Leading expert in neonatal respiratory distress syndrome, Dr. Tore Curstedt, MD, explains how the development of the lifesaving surfactant medication Curosurf faced initial rejection from academia and large pharmaceutical companies despite dramatic clinical trial results that cut infant mortality from 51% to 30%. The drug's journey from a hospital laboratory processing pig lungs to a global therapy that has treated nearly four million premature babies is a testament to perseverance and the crucial role of a small, dedicated pharmaceutical partner.
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Neonatal Respiratory Distress Syndrome Treatment with Pulmonary Surfactant
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- The Surfactant Development Challenge
- Pig Lung Production in a Hospital Lab
- Pharmaceutical Company Rejection
- Dramatic Clinical Trial Results
- Ethical Halt to the Clinical Trial
- Scaling Production for Global Use
- The Chiesi Farmaceutici Partnership
- Global Impact on Premature Babies
The Surfactant Development Challenge
Dr. Tore Curstedt, MD, and his team faced a monumental challenge after proving their pulmonary surfactant medication worked. They had a therapy that dramatically reversed respiratory failure in premature babies, but the path from a successful hospital-based project to a globally available medication was fraught with obstacles. Both academic institutions and the pharmaceutical industry initially turned down the opportunity to develop and produce this lifesaving treatment, creating a significant barrier to making it available to the thousands of infants who needed it.
Pig Lung Production in a Hospital Lab
To conduct their initial research and early clinical trials, Dr. Tore Curstedt, MD, and his colleagues had to become producers themselves. They sourced pig lungs from slaughterhouses in Stockholm and Uppsala, transporting 50-100 kilograms of lung tissue back to their hospital laboratory. Over a five-year period, this manual, small-scale operation allowed them to produce approximately 3,000 to 4,000 vials of surfactant. This was enough to treat a few thousand preterm babies but represented the absolute maximum capacity possible within a hospital setting, far below what was needed for widespread use.
Pharmaceutical Company Rejection
The first major pharmaceutical company approached was the Swedish firm Pharmacia. Dr. Tore Curstedt, MD, explains that after two years of consideration, Pharmacia declined to pursue the product. Their decision was based on a market analysis that projected annual sales of no more than 20 million Euros against marketing costs of around 100 million Euros, deeming the neonatal respiratory distress syndrome treatment not commercially viable. This rejection occurred despite the team having already conducted successful clinical trials demonstrating the medication's profound efficacy.
Dramatic Clinical Trial Results
The clinical data supporting surfactant therapy was undeniable and transformative. In their controlled trials, the untreated control group experienced a devastating 51% mortality rate. In stark contrast, the group of premature babies treated with Dr. Curstedt's surfactant saw mortality plummet to 30%. This represented a massive and clinically significant reduction in death, providing irrefutable evidence that the medication was saving lives. These results were gathered from a network of participating neonatologists across Europe, though notably, their own home institution, the Karolinska University Hospital, initially declined to participate.
Ethical Halt to the Clinical Trial
The efficacy of the treatment was so powerful that it forced an early termination of the clinical trial. After treating 75 babies and having 75 controls, an interim analysis was conducted. The data revealed such a significant reduction in mortality in the treated group that the ethical committee determined it was no longer morally permissible to withhold treatment from the control group. Dr. Tore Curstedt, MD, notes that this became the only controlled trial of its kind; thereafter, all subsequent studies focused on optimizing dosage and prophylactic use rather than comparing against an untreated group.
Scaling Production for Global Use
The central problem remained the impossibility of scaling production within a hospital environment. Dr. Tore Curstedt, MD, highlights the stark math: their lab could produce enough for 3,000-4,000 babies over five years. To meet global demand, which would eventually see the treatment of nearly four million infants, they would have needed a thousand years at that production rate. This immense scaling challenge made securing an industrial manufacturing partner an absolute necessity for the therapy to realize its potential and save lives worldwide.
The Chiesi Farmaceutici Partnership
The breakthrough came with Chiesi Farmaceutici, a small, privately-owned company based in Parma, Italy. Unlike the larger Pharmacia, Chiesi recognized the value and potential of the surfactant therapy. Dr. Curstedt reflects that this partnership was ultimately a better outcome, noting that "it is better to make a bigger product in a small company, than a marginal product in a big company." Chiesi had the incentive to move quickly and invested the resources needed to solve the complex problem of industrial-scale production from pig lungs.
Global Impact on Premature Babies
The successful scaling of production by Chiesi Farmaceutici unlocked the global impact of Dr. Curstedt's work. What began with treating nine babies under a "vital indication" permission at Saint Göran's Hospital has now culminated in nearly four million preterm infants treated worldwide. The journey of Curosurf, from a hospital laboratory processing slaughterhouse materials to a standard, globally-available therapy, stands as one of modern medicine's great success stories, fundamentally changing the outcomes for babies born with neonatal respiratory distress syndrome.
