NVSEF - Ionis: Potential Advancement Into HAE Space Makes This A Must Watch

2023-06-20 06:58:24 ET

Summary

• Ionis Pharmaceuticals' phase 2 study showed that patients treated with donidalorsen through week 17 achieved a 90% reduction in hereditary angioedema attack compared to placebo; the second dose brought a 97% reduction.
• Clinical trial results from the phase 3 OASIS-HAE study, using donidalorsen for the prevention of hereditary angioedema attacks, are expected to be released in the 1st half of 2024.
• The global hereditary angioedema treatment market size is projected to reach $6.53 billion by the end of 2025.
• A PDUFA date of December 22, 2023, has been established, whereby the FDA will decide whether or not it will approve eplontersen for the treatment of patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy.

Ionis Pharmaceuticals ( IONS ) is a good speculative biotech play to look into. That's because it has a very solid program in progress, which is using donidalorsen for the prevention of hereditary angioedema [HAE] attacks. Thus far, a phase 2 open-label study has shown this drug to be able to consistently reduce HAE attacks in a sustained fashion. A major catalyst opportunity for traders/investors exists here, because topline results from an ongoing phase 3 study using this drug to treat this patient population, are expected to be released in the 1st half of 2024. As I will explain below, the market opportunity for HAE is huge and if Ionis announces positive phase 3 results in the first part of 2024, then I believe it could cause the stock to trade higher. While this catalyst won't take place immediately, that doesn't mean that there aren't other catalysts for which traders/investors could capitalize on.

For instance, it has a PDUFA date of December 22, 2023, whereby the FDA will decide whether or not it will approve eplontersen for the treatment of patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy [ATTRv-PN]. Another catalyst is also expected in the 2nd half of 2023, which would be the release of results from a phase 3 study using olezarsen for the treatment of patients with Familial chylomicronemia syndrome [FCS]. Should this study succeed, then this could be the first independent commercial launch for Ionis Pharmaceuticals. Lastly, it was able to receive FDA Accelerated Approval of QALSODY, which was approved for patients with amyotrophic lateral sclerosis [ALS] who have the SOD-1 genetic mutation. The marketing Authorization Application [MAA] of this drug was accepted by the European Union and is under review. The potential to expand into the large HAE treatment market, plus several other catalysts expected along the way in 2023, are reasons why I believe that Ionis Pharmaceuticals is a good speculative biotech play to look into.

Donidalorsen For The Prevention Of Hereditary Angioedema Attacks

Ionis should be watched closely because it is advancing a drug for the prevention of Hereditary Angioedema attacks. Hereditary Angioedema [HAE] is a rare inherited disorder whereby recurrent episodes of accumulation of fluids outside the blood vessels occur. Why is this an issue? That's because such accumulation of fluids causes normal blood flow to be blocked, which in turn results in rapid swelling in several parts of a person's body. Such body parts which can be affected are: Feet, limbs, hands, airway and intestinal tract. As I stated above, the whole premise of this article is Ionis' ability to achieve clinical success in being able to target this large HAE market. Why do I say that? That's because the global hereditary angioedema treatment market size is projected to reach $6.53 billion by the end of 2025 . There are several symptoms that these patients might experience, but there is one key fact to make note of, Which is that it highly depends on where the HAE attack actually occurs. For instance, if an HAE attack occurs in the intestinal tract, then symptoms would include: Stomach pain, vomiting and nausea. However, if such an attack occurs in the airway, then it can restrict breathing instead. However, it is said that about one-third of people with this rare inherited disorder have a non-itchy rash that forms called erythema during an attack.

As I stated at the beginning above, Ionis has a good shot at being able to target this large HAE market space because of what it has been able to achieve in a phase 2 open-label study. Such a study showed that patients given 80 mg of donidalorsen through week 17, achieved a 90% reduction of angioedema attacks compared to placebo after the first dose. Not bad, right? Well, it got even better as patients were then treated with a second dose. With a second dose of donidalorsen, there was a 97% reduction in angioedema attacks. It is good when a drug is able to achieve such great clinical efficacy when it is measured as a result of the primary endpoint [Ability to reduce HAE attacks]. What's even more profound is that there was a statistically significant improvement in quality of life. Such an improvement was measured with the Angioedema Quality Of Life Questionnaire [AE-QoL]. I believe that this questionnaire if highly important because it asks how patients feel after having gone through treatment with donidalorsen. Of course, the reduction of HAE attacks is important with respect to regulatory approval and patient improvement, but at the end of the day it's how the patient feels after being given such a treatment. Besides the efficacy I provided above, treatment with donidalorsen continues to be safe and tolerable for the patients who are taking it.

