By ED SILVERMAN @Pharmalot NOVEMBER 15, 2019

Last February, Barbara Moore switched to a new medicine to combat a rare neuromuscular disease that had plagued her for nearly a quarter of a century.

She had not planned to do so, but Moore had no choice: An effective treatment she had been taking all those years was forced off the market. In late 2018, Catalyst Pharmaceuticals (CPRX) was granted exclusive marketing rights to sell its new drug, called Firdapse, after the Food and Drug Administration approved the medicine. The move precludes any competition for seven years.

But within two weeks, she began suffering a debilitating setback.

“I had been a living a normal life on the old drug. But the new one was a nightmare for me. My legs got weaker. It got so bad that I couldn’t get in and out of a car. The drug sent my whole body into a tailspin,” said Moore, 68, a former city employee in West Sacramento, Calif.

Moore is not alone. Over the past few months, about 30 people who suffer from Lambert-Eaton myasthenic syndrome, or LEMS, have switched back to the older treatment, known as Ruzurgi. For more than two decades, a small, family-run company called Jacobus Pharmaceuticals made its drug available on a compassionate use basis to a few hundred people while pursuing formal FDA approval.

Last May, however, the FDA took an unexpected and controversial move. Following an outcry over the $375,000 annual price tag for the Catalyst drug, the agency approved Ruzurgi for anyone 17 years or younger. In regulatory parlance, this means doctors have to prescribe the drug off-label for adults, which is another way of saying it would be prescribed for an unapproved use.

Of course, switching from one drug to another due to side effects or ineffectiveness is hardly an unusual development in the world of medicine. It happens every day. And so does off-label prescribing. But the switching occurs against an ongoing residue of resentment over the cost for Firdapse, even though Catalyst arranged for patient assistance programs that bring the monthly cost down to $10 or less.

For these reasons, Catalyst executives told analysts earlier this week, they expected discontinuation rates of 20% to 25% after the Jacobus drug reappeared this summer. Pricing may play a role, though. Jacobus charges $80 a tablet, which is pricey, but less than half of the $171.23 Catalyst charges, a gap that can be attractive to insurers. Yet Catalyst told analysts this week that only a “trickle” of patients returned to the Jacobus medicine.

“We’ve seen what I call a minor exodus,” Catalyst chief executive Pat McEnany told us. “We think any patients who favored Ruzurgi over Firdapse have probably already made the switch. And we’ve found a number of doctors that just will not prescribe off-label.” He noted that 500 LEMS patients — including 170 who were previously untreated — are now taking Firdapse, which represents about one-third of the 1,500 people that Catalyst estimates have LEMS in the U.S. (This does not include another 1,500 people whom the company believes are misdiagnosed or undiagnosed).

Even so, patient preferences are being watched closely, especially by Wall Street, in the aftermath of the uproar triggered by the two FDA approvals. And on a wider scale, the episode has highlighted the vagaries of orphan drug exclusivity, the ongoing national debate over pricing for new medicines, and the extent to which the FDA might address disparities in the marketplace.

“This whole situation has been disappointing,” said Dr. Eric Sorenson, who heads the division for neuromuscular medicines at the Mayo Clinic, where he treats about half of the 60 LEMS patients seen at his facility. “On the whole, the LEMS community is not real happy with Catalyst. The company did not do a lot to generate good will. And at the end of the day, the prices mean higher insurance costs are passed on to everybody else.”

Here is the backstory: For more than two decades, an estimated 300 to 400 LEMS patients received the Jacobus drug at no cost, thanks to its compassionate use program. But because the drug was not approved by the FDA, Catalyst saw an opening. Several years ago, Catalyst licensed Firdapse from a company called BioMarin Pharmaceutical (BMRN) and began what became a yearslong horse race to win FDA approval.

