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Free Myasthenic Syndrome Drug Program Threatened in Race for FDA Approval

By Kurt Samson

For two decades a small, family-owned pharmaceutical manufacturer in New Jersey, has provided patients with Lambert-Eaton Myasthenic syndrome (LEMS), a rare autoimmune disorder causing severe muscle weakness and often associated with cancer, with the only drug known to be effective — for free.

      Although the safety and efficacy of the drug is well-established, it has never been formally approved by US Food and Drug Administration (FDA) through the standard clinical trial/new drug process. Instead, the agency has allowed Jacobus Pharmaceutical Company, in Princeton, NJ, to provide the drug under the “compassionate use” exception to normal approval channels, granted for certain orphan drugs where no commercial product is available. 

      But now Florida-based Catalyst Pharmaceutical Partners, Inc., is pressing forward with a newer version of the drug, through an agreement with a European manufacturer, and is recruiting patients into a phase 3 study that, if successful and granted FDA approval, would severely limit, if not end, the free drug program. Catalyst raised more than $50 million to purchase US licensing rights from the multinational BioMarin Pharmaceutical, Inc., based in Novato, CA, and to underwrite clinical trials in the US. BioMarin gained European approval for the new drug in 2010.

     At issue is the drug 3,4-diaminopyridine (3,4-DAP), which can significantly improve muscular symptoms in many LEMS patients, often allowing immobilized wheelchair-bound individuals to walk again. 

     The new version being tested by Catalyst, amifampridine (Firdapse™), contains the phosphate salt of 3,4-DAP. In Europe, where patients had been able to purchase 3,4- DAP from compounding companies for under $2,000 per year, the price jumped to more than $60,000 after amifampridine was approved. The cost was so high that health agency officials in the United Kingdom eventually refused to cover the drug.

     But Catalyst said that its version is more stable than 3,4-DAP, which must be kept refrigerated, and can be stored at room temperature for at least three years. 

     The controversy was below the radar until an Oct. 18 article by Adam Feuerstein on the investment blog The Street criticized Catalyst for trying to capitalize on orphan drug patients. If Catalyst is able to get its product approved through a successful phase 3 clinical trial, Jacobus will have to halt its free drug program.

Catalyst Chief Executive Officer Patrick J. McEnany told Neurology Today in a telephone interview that the fallout from the negative article has hurt the company, saying that the company’s stock has fallen by 50 percent. Catalyst has also been made aware of several class action lawsuits that have been filed against the company as well as one or more of its officers and directors, alleging violations of federal securities laws. 

     “It is a little discouraging,” he said, but emphasized that the company “believes the suits lack merit and will be vigorously defended” by Catalyst. He also said the company had conducted market research which reviewed pricing and coverage with several major US insurers as well as Medicare officials.

Laura Jacobus, who together with Claire and David Jacobus, is co-owner of Jacobus Pharmaceutical Company, told Neurology Today in a telephone interview that over the years, the family has helped an estimated 600 patients, the majority with LEMS, through the company’s compassionate distribution program.

     She said that she believes that some Catalyst investors were surprised to learn that the drug has been used for 20 years in the US, or that the Jacobus free program even existed. But what makes the whole issue even more surprising, she said, is that it was Jacobus research data that BioMarin, the company that licensed the drug to Catalyst, used in its efforts to gain European approval in the first place.

      “We only want to do the right thing. We have never advertised or marketed 3,4-DAP, and we do not believe there is any need for copycat drugs that need splash to gain attention. We just want to continue doing what we have been doing for years by making 3,4-DAP available for individuals in need.”

     But Catalyst’s McEnany said introducing an FDA-approved product will raise awareness of LEMS among physicians, thereby increasing the diagnosis of the disorder in patients with symptoms who might otherwise be mistakenly treated for similar conditions. This too should help better determine the
actual prevalence of LEMS in the general population, he added.

      “Right now Jacobus is providing 3,4-DAP to only around 200 patients, but there are many more who are not receiving treatment.” Many sources point to a prevalence of 3,000 to 4,000 cases in Europe or 1 case per 100,000 individuals in the U.S. However, historically, once a drug for a rare condition is approved, more patients learn about it and come forward.

     Yet, Kathy Ales, MD, medical director at Jacobus, told Neurology Today that if Catalyst is awarded FDA approval, many patients will no longer be able to afford treatment, and almost all of them will face insurance reimbursement issues, regardless of whether they are covered by commercial carriers or through Medicare. 

     However, if all goes well and Jacobus is granted approval, the company will retain its ability to provide the drug through the standard FDA approval process and make it available at a reasonable cost, through wholesale and retail drug outlets. If patients cannot afford to pay, the company’s existing compassionate use program will still be preserved, Laura Jacobus noted.

Catalyst has initiated a large randomized, double-blind, placebo-controlled phase 3 trial followed by an open-label extension period in some 36-patients across 19 sites in the US and Europe. Catalyst also expects to add approximately six sites in the US, Canada, South America, and Europe in the near future. The company said Oct. 31 that it will report results from the double-blind trial in the second quarter of 2014. If the results are successful, it said it expects to submit a new drug application (NDA) with the FDA in the first half of 2015.

     Jacobus is in the middle of a phase 2 clinical trial, which was originally launched this year in January with a target of 30 patients; it is now seeking to expand the trial to other participants. It is actively recruiting LEMS patients, but lacking the resources of the larger company, it is asking neurologists to let their LEMS patients, especially those who have benefited from its 3,4-DAP program, know that they can volunteer as subjects for their trial. Jacobus hopes to complete its study by April 2014.

At Duke University Medical Center, in Durham, NC, more than 100 LEMS patients have received 3,4-DAP through the Jacobus compassionate use program over the years, including around 30 who are currently active recipients, said Janice M. Massey, MD, professor of neurology and chief of the Neuromuscular Division. 

     She was one of the authors of a clinical trial that validated the safety and efficacy of the drug, results of which were published in Neurology in 2000.

Dr. Massey told Neurology Today in a telephone interview that Catalyst will not comment on what they expect to charge for their product should it be approved, but she pointed to BioMarin’s pricing in Europe as an example of what to expect if it is approved in the US.

     “Before Biomarin introduced [amifampridine], patients in Europe obtained 3,4-DAP through drug compounding companies and paid the equivalent of $1,600 per year,” she noted. “Catalyst is a publically owned company, and its obligation is to its shareholders, not patients. If the company is granted approval, it will have an exclusive license to market this drug for the length of its patent, which is seven years after approval.”

      She too applauded the efforts of LEMS patients who now get 3,4-DAP through the Jacobus program for mobilizing online and in social media to raise awareness and inform patients about the company’s need for participants in its clinical trial.

“The spirit of volunteerism is really high among these patients, and they are very active in reaching out to others with the disease. As I understand it, enrollment is progressing well.”

• Sanders, D; Massey, J; Sanders, L; Edwards, L. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000;54:603-607
• Jacobus-sponsored LEMS trial:
The Street blog on Catalyst-Jacobus conflict:
• NINDS Information page on LEMS: 

      See this article in print, along with other groundbreaking neurology news, in the Dec. 5 issue of Neurology Today.