Milestone Pharmaceuticals: Potential NDA Submission Of Etripamil

Milestone Pharmaceuticals (NASDAQ:MIST) is a great speculative biotech play to look into. It is because one indication in the pipeline has been somewhat de-risked. This involves the use of a nasal spray drug known as Etripamil, which succeeded in meeting the primary endpoint of a phase 3 study treating patients with paroxysmal supraventricular tachycardia (PSVT). Such a drug is kind of important, should it ultimately be approved by the FDA, because it would reduce Emergency Room Hospital Visits. Speaking of the FDA, Milestone now plans to submit the New Drug Application (NDA) to the FDA in the 1st half of 2023, so that it could possibly receive FDA approval of this nasal spray drug thereafter. I wouldn’t say that such an FDA approval would happen that quickly, because the review would take roughly one-year. However, the only hurdle left now is to obtain FDA approval of Etripamil for the treatment of patients with PSVT. It even has a partner already established in an attempt to get this drug approved in the Greater China Territory as well. If it can obtain regulatory approval of this drug in several territories it could eventually expand its market share. In addition, it has another shot on goal using Etripamil for the treatment of patients with atrial fibrillation.

Etripamil For The Treatment Of Patients With PSVT

The most important program in the pipeline to go over involves the use of a nasal spray drug known as Etripamil. The reason why is because it has just been greatly de-risked in the pipeline as I noted above. Again, it is because the drug beat out placebo in the phase 3 RAPID Study against placebo, in patients with paroxysmal supraventricular tachycardia. Paroxysmal supraventricular tachycardia (PSVT) is a disorder characterized by which a faster than normal heart rate occurs. It is important to note that it happens slightly above the heart’s two lower chambers. In other words, it causes rapid heartbeat for the person in question. What makes it a terrible disorder is that it causes symptoms, but then other times it doesn’t cause any at all. In the case of not causing any symptoms, it may be difficult to diagnose. Such symptoms that may occur due to paroxysmal supraventricular tachycardia are as follows:

• Very rapid heartbeat (Consider 100 beats or more per minute)
• Fatigue
• Shortness of breath
• Dizziness
• Fainting
• Chest Pain
• Several Other symptoms as well

The market opportunity for Milestone Pharmaceuticals exists and I say that because it is said that about 2 million Americans have this disorder. Remember above where I said that Etripamil holds potential to change the scope of treatment for these patients? It is because Etripamil is a carry nasal spray which can be self-administered. The only other way to stop PSVT is adenosine, beta-blockers and channel blockers (given intravenously). Sounds good right? It does, but consider that these drugs can only be given under medical supervision like in an emergency department or other hospital type setting. This means should this biotech get Etripamil approved for PSVT, it would allow patients rapid at home treatment without the need to go to the extreme of going to the emergency room or other setting. It is important to note that PSVT is only life threatening when a patient has other heart diseases. On the flip side, PSVT in rare circumstances can cause cardiac arrest.

As I stated in the beginning of this article, Milestone Pharmaceuticals ran a large phase 3 randomized, double-blind placebo-controlled study known as RAPID. There were a total of 706 patients enrolled in this study across North America and European territories. Patients were randomized 1:1 to receive either Etripamil nasal spray or placebo without any type of medical monitoring. In order to keep the study safe, patients who did not respond to Etripamil (achieve symptom relief) were told to self-administer a repeat dose of the drug. It was revealed that this late-stage RAPID trial ended up achieving the primary endpoint of the study with statistical significance. That is, patients who took Etripamil ended up achieving the primary endpoint of time to PSVT conversion. In essence, the nasal spray drug from Milestone Pharmaceuticals was able to beat out placebo with statistical significance. This effect can be observed with the following numbers:

• Etripamil treated patients who converted from PSVT in 30 minutes – About 64.3% of patients
• Placebo treated patients who converted from PSVT in 30 minutes – About 31.2% of patients

Not only that, but there was another solid finding to consider as well. It was also shown that these PSVT patients who took Etripamil also achieved average time to conversion 3X faster than those who took placebo. In other words, the patients given drug achieved quicker symptom relief compared to those who didn’t take it. The adverse events (AES) of the study to note dealt with the nasal administration site. However, the breakdown is not that bad. The Randomized treatment emergent adverse events (RTEAES) were as follows:

This is not bad at all, but I wouldn’t look at this as being a major issue. Why is that? Well, it is because there were no reported serious adverse events (SAEs). This is very good, as I would only worry about the safety of nasal spray Etripamil if there were SAEs noted in this study, which there weren’t.