The move prompted trepidation among dozens of physicians, who wrote an editorial in a medical journal in 2015 expressing concern that a drug distributed for free for so many years might soon cost patients a lot of money. How so? Catalyst was testing essentially a slight variation of the same medicine sold by Jacobus. And whichever company was first to win FDA approval would also gain orphan status.

This designation refers to medicines used to treat small patient populations, but also comes with seven years of market exclusivity. In November 2018, Catalyst won the race, but was quickly denounced due to the $375,000 price tag for Firdapse. The move sparked outrage. Sen. Bernie Sanders (I-Vt.), in particular, railed against Catalyst for “immoral exploitation” and asked the FDA to approve the Jacobus drug as well.

For the most part, though, the bad publicity soon evaporated, largely because Catalyst established patient assistance programs which in some cases eliminated out-of-pocket costs. Still, the Firdapse approval generated debate over the wisdom of conferring orphan drug status because Catalyst did not invent or develop the drug.

The FDA then stepped into the fray by approving Ruzurgi. The regulator never addressed the pricing issue, but in effect created an end-run around the Catalyst drug because the Jacobus drug could be prescribed off-label. And while Jacobus did not sell Ruzurgi at a bargain rate, its pricing has given doctors ammunition when talking to recalcitrant insurers about approving off-label prescriptions.

Catalyst quickly responded. In June, the company filed a lawsuit accusing the FDA of acting “arbitrarily and capriciously” by applying different standards when it approved the Jacobus medicine. Moreover, the company alleged the agency unfairly trampled on its right to seven years of exclusive marketing, hindering its ability to recoup its purported $100 million investment.

For now, the court case is plodding along, leaving Catalyst to pursue victory in physician offices and clinics. Toward that end, the company disclosed plans this week to double its sales force and add several other employees to interact with doctors. The move reflects the need to ensure that doctors are persuaded to stick with Firdapse not only for existing patients, but also for others who are later diagnosed.

To what extent the company can succeed remains to be seen.

Catalyst stock has been bouncing up and down, but some Wall Street analysts are giving the company the benefit of the doubt. Recent sales and projected near-term sales “do indicate new patient starts have largely reached a steady state following the initial” product launch, Piper Jaffray analyst Joseph Catanzaro wrote in an investor note.

One Firdapse patient reported the drug has proved beneficial, even slightly better than the Jacobus drug. Kristina Patafio, 52, a Staten Island, N.Y., real estate agent who was diagnosed with LEMS in early 2018 and initially took Ruzurgi, told us she is “doing a lot better now,” and hasn’t made a copayment.

Meanwhile, physicians seem uncertain why some patients may respond better to one drug or the other. There were 140 adverse events associated with Firdapse reported to the FDA through the end of September, but without a head-to-head study, there is no evidence to draw conclusions. “It’s just very hard to say,” said Dr. Khosro Farhad, a Massachusetts General Hospital neurologist who treats a handful of LEMS patients, one of whom switched back to Ruzurgi.

For the moment, some physicians speculate the clamoring among some patients for the Jacobus drug may reflect a comfortable familiarity with the medicine. But Sharon Southern, who administers a Facebook (FB) page for LEMS patients, said she continues to field complaints that Firdapse has proven inadequate. “It’s a consistent story,” she told us.

Going forward, the decision making may reflect the marketing efforts.

“There will be, over time, newly diagnosed patients who haven’t received treatment previously and won’t have that perspective to know what the other drug would have done,” said Mayo’s Sorenson.

“But in most instances, I think most specialists will favor Jacobus simply because of the relationship they have had with the company over the years. They provided the drug free of cost. And most of us have had a much better relationship with Jacobus. Out of the gate, it was contentious with Catalyst,” he continued, noting there are about 50 physicians actively treating LEMS in the U.S.

“My guess is more patients will go on Ruzurgi as along as insurers allow it, especially since the price will provide incentive. And so the practice will shift toward Ruzurgi as time goes on.”

About the Author

Ed covers the pharmaceutical [email protected]@Pharmalot