Corbus Pharmaceuticals will receive up to $25 million from the Cystic Fibrosis Foundation to help finance a six-month Phase 2b clinical trial of lenabasum (formerly known as anabasum) to treat cystic fibrosis patients.
“To the best of our knowledge, this is the second-largest award they’ve ever given,” Yuval Cohen, Corbus’ CEO, told Cystic Fibrosis News Today in a phone interview from New York. “We’re absolutely delighted. This is a much larger award than normal, and it enables us to carry out the study.”
The double-blinded, randomized, and placebo-controlled trial will enroll 415 people with CF ages 12 years and older and at increased risk of pulmonary exacerbations — severe events associated with acute worsening of respiratory signs and sometimes irreversible decline in lung function.
Lenabasum is specifically designed to trigger the resolution of inflammation without suppressing the body’s natural immune response — a problem that has bedeviled other anti-inflammatory agents.
The oral therapy was given orphan drug designation and fast track status by the U.S. Food and Drug Administration (FDA) in 2015, and orphan drug status by the European Medicines Agency in 2016 — the regulatory body of the 28-member European Union.
Data from a Phase 2 study (NCT02465450), released in March 2017, showed that twice-daily treatment with lenabasum (20 mg twice a day) caused a 75 percent drop in the annualized rate of pulmonary exacerbations. That trial, which included 85 patients at multiple sites in the U.S. and six European countries, lasted 84 days with a 28-day follow-up period, and was supported by a $5 million award from CFF.
“People with CF and their physicians understand the need to reduce pulmonary exacerbations, a major driver or disease burden,” James Chmiel, the study’s co-principal investigator, said in a Jan. 30 press release. “New treatments are essential, given that most adolescent and adult patients have at least one episode per year.”
The upcoming CF trial is the first approved by the FDA to have as its sole primary endpoint the event rate of pulmonary exacerbation rather than forced expiratory volume in 1 second (FEV1; a standard measure of lung function).
“For the past 25 years, every CF drug that was novel — primarily, but not only, the Vertex drugs — have been approved based on the same primary outcome, FEV1,” said Cohen. “This has been a box no one has managed to get out of.”
Barbara White, chief medical officer at Corbus, underscores the importance of potential treatments like lenabasum, which aim to reduce the number of such exacerbations.
“Multiple measures could be used, but in our case, lenabasum resolves inflammations. And with that underlying mechanism, it is appropriate to look for clinical benefits in an inflammatory event,” she said in the interview. “A pulmonary exacerbation is very serious and associated with bad outcomes in CF patients, so it is an excellent reflection of an event of importance.”
White added, “About half the lung function loss of CF patients occurs as a result of these exacerbations.”
Besides the expense of an exacerbation — each can cost anywhere from $30,000 to $120,000 in the U.S., depending on where a patient is hospitalized — such events make patients sicker in the long run.
“A patient will end up in the hospital, they’ll have to receive antibiotics intravenously, and will probably be in intensive care or in an isolation ward,” Cohen said. “They’ll have staff around them 24 hours a day, and that can last from two to six weeks. When they come out of the hospital, they’re not the same person; their lungs are weakened. It’s during an exacerbation that a CF patient will pass away.
“We don’t know why it happens,” he said. “But we do know that when it happens, it’s because their immune systems become especially destructive.”
Measuring changes in pulmonary exacerbation rates rather than FEV1 as a primary efficacy endpoint is crucial, Cohen said, because “it permits us to conduct a very meaningful study that will give us clear answers in a shorter amount of time with fewer patients … If we were going after FEV1, we’d probably need to do 1,500 patients for about a year.”
Expected to open in the coming months, the study will enroll patients at about 100 sites in the U.S., Canada, Europe and Australia, as well as in Cohen’s native Israel.
“This clinical program was designed by working very closely with the CFF, as well as the European Cystic Fibrosis Society and a group of international CF specialists,” Cohen said.
He emphasized the trial will include participants regardless of their underlying CFTR mutation, infection or background medications.
“We accept all CF mutations. It doesn’t matter what mutation they have, they can be part of the study,” he said. “It doesn’t matter what infection or pathogen they have. They can also be in the study as long as they’re on any standard background medication. So if they’re already on Orkambi or Kalydeco, they can stay on those drugs during the study. That’s very new.”
The fact that lenabasum is a pill rather than a nebulizer is also a plus, he said, since CF patients can find nebulizers inconvenient.
“We know about the safety of this drug to date,” Cohen said. “So far, it has been very well-tolerated. Side effects were mild and rare. We’re very pleased with that, since some CF drugs have difficult side effects.”
Lenabasum is in four clinical programs. Besides CF, the therapy is being tested as a potential treatment for systemic sclerosis, dermatomyositis and lupus. “All four of these trials involve very rare, serious life-threatening diseases that have chronic, destructive inflammation at their heart,” he said.
Corbus — headquartered in Norwood, Massachusetts — has raised $120 million from investors since its founding three and a half years ago, Cohen said, plus some $45 million in awards and grants, including this most recent CFF award.