Okay so the phase 3 study went very well, as I showed you above, the primary endpoint of the RAPID trial was met with statistical significance. However, this is not the only thing to be sent as a package for the possible New Drug Application (NDA) to the FDA which is expected at least by mid-2023. What do I mean? That is, there is additional statistically significant data that was achieved in a prior study using Etripamil for the treatment of patients with PSVT. This was a phase 3 open-label extension study known as NODE-302. The goal of this study was to treat PSVT patients with a self administered 70 mg dose of Etripamil over an extended period of time. Out of the 188 episodes, it was noted that the PSVT conversion rate at 30 minutes for Etripamil treatment was 60.2%. This kind of aligns with the primary endpoint of the phase 3 RAPID study I highlight above. Not only that, but this NODE-302 study achieved another positive finding for these patients taking this nasal spray drug. That is, the need to go to the emergency room to stop PSVT episodes was low 13% of the total patients. Again, the NDA to be filed with the FDA is going to include both the RAPID and NODE-302 studies. I want to point out though that there is no guarantee that these studies will be enough. Milestone Pharmaceuticals is waiting for FDA feedback on whether or not it can file an NDA for Etripamil for PSVT with the current data. If it can, then it expects to do so in mid-2023. The good news is that it has another ongoing open-label study, known as NODE-303, which is a safety study. It remains to be seen if this adds additional findings on the efficacy front, but at least it will add to the safety findings should it turn out to be the same observed in other studies.

Financials

According to the 10-Q SEC Filing, Milestone Pharmaceuticals had $86.2 million in cash, cash equivalents, and short-term investments as of June 30, 2022. It has the ability to continue to raise cash using pre-funded warrants. That is because as of the June 30th 2022 date, it also has 12.3 million common shares of pre-funded warrants outstanding issuable upon exercise. It believes it has enough cash to fund its operations until at least the 2nd half of 2023. I think it will use the pre-funded warrants above, but I wouldn’t rule out the possibility of it also using other means to raise cash. The reason why is because if things go well on the FDA front with the NDA of Etripamil, then it expects its expenses will likely increase. Regardless, I think it won’t wait until the 2nd half of 2023 to raise cash. As such, I would expect another cash raise at least by the 1st half of 2023.

Risks To Business

There are several risk factors that investors/traders should be aware of. The biggest risk to consider is with respect to the FDA. For starters, the NDA of Etripamil for PSVT is only expected to be submitted in the mid-2023 pending positive agency feedback. That is, it will first meet with the FDA to determine if the phase 3 RAPID study (where primary endpoint was met) plus NODE-302 studies are enough for it to be able to file for regulatory approval of the drug in the United States. Being that the primary endpoint of the phase 3 RAPID study was met, I believe there is a good chance of this happening. Secondly, even if the NDA of Etripamil is submitted in mid-2023 there is no guarantee that the FDA will ultimately approve the drug for marketing. Another risk to consider would be with respect to the other indication in which Etripamil is being evaluated for and that is for atrial fibrillation with rapid ventricular rate (AFib-RVR). This is being explored in a phase 2 proof of concept study and there is no guarantee that it will be able to achieve positive results from it. The final risk to consider would be with respect to the financing. As I stated above, it has enough cash to fund its operations until the 2nd half of 2023. As such, I believe that it will likely have to raise cash in the 1st half of 2023.

Conclusion

Milestone Pharmaceuticals is a great speculative biotech to look into. I believe it has potential to do well, because of it meeting the primary endpoint in the phase 3 RAPID study using Etripamil in patients with PSVT. All that remains now is to see if the FDA will allow it to file for approval of this drug for this patient population based on both the RAPID and NODE-302 studies. It does have a safety study it is running, but again I would expect it to show some efficacy, but I don’t know if the FDA will also require this for the filing as well. The opportunity to get this drug approved for this indication in the United States is huge, especially considering that there are about 2 million people in the United States who have PSVT. That’s not all either, as I noted above, there is an opportunity to also target the large greater China region as well. It has already established a partnership with Ji Xing Pharmaceuticals Limited to help possibly get Etripamil approved for this region as well. A phase 3 study was just initiated a few months ago and now all that remains to be seen, is if the primary endpoint in the China region is met as well in this PSVT population. While the pipeline is not huge, there is another indication which the company is exploring. This involves an ongoing phase 2 study using Etripamil for the treatment of patients with atrial fibrillation (AFIB). Hopefully, the biotech can expand to this indication, because it is double the size of the PSVT patient population. AFIB currently affects about 5 million patients in the United States, which is huge. However, the Centers for Disease Control expects the number to increase to 12 million patients within the next 10 years. With a few catalysts in play, plus potential to target another large market, these are the reasons why I believe Milestone Pharmaceuticals is a great speculative biotech to look into.