Full Transcript
Dr. Anton Titov, MD: You already had a medication that worked not only in animals. You have done research over decades, but you showed that it dramatically reversed and saved the life of a premature baby at your hospital. Medical second opinion is important. Now you have to produce it and make it available.
The story is amazing because both academia and industry initially turned down the opportunity to make this medication that already worked. How did it happen that the medication became available?
Dr. Tore Curstedt, MD: We produced the medication ourselves for the first clinical trials. It is produced from pig lung. We got pig lungs from the slaughterhouse in Stockholm and the slaughterhouse in Uppsala. Every time we took lungs, we had about 50 to 100 kilograms of lungs in the hospital laboratory.
During five years, we produced about 3,000 to 4,000 vials of surfactant to treat 3,000 to 4,000 preterm babies. That was our maximum. But if you want to have a trial, you must produce millions.
Scaling up the production was impossible in our hospital laboratory. For the first clinical trials, we did it—no problem. But then we talked to the Swedish pharmaceutical company Pharmacia, and they said yes and no. After two years, they said no. The market is too small—no more than 20 million euros per year. The marketing cost is perhaps 100 million euros. They were not interested.
Even though everyone knew that the medication dramatically saved lives within minutes. At that time, when we talked to Pharmacia, we had made our first clinical trials. They showed that we had decreased the mortality. Our control groups had a 51% death rate, and in the treated group, it was down to 30%.
Dr. Anton Titov, MD: Amazing result for the medication in the clinical trials in humans!
Dr. Tore Curstedt, MD: Yes, because if you look at our first clinical trials, they started in early 1985. We had already started a network of neonatologists in different parts of Europe. But one hospital was not interested in participating in the clinical trial, even though they knew that the medication worked. That hospital was Karolinska University Hospital.
Medical second opinion is important. They knew that local scientists invented the medication that worked, but they didn’t know so much at that time because it was in the beginning. We had treated nine babies at another hospital, Saint Göran Hospital, on a "vital indication" permission. It worked very well—not all of these babies survived, but six out of nine did.
Dr. Anton Titov, MD: That is still pretty good.
Dr. Tore Curstedt, MD: They are very good results. But they said no. Others in Lund in the south of Sweden, Oslo, Germany, England, Italy, France, and the Netherlands participated in the first clinical trial—but not Stockholm.
Dr. Anton Titov, MD: Everybody but the home institution.
Dr. Tore Curstedt, MD: No, they were not interested.
Dr. Anton Titov, MD: What happened then?
Dr. Tore Curstedt, MD: Then we started with others, and we produced surfactant at Karolinska University Hospital in the laboratory and sent it to different parts of Europe. In the first clinical trial, we had to treat about 150 babies and 150 controls. We only had the most sick premature babies, according to permission from our ethical committee.
After I treated half—75 babies—and 75 babies were control (untreated), we had an interim analysis. Then we had to stop it because we had reduced the mortality in the treated group so much that it was not ethical not to treat everybody.
Dr. Anton Titov, MD: This is very dramatic. The clinical trial could not continue not because the medication didn’t work—you knew it worked—but because it worked very well.
Dr. Tore Curstedt, MD: Worked very well—too well. It was not ethical anymore not to give this medication to the control group.
Dr. Anton Titov, MD: You have to give it to them.
Dr. Tore Curstedt, MD: We had to give it to the others. This is the only clinical trial with a control group and a surfactant group. Then it was not ethical for all—all had to be treated. Then we started with other types: not only give it once, but give it twice, three times, prophylaxis. So we made clinical trials.
But it was impossible to scale up in our hospital laboratory. We had to have a company. Pharmacia was not interested.
Dr. Anton Titov, MD: Still not interested?
Dr. Tore Curstedt, MD: No, they were not interested.
Dr. Anton Titov, MD: The companies should be banging on your door.
Dr. Tore Curstedt, MD: Yeah, but it is such a small product. They said, "In Sweden, how many? Perhaps 300 to 500 in Sweden." But you have the whole Europe, the US, and many others. Then we came in contact with Chiesi Farmaceutici in Parma, a private-owned small company at that time. They were interested.
Dr. Anton Titov, MD: They had incentives to move fast and become bigger.
Dr. Tore Curstedt, MD: Yes, because it is fast, and it was good. Nowadays, it was good that we had Chiesi instead of Pharmacia. It is better to make a bigger product in a small company than a marginal product in a big company.
Dr. Anton Titov, MD: They took the product and managed to scale up the production so it became available, and you probably led that process as well.
Dr. Tore Curstedt, MD: Yes, we have been there many times. Now they can do it there because, in five years, we produced 3,000 to 4,000 vials and saved 3,000 to 4,000 babies—some of them have survived anyway. We have treated today nearly four million preterm babies. For us to make three to four million vials in a hospital, it would have taken us a thousand years. It would have been totally impossible.