Upcoming events – Karyopharm’s partner dream and data for Ultragenyx


Welcome to your weekly digest of approaching regulatory and clinical readouts. Karyopharm’s selinexor will report results in several oncology settings, including multiple myeloma, in the first half of the year (see table below). An earlier link to sepsis has not dampened forecasts, and if safety fears can be quashed this could be the year the company finally bags a partner.

Meanwhile, the first quarter should see phase II data from Ultragenyx’s triheptanoin in glucose transporter type-1 deficiency syndrome, a rare metabolic disorder. The company pulled off an impressive IPO three years ago, and its focus on orphan diseases could start paying off in the next couple of years.


2017 holds a fair few catalysts for Karyopharm, with selinexor results expected from haematological malignancies and solid tumours. The first trial to report will be Sadal in diffuse large B-cell lymphoma, followed by Sopra in AML and Seal in liposarcoma by the middle of the year.

Selinexor is an oral XPO1 inhibitor thought to cause the accumulation of tumour suppressor proteins in cancer cells leading to the induction of apoptosis.

The single-arm Storm trial in multiple myeloma will read out early next year, while a phase III trial called Boston will start soon in multiple myeloma patients who have had one to three prior lines of therapy, possibly moving selinexor into earlier treatment lines.

However, selinexor’s development in AML has been dogged by safety issues, with reports of sepsis in the Sopra trial prompting Karyopharm to lower the studied dose (Karyopharm fails to contain sepsis signal, August 11, 2015). 

According to sellside consensus compiled by EvaluatePharma 2022 sales are expected to reach $1.2bn, with $380m of that through partnering in Europe. The company has cash of $175m, which is expected to fund it until the end of 2018. 

Karyopharm has a second-generation XPO1 inhibitor, KPT-8602, in phase II. The only other similar compound, according to EvaluatePharma, is Stemline Therapeutics’s SL-801, which is in a phase I trial in solid tumours.

Ongoing studies of selinexor
Indication Trial name Details Topline data expected Trial ID
Diffuse large B-cell lymphoma Sadal (Ph IIb) Selinexor (high vs low dose) Early 2017 NCT02227251
Acute myeloid leukaemia Sopra (Ph II) Selinexor vs physician's choice Mid 2017 NCT02088541
Liposarcoma Seal (Ph II/III) Selinexor vs placebo Mid 2017 (Ph II portion) NCT02606461
Multiple myeloma Storm (Ph IIb) Selinexor and dexamethasone Early 2018 (expanded cohort) NCT02336815
Stomp (Ph I/II) Selinexor and dexamethasone + lenalidomide, pomalidomide or bortezomib Primary completion 2018 NCT02343042
Boston (Ph III) Selinexor, bortezomib and dexamethasone vs bortezomib and dexamethasone 2019 Expected to start this year

RARE disease

Transporter type-1 deficiency syndrome, in which Ultragenyx’s triheptanoin is being tested, involves seizures that usually begin in the first few months of life; individuals may also develop symptoms associated with movement disorders such as ataxia and involuntary muscle spasms.

The standard treatment is a strict ketogenic diet, one that is high in fat and low in carbohydrates and causes the body to burn fat for energy instead of glucose. Anti-epileptic drugs are generally ineffective, or afford only limited improvement in the absence of a ketogenic diet.

The phase II double-blind, placebo-controlled study enrolled 40 paediatrics, adolescents and adults who are currently not on, or not compliant with, a ketogenic or other high-fat diet. Patients can maintain standard treatment with one to three anti-epileptic drugs during the study. 

Primary outcome measures include a reduction in the frequency of seizures over six weeks, and safety, with secondary endpoints including change in cognitive function and gross motor function. After the initial double-blind treatment period an open-label extension was completed to 52 weeks, with further outcome measures explored.  

A phase III trial is also recruiting, with data expected in 2018. Triheptanoin is also being testing in Rett syndrome and Huntington’s disease, and carries 2022 consensus forecasts of $316m, according to EvaluatePharma

Ongoing studies of triheptanoin
Study Trial ID
Phase II in transporter type-1 deficiency syndrome NCT01993186
Phase III in transporter type-1 deficiency syndrome NCT02960217
Phase II in Rett syndrome NCT02696044
Phase II in Huntington’s disease NCT02453061

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @ByJoFagg on Twitter

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