While this phase 2 study was able to establish proof of concept that donidalorsen is capable of being able to prevent HAE attacks , this trial alone won't be enough for Ionis to seek FDA approval of this drug for this patient population. This is where the phase 3 OASIS-HAE study comes into play. This late-stage registrational study was initiated back in November of 2021 . It is a double-blind, randomized, placebo-controlled study that recruited a total of 84 patients with Type 1 and 2 hereditary angioedema [HAE]. Patients were randomized to receive monthly or bi-monthly subcutaneous doses of donidalorsen for a total of 25 weeks. This study is progressing quite well because enrollment for it has already been completed. Having said that, this sets up a major catalyst opportunity for traders/investors to look forward to. It is expected that results from this phase 3 OASIS-HAE study, using donidalorsen for the treatment of Type1 and Type 2 HAE patients, will be released in the 1st half of 2024.

Financials

According to the 10-Q SEC Filing , Ionis Pharmaceuticals had cash, cash equivalents and short-term investments of $2.3 billion as of March 31, 2023. A big reason for the cash on hand is because back in January of 2023 it received $500 million from Royalty Pharma. The reason why Ionis received this amount is because of a deal that was made by both companies with respect to a royalties agreement deal for Biogen ( BIIB ) SPINRAZA and Novartis ( NVS ) pelacarsen. On top of the $500 million Ionis received in January of 2023 , it will also be eligible to receive up to $625 million in additional pelacarsen milestone payments.

The premise of this company is that it receives half its revenue from commercial product sales and then the other half from numerous partnered programs. Commercial sales in Q1 of 2023 were $50 million for Ionis, which relates to SPINRAZA royalties. There is a chance for Ionis to get away from only commercializing partnered products on the market. How so? That's because it has a few clinical products in its pipeline which are wholly-owned ones that are being advanced. For instance, should donidalorsen succeed in phase 3 testing and be approved by the FDA, then all sales would belong to Ionis. Another candidate, by the name of olezarsen for the treatment of patients with FCS, would possibly be the first independent commercial launch should it make it to the market. Again, this is another opportunity for it to obtain full commercial sales of its wholly-owned clinical product, instead of having to pay out royalties to a partner.

Risks To Business

There are several risks that traders/investors should be aware of before investing in Ionis Pharmaceuticals. The first risk to consider would be with respect to the ongoing phase 3 OASIS-HAE registrational study, which is using donidalorsen for the prevention of HAE attacks. Results from this late-stage study are expected to be released in the 1st half of 2024. While the phase 2 open-label study was able to establish proof of concept of this drug being able to reduce HAE attacks with statistical significance compared to placebo, there is no guarantee that the same outcome will be achieved in the phase 3 OASIS-HAE registrational study when trial results are released. A second risk to consider would be with respect to the December 22, 2023 PDUFA date of December 22, 2023, whereby the FDA will determine whether or not it will approve eplontersen for the treatment of patients with ATTRv-PN.

There is no assurance that the FDA will approve this regulatory application in its current form. A third risk to consider would be with respect to the ongoing phase 3 study, which is using olezarsen for the treatment of patients with familial chylomicronemia syndrome [FCS]. Results from this study are expected to be released in the 2nd half of 2023. If the primary endpoint of this trial is not met with statistical significance, then Ionis won't be able to file for FDA approval of olezarsen for the treatment of this patient population thereafter. A final risk to consider would be with respect to the ongoing Marketing Authorization Application [MAA] review of QALSODY. While the FDA granted this drug Accelerated Approval for the treatment of ALS patients with the SOD-1 mutation, there is no guarantee that the European Union will also decide to approve this drug.

Conclusion

The final conclusion is that Ionis Pharmaceuticals is a good speculative biotech play to look into. That's because with the use of its drug donidalrosen it has the ability to tap into a very large market opportunity. As I stated above, the global hereditary angioedema treatment market size is projected to reach $6.53 billion by the end of 2025. Even though results from the phase 3 OASIS-HAE study are not expected to be released by the 1st half of 2024, there are still many other catalysts for investors to look forward to along the way. For instance, a PDUFA date is expected at the end of this year on December 22, 2023, whereby the FDA will decide whether or not it will approve eplontersen for the treatment of patients with ATTRv-PN.

Then, you have the ability for this pharmaceutical company to be able to expand its approval presence with the ongoing European Medicines Agency [EMAM] review of QALSODY for the treatment of patients with ALS who have the SOD-1 genetic mutation. Lastly, you have the release of results from a phase 3 study that is using olezarsen for the treatment of patients with familial chylomicronemia syndrome [FCS]. I consider this to be a crucial readout for this company. Why is that? That's because should this drug succeed in the ongoing late-stage clinical trial, along with FDA approval, then it would be the first drug to be commercialized which is wholly owned by Ionis. Up to now, it has had to split commercial sales with a partner. It would be nice for it to be able to receive regulatory approval for a clinical product where it doesn't have to split any of its sales profit. With potential to expand into the large HAE treatment market, plus several other catalysts expected along the way in 2023, I believe that Ionis Pharmaceuticals is a good speculative biotech play to look into.

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