Summary
- Safety profile of XPOVIO is not satisfactory.
- The primary endpoint in the STORM trial is weak and the measured efficacy benefit is also modest.
- Certain other risks also have to be considered for Karyopharm Therapeutics.
- There, however, remains a small probability of positive outcomes for Karyopharm Therapeutics.
Lately, Karyopharm Therapeutics (KPTI) has been one of the top trending tickers in the healthcare industry. The stock is up by 55.65% since July 1. Ironically, the stock is down by 5.98% in 2019 YTD. Still, this has not reduced the overall interest in the stock, from investors as well as analysts.
Karyopharm Therapeutics soared on July 3, after the company announced FDA accelerated approval for the first and only nuclear export inhibitor, XPOVIO (selinexor) in combination with dexamethasone for Penta relapsed or refractory MM (multiple myeloma) patients. On the same day, the company’s stock jumped by 36.03% and closed at $8.90.
A favorable regulatory decision can be game-changing for a clinical-stage biopharmaceutical company. However, that applies when the regulatory decision translates into revenue potential. Unfortunately, I do not see this happening for Karyopharm Therapeutics.
In this article, I will explain why I believe Selinexor may not be a blockbuster therapy. Since this is the only lead asset of the company, its fate is closely tied to Karyopharm Therapeutics. Hence, I will explain my hypothesis for staying away from Karyopharm Therapeutics in July 2019.
Xpovio’s toxicity is high, especially considering the very ill target population.
According to Karyopharm Therapeutics’ investor presentation, the current FDA approved indication of XPOVIO enables the drug to target around 6,000 MM patients in the U.S., who are currently in fourth-line plus setting. Hence, it should be remembered that Selinexor is mainly targeting a very sick patient population, where the disease has progressed despite four previous therapies.
The FDA approval of Selinexor was based on Phase 2b STORM trial. As shown above, it was seen that the fatality in the trial was 8.9%, which is unusually high considering that STORM was a single-arm, open-label trial. Results from blinded, randomized, control trials are generally better predictors of the drug’s real-world safety profile. However, here we do not have this data.
The incidence of severe adverse events such as thrombocytopenia, neutropenia, hyponatremia was unusually high in patients treated with Selinexor. It was seen that 74% of patients suffered from thrombocytopenia, while 61% suffered from Grade 3-4 thrombocytopenia. Around 34% of patients suffered from Neutropenia, while 21% suffered from Grade 3-4 neutropenia. All tested patients suffered from gastrointestinal toxicities. Nausea was reported in 72% of patients, and Grade 3 nausea in 9% of patients. Diarrhea was reported in 44% patients and Grade 3 diarrhea in 6% of patients. Anorexia was reported in 53% patients and Grade 3 anorexia in 5% of patients. Hyponatremia was reported in 39% patients, while Grade 3 or 4 hyponatremia in 22% patients. 52% of patients experienced any grade of infection. Upper respiratory tract infection of any grade occurred in 21% of patients, pneumonia in 13% patients, and sepsis in 6% of patients. Grade ?3 infections were reported in 25% of patients. Neurological toxicities were seen in 30% of patients, and Grade 3- 4 toxicity was seen in 9% of patients.
Subsequently, we see that 27% of patients discontinued the treatment, 53% had to reduce dosage, and a whopping 65.3% interrupted therapy.
I can draw parallels here with Puma Biotechnology’s extended adjuvant breast cancer therapy, NERLYNX. Previously considered to be a very high potential drug, patients have been increasingly discontinuing therapy due to side-effects, prominently diarrhea. The company’s share price has fallen by 52.14% in 2019 YTD.
It can be argued that patients are much less desperate for treatment options in the extended adjunctive setting as compared to fourth-line plus setting. However, it should also be remembered that patients in the fourth line plus setting are in an extremely delicate situation. Hence, the majority of physicians will not initiate or continue with therapy with significant side-effects, unless there is no proof of survival benefit.
