Good morning again. I'm joined now by Pascal Besman, Chief Strategy Officer at PharmaMar. PharmaMar is a Madrid-listed oncology company built on marine-derived chemistry. Its lead product is Zepzelca, or lurbinectedin, which is in small cell lung cancer, which was approved last October in the U.S., and in June in Europe as first-line maintenance in combination with atezolizumab. Pascal, thanks for joining us. Start with the company, tell us what PharmaMar is, and where marine-derived chemistry comes into play.
Thank you, and thank you to Chardan for hosting us here, and you for attending. PharmaMar was founded 40 years ago by a gentleman from Galicia on the west coast, or the Atlantic coast of Spain. His family was involved in the commercial fishing business at the time, and he was asked by his dad walking in the woods one day, "What do you want to be when you grow up?" His brother said, "I want to be a fisherman." His father said, "Good news. We've got some boats out there for you."
Our founder said, "I want to be a scientist," which probably knowing this was a while ago, probably got him a slap across the back of the head, and he says, "Why do you want to be that?" Anyway, fast-forward a number of years, he became a PhD in chemistry, and one day he said to his brother, "When you go out fishing next time, I'm coming with, and when the nets go up, whatever comes out, that's mine." He would take whatever would come out to the lab. What would come out? Some shrimp, some rubbish, and some sponges. My example is purely an example. No sponges were hurt in this experiment.
He would take sponges and make a puree out of sponges in the lab, put it into a cell full of well-characterized cancer cells, count the cells after a month. If there were no cells left, sponges have anticancer properties, then we would fractionate, see where in sponges they were. Fast-forward a number of more years, and we've got three approved drugs in the world. Trabectedin, Yondelis is the brand name, which is approved in 80 countries for either soft tissue sarcoma and/or ovarian cancer. Then we have plitidepsin, Aplidin, approved for late stage multiple myeloma, and Zepzelca, or lurbinectedin, that was just mentioned before, approved in 20- odd countries for either relapsed metastatic small cell lung cancer or first-line metastatic small cell lung cancer. T hat's kind of where we've ended up.
We have our own pipeline looking at further of these marine discovered molecules. We have the largest library of them in the world of over 500,000 molecules, and we continue to do marine expeditions. To preempt one of your questions from the field you won't get to ask, where's the best place to go hunting for medical things in the seas? It's around Indonesia, Philippines. D on't ask me why, because we don't know.
It definitely takes an appetite for risk and an appetite for adventure to go looking for natural products, especially in the ocean. Let's move on to your IMforte study. The FDA approved the atezolizumab combination as first line maintenance a year ago. Europe followed in June, and you launched in Germany and Austria over the summer. How is uptake tracking, and what does the European rollout look like from here?
Thanks for that. Yes, you've got all the dates right. In Europe, it's various gates you have to go through. The first thing is what's called the CHMP recommendation. That's from EMA, the European equivalent of FDA. Once you get through that, usually the EU rubber stamps that 70 days later. If you want to be an insomniac, I can explain to you later why 70 days. It's got to do with Brussels bureaucracy and nine different committees having to sign off on it sequentially. Anyway, it's 70 days. After that, theoretically, it's approved for launch in any European country, part of the EU. However, you haven't got reimbursement yet. That's done on a national level. W ait, there's more. In certain countries, you even have to go beyond national to regional levels.
In fact, if you get approved in Europe, you have to print a label right now in 28 different languages, and there aren't 28 countries in the EU. But why is that? Well, for example, Belgium has French and Flemish. In Spain, you have Spanish, Castilian, you got Catalan, and you got Basque. In Spain, for example, each region has to approve the drug for reimbursement as well, so it's a long and tortured process. Y ou can basically launch freely in Germany and Austria day one, which we did. W e're now about three months into that launch in those countries, and we've said previously the launch was going ahead of expectations. Obviously small numbers, and they can vary one week to the next, so I'm not making any predictive statements. A pplying safe harbor here.
We've also said that we expect to have reimbursement in almost all of Europe within one year from its approval. We expect the next countries of significance where we would get those approvals to be France and Spain, hopefully this year, maybe early next, followed by Italy, and then others. So we have almost all of Europe done within the first year of its approval.
We have our issues with our FDA system, but at least it's just one FDA. At least we don't need to go get approvals from every state. Let's move on to talk about tarlatamab. The tarlatamab maintenance data lands at ESMO in just a few days from now. How do you see the competitive picture, and what will you be looking for in the tarlatamab numbers?
Tarlatamab is already approved in Europe in the second-line setting. It's only been launched in Germany and Austria as of yet. It's got a very complex administration profile. It requires the doctors to have access to an ICU. Patients do get cytokine release syndrome and ICANS as well. I'd say most doctors you speak to will say it's a drug that's got very interesting efficacy for an unknown group of patients and is not for every patient, every doctor, every facility. That said, their efficacy can somewhat be described as lottery ticket-like efficacy because the people who do respond very well if they can tolerate it. Obviously I don't have a crystal ball as to what their data is going to show. I can simply refer that Amgen used some aggressive adjectives in their press release announcing it.
