DAP back in the 1990s, his team at Duke would buy it in bulk from a chemical company for about $100 per kilogram. That was enough to treat several patients for several months. The school’s pharmacy would put the drug into capsules, and then Sanders would distribute it to his patients with LEMS.

Moored is one of them: Every six months she drives four hours, from her home in Virginia to Duke University in North Carolina, to pick up a half year’s supply of her medication. She pays a small fee to cover shipping costs for the refrigerated drug. She takes four pills a day.

To get 3,4-DAP, patients like Moored must work with their doctor to appeal to the FDA’s compassionate use program, which allows access to unapproved therapies if no other options are available. It’s not easy, and patients and physicians have had to wade through lengths of red tape to get 3,4-DAP. Still, the net result is a free and effective drug to treat LEMS.

Other patients that don’t have ready access to the Jacobus product can get the drug from about a half-dozen compounding pharmacies around the country, Sanders said. They’ll charge about $300 to $500 per month.

Firdapse will be much more costly.

In a 2015 presentation to investors, Catalyst Pharma estimated that it could make $300 million to $900 million on Firdapse sales, suggesting a price tag of perhaps $100,000 per person based on the estimated patient population. Other analysts have estimated the cost could run up to $300,000 per year.

There’s a divide among some in the LEMS community. Some patients and their families say they are grateful for Firdapse — and believe the FDA approval will guarantee access for all patients.

Leigh Shell, whose 24-year-old daughter, Sarah, has a congenital form of LEMS, is thrilled.

Sarah began showing symptoms of LEMS when she was just 15 — losing weight, having difficulty swallowing, passing out frequently. By the time she was a freshman in college, Sarah had to use a wheelchair. Her family had taken her to specialists in Atlanta, New Orleans, and Birmingham, Ala., for a diagnosis, and she’d been told she could have anything from a brain tumor to a rare, fatal genetic disease. When a doctor finally came upon the correct diagnosis, he retired.

“We were left without a doctor who knew what LEMS was, and how to treat it,” Shell said. “So there was no medicine available for her.”

Shell managed to get the drug from a compounding pharmacy, but was never instructed that the drug required refrigeration. So it quickly denatured, and never worked for her. Shell also tried to get the drug from Jacobus, but came up short.

“Nobody responded to us, because we didn’t have a doctor that was connected with Jacobus to get it for free,” Shell said.

(Jacobus says it currently provides 3,4-DAP for about 350 LEMS patients.)

The family eventually enrolled in a clinical trial Catalyst was running.

Sarah’s symptoms improved almost instantaneously after her first dose of Firdapse. After being in a wheelchair for a year, she was able to stand up and walk again. When Sarah was at her worst, she would rarely leave her home. Now, she’s 24, married, and works as a special needs tutor in Oceanside, Calif.

Along with other patients who have LEMS, the Shell family has received travel vouchers from Catalyst to attend conferences for patients with this rare disease. Sarah, and her mother, have also spoken at Catalyst, sharing their experiences as patient and caregiver.

They are grateful that Catalyst offered her the drug when they felt they had no options. Shell isn’t concerned about the cost: She called her insurer, Blue Cross Blue Shield, and they assured her they would pay for the drug.

“Our insurance company said they view this as a specialty drug — saying that because so few people need it, they’ll cover it,” Shell said. “They told us our out-of-pocket cost would only be $60 per month.”

Catalyst has said it plans to set up programs to help patients navigate insurance questions and apply for financial assistance once the drug is launched in the first quarter of 2019.

Burns, the University of Virginia neurologist, says Catalyst is taking advantage of a loophole in the Orphan Drug Act, which gives incentives to companies that develop drugs for rare diseases. Most of the time, biotechs use these provisions to invent new medicines — spending tens, even hundreds, of millions of dollars on research and development.

Catalyst did not invent Firdapse. But it did pay the necessary millions needed to test it in clinical trials, and apply for FDA approval.

“The big problem is, this is not what the Orphan Drug Act was designed to do,” Burns said. “It was designed to incentivize innovation. That’s not what’s happening here, because there’s no biopharmaceutical innovation.”

All the same, Catalyst could use its newly gained intellectual property to prevent patients from otherwise accessing 3,4-DAP, if it chose to do so. Compounding pharmacies can’t touch drugs that are protected under patent.

Catalyst disclosed in its 2017 annual report that it’s leaning heavily on the notion that insurers will pay for the drug: The company said that if payors don’t view Firdapse as cost-effective, and refuse to reimburse them for the drug, they may have to cost-cut — to the detriment of shareholders. And there’s no guarantee that insurance will pay for Firdapse.

There’s some precedent suggesting that could happen. In the U.K., the National Health Service will not reimburse for the Biomarin drug, leaving British patients to either pay for it out-of-pocket — or find an alternative source for 3,4 DAP. Citing this example, Moored is leery that Medicare would cover a costly drug like Firdapse.

“There is no reason in principle why the NHS should be required to prescribe a more expensive licensed drug when a pharmacologically identical drug is unlicensed for the treatment in question,” the NHS said back in 2010.

In other European countries, including Germany and Italy, regulatory bodies turned a blind eye to the LEMS situation, Sanders said — allowing patients to keep using whatever source for 3,4-DAP they’d been using all along. That was preferable to spending a large chunk of their national health budgets unnecessarily on this rare disease, Sanders said.

“Most European countries have figured out how to get it through some back door,” Sanders said.

In 2012, Biomarin licensed out Firdapse to Catalyst, investing $5 million in the Florida pharmaceutical company and handing over U.S. distribution rights. Catalyst plans to expand the drug’s use in other neuromuscular disorders, and is currently doing the clinical trial and regulatory legwork to get there.

In response to Catalyst’s plan to get Firdapse approved in the U.S., Jacobus decided to conduct a clinical trial of its own. Both companies published a spate of clinical data in recent years, and submitted applications for FDA approval.

Laura Jacobus said her family’s version of 3,4-DAP is still up for FDA review, but would not say when. But, in any case, Catalyst got its submission in first.

“It took too long for us to have enough of a war chest,” Jacobus said. The small company sells drugs to treat diseases like tuberculosis and leprosy, but lacks the financial backing — and the stockholders — to quickly raise money.

“From a commercial point of view, we didn’t do it right,” she added. “We thought we were doing the right thing by always making our drugs affordable — making this drug available in a compassionate use basis — and we got stung.”

Jacobus accepts the FDA’s judgment on Firdapse, and believes that their data must have demonstrated that it was safe and effective. It’s still unclear whether Jacobus will keep producing 3,4-DAP — moving forward, it all depends on FDA regulations around compassionate use. If it’s just for a handful of patients who live abroad, the company will most likely not be able to keep producing the drug, she said.

Jacobus said she’s happy that she’s been able to build up relationships with LEMS patients over the past 25 years, and help them live better lives. She says she will continue to wish them all the best.

 
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