Karyopharm: Opportunity To Buy Based On Latest Endometrial Cancer Data And Xpovio Sales Estimates

Feb. 19, 2022 4:53 AM ETKaryopharm Therapeutics Inc. (KPTI)11 Comments7 Likes

Summary

  • Primary endpoint of phase 3 SIENDO study met in which a statistically significant improvement of progression-free survival was observed in patients treated with selinexor over placebo.
  • NDA filing of selinexor as a maintenance therapy for patients with advanced or recurrent endometrial cancer expected in the 1st half of 2022.
  • Full-year 2022 XPOVIO sales were guided higher of between $135 and $145 million. This 2022 estimate is higher compared to full-year 2021 sales of XPOVIO which only reached $98.4 million.
  • CHMP opinion on selinexor in combination with Velcade and low-dose dexamethasone for the treatment of patients with multiple myeloma expected in 1st half of 2022.
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Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a good biotech to own for the long term. The stock took a tumble after it released results from its late-stage SIENDO study using selinexor for the treatment of patients with advanced or recurrent endometrial cancer. The stock has recovered since then, but I believe that it has more room for gains. That's because it will meet with the FDA to discuss the data. The study still reached statistical significance and so that means there is a high probability that it will be able to file an NDA for selinexor for the treatment of patients with advanced or recurrent endometrial cancer. Even then, if one makes the other side of an argument, there was a sub-group of endometrial cancer patients who responded with an even better response. This was observed in patients with the wild-type p53 mutation. The data observed in this subgroup far exceeds that which was observed in the entire group as a whole. Regardless, Karyopharm can move forward with FDA approval of selinexor for the entire population in my opinion. Having said that, the reason why I think the stock can trade higher is based on two catalysts that investors can look forward to. The first catalyst would be the full data set from the SIENDO study, which is expected at an upcoming medical meeting. The second catalyst would be the NDA filing itself of selinexor for the treatment of patients with advanced or recurrent endometrial cancer. This regulatory filing to the FDA is expected in the 1st half of 2022.

Statistical Significance Achieved In Two Areas In Patients With Advanced Or Recurrent Endometrial Cancer

Karyopharm shares had dropped considerably to a low of $8.19 per share when it had released results from its phase 3 SIENDO study. This was the study which was exploring selinexor for the treatment of patients with advanced or recurrent endometrial cancer. Endometrial cancer begins in the uterus. Specifically, it starts off in the layer of the cells that form the lining of the uterus. The uterus is the pear-shaped pelvic organ where fetal development occurs. There are two types of endometrial cancer, which are:

  • Type 1
  • Type 2

Type 1 endometrial cancer is the one that grows slowly. On the other hand, type 2 is not as common and grows rapidly. Not only does it grow in a rapid fashion, but spreads to other organs in the body. This type of cancer tends to happen in women after the age of 55. There are several symptoms that these patients experience which are:

  • Bleeding after menopause
  • Abnormal vaginal bleeding occurring
  • Bleeding between periods
  • Pain in the pelvis

Despite all these symptoms, it can also be possible that a woman with endometrial cancer experiences no symptoms at all. It is said that there are more than 200,000 cases of this cancer in the United States each year.

The results of the phase 3 SIENDO study were positive. For this late-stage study a total of 263 patients with stage IV or recurrent disease who had a partial or complete response after 12 weeks of standard of care taxane-platinum combination chemotherapy. Patients were randomized 2:1 to receive either maintenance therapy of 80 mg of selinexor once a week or placebo until disease progression occurs. The primary endpoint of this study was to achieve a statistically significant improvement in progression-free survival (PFS) compared to placebo. The primary endpoint of the study was met in that those who took selinexor achieved a median PFS of 5.7 months, as opposed to those who took placebo who only achieved a median PFS of 3.8 months. The primary endpoint met with statistical significance with a p-value of p=0.0486. Now, the stock may have traded lower on release day because of an opposing argument whereby the p-value was right on the line of statistical significance. The way I view it as long as the primary endpoint is met with statistical significance, it doesn't matter how close to the line it is. The FDA only cares that the study reaches the primary endpoint and in this case that's exactly what Karyopharm did.

Even if you put aside the stat sig data above, there is a second reason why the SIENDO data is good. This data came from advanced or recurrent endometrial cancer patients who had the wild-type p53 mutation. It was noted that patients who took selinexor achieved a statistically significant reduction in the risk of disease progression or death with a p-value of p=0.0006. As you can see, this was a really good number in terms of statistical significance. Both the wild-type p53 subgroup and entire group of patients are important. However, in my eyes I view the patients with wild-type p53 mutation as being a more important population to treat. Why do I believe this to be the case? Well, for starters those with accumulation of the p53 protein have a far worse prognosis of their cancer. That's because p53 allows the tumor to achieve better suppression against treatments. In the case with this subgroup of patients, selinexor performed far better than the entire group. The breakdown in terms of median PFS is as follows:

  • Selinexor treated patients - median PFS of 13.7 months
  • Placebo treated patients - median PFS of 3.7 months

This gives a reduction in the risk of disease progression of death of 62% for patients who took selinexor.

