Topotarget CUP interim data out

Topotarget A/S (CPH: TOPO) is releasing top-line data from its and Spectrum Pharmaceuticals (NASDAQ: SPPI) drug candidate Belinostat in Open-label Randomized Phase II Trial this morning. In the trial the drug is in given in combination with Carboplatin and Paclitaxel or “BelCaP” and compared to Carboplatin and Paclitaxel chemotherapy alone in previously untreated patients diagnosed the Carcinoma of Unknown Primary or CUP. The trial has been fully Topotarget sponsored and run with Progression Free Survival measured by RECIST criteria as the primary endpoint.

Topotarget reportedly decided to make the cut-off after the events were happening slower than hypothesized based on typical disease prognosis. The total enrolment was 89 patients and the cut-off for interim analysis was understood by the investors to happen after 68 PFS events. The drug was given as IV infusion and orally. Across many Nordic stock exchange discussion boards, Topotarget has become the most discussed stock despite its rather miniscule valuation of less than 70 million Euros at market close yesterday. Many investors appeared to have extremely high hopes going into the data and were taking a major portfolio risk in their allocation at least according to their own words.

The top-line data released today shows that the trial did not meet the high primary endpoint of 60% PFS improvement. In the secondary endpoint of overall response rate, BelCap arm in the intent to treat analysis showed statistically significant benefit at 5% confidence level of 43.2% vs. 22.2% ORR (p-value of 0.025). The overall survival curve indicates a separation in BelCaP’s favour from eight months forward.

There is a conference call at 11.30 AM (CET), where more details are expected. It would have been preferable to have more colour on the results already in the release. It is perhaps likely, that the initial market reaction is one-off disappointment although one must keep in mind the low valuation and upcoming PTCL catalyst as well as the low statistical powering of this Phase 2 study as well as the heterogenity of the disease warranting closer analysis.

***UPDATE***

Topotarget started the day heavily in the minus as panic ensued. Going into the conference call, the stock had pared majority of the 50% decline but again slid as presentation slides became available. The difference in primary endpoint PFS was almost non-existant. Also thus far there is no statistically significant overall survival benefit to be shown, although there is some divergence from 8 months onwards, but that is nowhere near statistical significance and even if it were, the significance of such a matter would be debatable. BelCaP was mostly well tolerated but there was a greater incidence of grade 3/4 adverse events (25 vs. 19). The said comments about PFS events happening slower than expected is also not evident from the graphs.