Stemline patient death becomes secondary investors’ problem

A statement released by Stemline Therapeutics late yesterday amounted to the first official confirmation of a second patient death on a pivotal trial of the group’s lead asset, SL-401. Rumours of the death had been circulating since it occurred two weeks ago.

Beyond the personal tragedy the death causes two immediate problems, firstly calling into question Stemline’s ability to control an adverse event that it had said was manageable via a protocol change. And bankers leading an equity offering announced just one day after the death have now seen Stemline stock fall 40% below the price at which they had underwritten it.

SL-401 comprises a toxin conjugated to an IL-3 domain that targets CD123, and the pivotal study in question aims to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN). The relevant side effect is capillary leak syndrome (CLS), a life-threatening condition where cells lining capillaries separate, allowing leakage of fluid from the circulatory system into the interstitial space.

Problem solved?

On January 10, at its presentation at the JP Morgan conference, Stemline was still able to boast that a protocol modification in the BPDCN study had allowed it to eliminate the CLS problem. In the trial’s first iteration SL-401 caused one patient to die because of CLS, and another to experience grade 4 (ie, very severe) CLS.

“Since implementation of safety precautions in the lead-in severe CLS has not been observed in BPDCN,” the company said. At around this time Stemline was sounding out the market for a $45m secondary equity offering, which it ultimately announced on January 19.

However, by January 19 another BPCDN patient had already died. This patient’s sister contacted EP Vantage on January 27, reporting that the death had occurred after two of five doses of SL-401.

EP Vantage was also directed to a Facebook page detailing the patient’s treatment progress, which claims that she developed CLS in the study’s lead-in phase – the one Stemline had amended – but that this subsided after three days. A separate obituary for the patient states that she died on January 18.

When contacted by EP Vantage earlier this week Stemline had said it was “not in a position to comment about any specific outcomes that may or may not have occurred in any of our existing trials”.

It was only yesterday that the company acknowledged the death, as well as admitting to having learned of it on January 18. It issued the statement after an article by Adam Feuerstein in The Street prompted Stemline’s stock to crash 43%.

Stemline cautions that the exact cause of the patient’s death is still being investigated; it could be that she died not of CLS but of a secondary complication.

Nevertheless, whatever its precise cause, the death was clearly a material event, having occurred during a fund-raising period. If the $45m secondary’s underwriters were made aware of it, their pressing ahead with the offering suggests that they misjudged its importance.

The secondary was priced at $10 a share, but the stock is currently changing hands at below $6. It is noteworthy that since pricing the offering Stemline has not announced its close; a nightmare scenario could see the secondary fall apart, but this would presumably require the underwriters to prove that they had not been made sufficiently aware of the death.

Target or payload

The issues raise a separate point about the feasibility of targeting CD123; the phase I trial of a separate CD123-targeting project, Johnson & Johnson’s bispecific JNJ-63709178, has for some time been suspended owing to a serious adverse event. Cellectis is seeking permission to start a first-in-human study of its allogeneic CAR-T therapy UCART123.

SL-401’s problems might be due to its cytotoxic payload rather than the antigen it targets. BPDCN is a rare haematological malignancy with no specific treatments and only seven active clinical trials, according to Clinicaltrials.gov; CLS is a known treatment-related toxicity.

Either way further problems loom: two class action suits were launched against Stemline today, and more will surely follow.

Clinical trials of SL-401
Indication Trial ID
BPDCN (pivotal phase II) NCT02113982
Relapsed/refractory AML NCT02113982
AML in first CR patients with MRD+ NCT02270463
Advanced, high-risk myeloproliferative neoplasms NCT02268253
Relapsed/refractory multiple myeloma, Pomalyst combo NCT02661022

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter

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