Believe it or not, but there is a third argument to make the case for these results as being good. It is that the use of selinexor was given to patients who had already responded to platinum-based chemotherapy. In other words, the use of selinexor will be given for maintenance. Patients will still first receive standard of care (SOC) platinum-based chemotherapy, but selinexor is being used as a maintenance therapy for advanced or recurrent endometrial cancer patients. But why is this statement important to the FDA or for these patients for that matter? It is because if selinexor is approved by the FDA it would be the first and only maintenance therapy for this patient population following response to chemotherapy. In other words, at the moment there is no maintenance treatment approved for use after SOC platinum-based chemotherapy for these patients. That means after patients take SOC they go into a wait and see if recurrence occurs mode. With selinexor being approved, it would remove this approach. I would very much think the FDA would be keen on providing patients with some type of therapy, rather than a "wait and see" approach.

Catalyst Opportunities To Keep An Eye On That Could Push Stock To Trade Higher

The stock has recovered since it released its results from the phase 3 SIENDO study a few weeks ago. It dipped to stock price of $8.19 per share and has since been trading above $14 per share. I believe that additional gains are possible. Why? Because of the two catalyst opportunities I noted above. The first of which is that Karyopharm intends to submit a supplemental New Drug Application (sNDA) to the FDA in the 1st half of 2022 for selinexor for the treatment of patients with advanced or recurrent endometrial cancer. Not only that, but only the top-line data was shown in the most recent release of the SIENDO data. The company intends to present full results from this late-stage study at an upcoming medical conference in the 1st half of 2022. Lastly, there is a 3rd catalyst worth mentioning. The Committee for Medicinal Products for Human Use is expected to issue an opinion in the 1st half of 2022 for the Marketing Authorization Application (MAA) for selinexor in combination with Velcade (bortezomib) and low-dose dexamethasone for the treatment of patients with multiple myeloma (MM) following at least one prior therapy.

Financials

According to the 8-K SEC filing, Karyopharm Therapeutics had cash, cash equivalents, restricted cash and investments of $235.6 million as of December 31, 2021. The thing is that this biotech is a good long-term to own because XPOVIO (selinexor) has already been approved in the U.S. for several oncology indications, which are:

  • Selinexor in combination with Velcade and dexamethasone in patients with MM after at least one prior therapy
  • Selinexor in combination with dexamethasone in patients with heavily pre-treated MM
  • Selinexor in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma after at least 2 prior lines of systemic therapy

Selinexor has also been approved in several other territories as well such as: Europe, China, United Kingdom, South Korea and Israel. I mention all this, because XPOVIO has been selling well. In the most recently reported Q4 2021 earnings, the biotech noted that U.S. net product revenues of XPOVIO was $29.8 million, which was up 47% year over year. Not only that, but the company even guided higher for full-year 2022 XPOVIO revenue. It states that full year 2022 revenue for the drug is estimated to be around $135 million to $145 million. If this guidance is achieved, it will be way above XPOVIO full-year 2021 revenue which ended up being $98.4 million. Based on existing cash on hand, sales of XPOVIO and license agreements, Karyopharm believes that it has enough to fund its operations into early 2024.

Risks To Business

There are several risk factors that investors should be aware of when investing in Karyopharm. I would say that the data set looks good from what has been released so far from the SIENDO study. However, there is no guarantee that the FDA will accept the sNDA of selinexor for the treatment of patients with advanced or recurrent endometrial cancer. In the off chance that the FDA doesn't like the data set for the entire population, Karyopharm's selinexor performed exceedingly well in the patients who had the wild-type p53 mutation. In a worst case scenario, I can see selinexor being approved for that specific sub-population. However, since the primary endpoint was met with statistical significance in both populations, I think the biotech will be good to achieve regulatory approvals for both. The second risk would be in terms of revenues for XPOVIO. The company guided higher for full-year 2022 sales, but there is no guarantee that such sales will be achieved. If there is a quarter that doesn't perform as well as it should in terms of XPOVIO sales, there is a chance the stock could trade much lower.

Conclusion

Karyopharm Therapeutics is a good long-term biotech to own. I believe that it has been doing quite well in terms of sales with XPOVIO. That's because in 2021 it ended with $98.4 million in revenue, however, for the full-year 2022 it expects revenue between $135 million to $145 million. The fact that it guided that much higher revenue for the year bodes well for when it reports in the coming quarters. This is just if you factor in the revenue it generates with XPOVIO. The other positives will come from the three catalysts which are going to be released in the 1st half of 2022. This will be the NDA filing of selinexor for the treatment of patients with advanced or recurrent endometrial cancer. Secondly, the full data set from the SIENDO study which is expected at an upcoming medical meeting. Lastly, you have CHMP opinion for selinexor to be approved in the European Union. This would be potential regulatory approval in the European territory of selinexor in combination with Velcade and low-dose dexamethasone for the treatment of patients with multiple myeloma (MM) following at least one prior therapy. There is one other aspect to consider as well for this pharma company. It has a pipeline that is focused on several key indications. This includes the potential of possibly expanding the use of selinexor for the treatment of patients with MM, myelodysplastic syndrome (MDS) and myelofibrosis. The goal is to improve survival for these cancer indications. Another factor is to use selinexor against several solid tumor malignancies. The SIENDO study was good in that Karyopharm established that selinexor can also perform well in solid tumor malignancies. Other solid tumor malignancies being explored in the pipeline are: Non-small cell lung cancer (NSCLC), melanoma, Glioblastoma and colorectal cancer. Based on increased sales guidance of XPOVIO, statistically significant data from SIENDO, plus additional indications in the pipeline, I view Karyopharm Therapeutics as a solid long-term buy.

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