Monica Gadelha, PhD, Professor of Medicine at the University of Rio De Janeiro discusses the use of paltusotine in patients with acromegaly.
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GH is secreted, controlled by somatostatin. Somatostatin is a molecule that produces the hypothalamus that is above the pituitary. There are drugs that are called somatostatin receptor ligands. These drugs act like they were somatostatin, so they block GH secretion, and they can control the size of the tumor or even decrease the tumor. This is a class of drugs that we call first-generation somatostatin receptor ligands or agonists. The ones that we use now is octreotide LAR and lanreotide autogel both in Brazil. In the US, there is also oral octreotide.
But in the vast majority of the world there is octreotide LAR, lanreotide autogel that we call SST2 agonists. These drugs will block GH secretion and control the tumor. The problem with these drugs is that they are injectable, and they are painful. The patient has to go to the healthcare unit every month to get the shot because this is not a simple shot. It has to be done by a specialized healthcare profession. At the end of the period of the injection, some patients before the next one, complain about relapse of some symptoms as headache is very common.
There is a very nice French study that shows that IGF-1 is not stable with the injections during the whole month. We have all these problems with injections. The problem with acromegaly is that these patients will have to take these medications probably for the rest of their lives, for 30 or 40 years. If they needed these drugs for only six months, that’s okay, that they had to go to the hospital for six months, but it’s for the rest of their life. An oral drug that they can take at home is very expected by the patients.
Paltusotine is an oral medication that binds to this same receptor that is called SST2. An important difference from the other oral, that’s oral octreotide that was launched in US, is that oral octreotide must be taken twice a day. This is complicated because we know that the many patients forget. The one in the morning when the patient has to take as soon as the patient wakes up, it’s okay. But the second one, sometimes the patient is at dinner, out of the house, or at work. So, it’s more complicated. The oral octreotide needs fasting. A second fasting is difficult. Paltusotine is once daily, oral, and very stable drug. In terms of I would say, posology is very convenient for the patient.
Regarding efficacy, we had good data in the Phase II study, but now the first Phase III study, that’s PATHFNDER-1, has finished and the efficacy was demonstrated because in this trial we included the control of the patients on octreotide or lanreotide. I mean, the patients had normal IGF-1 on one of the injectable medications, and they were randomized to receive paltusotine or placebo, so 30 to paltusotine and 28 to placebo. They were treated with paltusotine for 36 weeks.
At the end of this core phase of the study, it was compared the percentage of patients that maintained control of IGF-1 in the paltusotine group and on the placebo group. The difference was huge, as expected. It was 83% in the paltusotine and 4% in the placebo. The study met its primary endpoint. Additionally, there is an evaluation of the symptoms of the patient through acromegaly symptoms diary. Again, the paltusotine maintain the control of the symptoms of the patients. Biochemically effective, maintains the symptoms.
In terms of tumors, there was no tumor increase. The tumor was stable. Regarding safety, we only saw side effects, very typical of acromegaly or with the class of the drug that is the first-generation somatostatin receptor ligands. I mean abdominal pain, nausea, diarrhea that’s associated with octreotide, lanreotide, paltusotine, all these drugs. I think that the drug has efficacy very close to the injectable one, and it’s safe.
For me, the most interesting thing is that during the study, I was telling other investigations and people that I was very impressed with the patients. Because the patients before having a limited option, I have been very honest, I didn’t know how bad the injections were because we only had that. We scheduled the patient, so please come to the hospital this day to get our shot and we will see you for three months in the outpatient clinic. We didn’t know how bad the injection was. It hurts, it’s painful, the patient lost half a day of work to go to the hospital.
When we start an oral drug, the patients were so happy saying that “Oh, my God. We want to stay in this drug. Please, this is much better. I feel much better.” So, we started to see that patients feel better because of not having the injection and more stable throughout the mouth. This was first told to us, physicians, by the nurses. The nurses came to me to say that. I started asking the patients about this. I was surprised. I knew that an oral drug would be a good option, but I didn’t expect that the patients would be so happy as they are now.
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