A 34-patient, single-arm trial was enough to bag Swedish Orphan Biovitrum's (Sobi’s) ultra-rare disease drug Gamifant both an Ash late-breaker slot and US FDA approval. But, as is often the case these days, it looks like launching the drug will be the hard part.
The number of patients with primary haemophagocytic lymphohistiocytosis (pHLH), the disease for which Gamifant is indicated, is already vanishingly small. Added to this is the fact that the disorder often goes undiagnosed, as non-specific symptoms mean that it can be mistaken for a virus.
Education, education, education
Sobi executives, talking to Vantage at the Ash meeting, did not seem too concerned about the risk of Gamifant’s launch falling flat. Carol Ann Satler, the group’s North American head of medical affairs, said the company had already bolstered its sales force and field medical team, and would have to educate physicians about the disease.
“We hope that with different initiatives, from peer-to-peer meetings to just having a new medication out there, will increase awareness and increase the diagnosis rate,” she said.
Still, the Swedish group, which acquired rights to Gamifant, known generically as emapalumab, from Novimmune for $50m in June, will want to make a return on its investment.
The drug, which had flown under the radar until the Ash late-breakers were revealed, is forecast to bring in $33m by 2020 according to EvaluatePharma sellside consensus (Ash 2018 preview – smaller groups get their turn in the spotlight, November 21, 2018). Even this relatively small number looks like a long shot, however.
Gamifant takes aim at a little-known disease: pHLH is newly diagnosed in only 80-100 people in the US each year. And the drug is only approved for a subset of these – patients who are refractive to or cannot tolerate existing therapy, dexamethasone and etoposide – meaning that the actual addressable market is a lot smaller.
Ms Satler was unable to say just how small, saying that the above figure came from a claims database and could not be broken down further. Sobi hopes to expand Gamifant into first-line disease, but a trial here might take another year or two to enrol, she added.
But the problem is obvious: even at 100% take-up of first-line as well as refractory patients Gamifant would need to be priced at over $300,000 per patient per year to meet the 2020 forecast. Analysts at ABG Sundal Collier predict that Gamifant's price will come in much lower, at $170,000 per year in the US, and $100,000 per year in Europe and Japan, although did concede that they were on the "conservative side".
Orphan drug, orphan pricing?
Rami Levin, president of Sobi’s North America division, would not give any details about Gamifant’s cost, saying this would be revealed at or closer to launch, due in the first quarter of next year.
He said: “I can tell you the feedback so far from payers has been extremely positive. They understand the severity of the disease, the importance of this first ever approved drug in pHLH.”
When asked whether ongoing pricing pressure could spell the end of the good times for rare disease drugs, which have so far largely escaped unscathed, he replied: “I think there’s still an understanding that these are almost separate, simply because the impact on the budget is relatively small.”
Gamifant should at least benefit from the fact that nothing else is specifically approved for pHLH, Ms Satler added, although some agents, like Jak inhibitors, are used off label.
Sobi will hope that the data presented at Ash will be enough to cement Gamifant’s ownership of this space. The abstract already revealed a 65% overall response rate with the product.
The goal of therapy, according to Ms Satler, is to get patients to a stem cell transplant, the only thing considered curative for pHLH. Sobi hopes to move Gamifant into first-line disease: seven patients in the study were previously untreated, and showed a similar efficacy to those receiving Gamifant second line, Dr Franco Locatelli of Bambino Gesù Children’s Hospital in Rome said during a press conference today.
Sobi is unlikely to run a randomised, controlled trial for first-line disease, however – Dr Locatelli noted that it would be unfeasible to do so "in a reasonable period of time" given the rare nature of pHLH.
Gamifant, an anti-interferon-gamma antibody that aims to damp down the hyperinflammation seen in pHLH, could also have use in other inflammatory disorders, Sobi believes.
A phase II study is ongoing in macrophage activation syndrome, and the company is looking at other diseases alongside Novimmune, which will continue to lead development. If Sobi cannot get away with charging a huge price for Gamifant, perhaps new uses might give the group a better chance of hitting forecast numbers.