I'm presuming the data's good because Amgen is not going to go out on a limb and say the data is spectacular and then present bad data. We are already on the market. As far as we know, they have not filed this yet, so they will probably be around a year or a year plus behind us. Their price is significant. They've used the U.S. price in their launch in Germany. To give you an idea, their U.S. price is 25% higher than our U.S. price, gross to gross. In Europe, they've chosen this very similar price, and our price gross to gross U.S. to Europe is in Germany 50%. They may not launch in all jurisdictions in Europe. They may. That's a question for Amgen.
As far as I'm concerned, I've spent a lot of the last 10 years listening to the patient side of things, and I think when I joined PharmaMar, the standard of care for second line small cell lung cancer was topotecan. Topotecan was approved in 1996, and I only see, I think, three people in this room who were born then. That's a long time ago to not have had any advance, for 25 years for these patients who have a very aggressive malignancy, are told it's because they smoked, so they have smoker's guilt, have very limited options, and a life expectancy of eight months at diagnosis. When we fast-forward to today and what this means for the patient, whether it's tarlatamab, and congratulations to Amgen for what they've done for patients or ourselves, or atezolizumab, or durvalumab, we've got seven more options.
I was talking recently with a doctor at the lung cancer conference in Korea, and I was saying, "Do you remember what a conversation was like with a patient when you came back with their diagnosis of small cell lung cancer?" I said, "Didn't it go something like, 'Yeah, I got bad news and I got worse news, right? You've got small cell lung cancer. Yes, it's because you smoked, and I don't have many options. You're going to lose your hair, and you're not going to live a year. But other than that, pip.'"
Now what you've got is a situation where the doctor is coming in and say, "You've got small cell lung cancer. However, I've got a whole map in my brain of seven, eight drugs that I like to see you have before we get to the end of this. This is going to be a long road that we're going to go through together." Having options equals hope, and having hope equals compliance, and having hope and compliance equals better results. I'm looking forward to seeing their data, and I hope it's as good as many people think it will be.
Talk us through the sequencing argument, the idea that lurbinectedin maintenance followed by tarlatamab in second line gets a patient further than either drug alone. Walk us through that.
The data would show you based on what is in the labels, that lurbinectedin in first line maintenance gives you about 14 months, followed by tarlatamab in second line gives you about another 11. If you just were to add those up, you get to 25. We don't know what the alternative of using tarlatamab in first line maintenance because we haven't seen it, and we don't know what you are going to be using in second line. The problem is topotecan, this drug that was approved before you were all born, is not only barely efficacious, it is also very toxic.
Many patients don't even get the response that the label says they should because they drop out. In terms of comparing it to the individual components alone, we have data for atezolizumab in the maintenance setting. That is what we beat, with the combination with lurbi. We don't have data of lurbinectedin monotherapy in the maintenance setting, however.
Let us talk about your LAGOON study. It did not meet its endpoint back in June, and Jazz has moved to withdraw the second line U.S. indication. Monotherapy arm came in below the control arm on survival. How do you explain that?
I can't explain it cleanly because we've looked at the data and seen if there were imbalances or operational issues or whatever. What I can say is in the 10 years prior to this study readout, there have been about a dozen studies in the same setting using topotecan, and we had an incredibly narrow band of results between 7.8 months and 8.4 months, every single one. All of a sudden, we came in with 10.7, and everyone said, "Something's got to be wrong." Excuse me. Just now in Korea at the meeting I was at, there were two other studies in second line, granted both done in China. Both of them used a lower dose than we use in the West of topotecan, and yet both of them gave us results, one just below 10 months, the other one 10.7 again.
All of a sudden, after a decade being around eight, we're now around 10 in three studies in a row. I asked a doctor or two about that, and I said, "Did something change about how you use topotecan after 35 years?" I said, "I don't think so. Is there better supportive care all of a sudden after 35 years? Don't think that either." Are these just weird outliers, or is this a brave new world? I don't think anybody knows at this point. We tend to have seen upward creep of standards of care over time as supportive care and doctors and nurses learning how to use drugs.
After a decade, to have this quantum 25% leap is very strange. We'll see. In the meantime, the second-line label has been removed by Jazz. They continue to sell in first-line maintenance. We never got the second-line label, so the economic impact for us in Europe will be zero. That's really the end of the topotecan story for us.
We have time for one more question, so let's go a little bit beyond lung cancer. You completed recruitment in your SaLuDo study in first-line leiomyosarcoma in May with a readout guided for the first half of next year. What should we expect from that and from the rest of the pipeline?
This is by far the most advanced part of the pipeline. We should focus on that. Leiomyosarcoma is another ultra-rare disease that has not had an approved drug since doxorubicin, which is even older than topotecan. It is like topotecan's father. It is nicknamed the Red Devil for two main reasons. One, it is red, and two, it acts like a devil. It is the standard of care to this day in first-line leiomyosarcoma, and the only other drug that is meaningfully used is our drug, trabectedin, which is the father of lurbinectedin, based on a French study that showed a significant overall survival benefit and PFS benefit. Since lurbinectedin is an analog of trabectedin, we have tried it in some early stage studies, and now we are in a phase III study, which we expect to beat the control arm.
If so, we would expect very rapid uptake because we have been involved in sarcoma since 2005, our first approval. We know every doctor, every patient, every patient association all across the world. So we are very excited about it. It is a small opportunity, but the number of cycles is about double what we get in small cell lung cancer. So what you lose in the patient numbers, you make up and find their own drug.
W e are looking forward to that readout next year. Pascal, thank you. Please join me in thanking Pascal Besman from PharmaMar.