The failure of Stem Cell Therapeutics’ NTx-265 in phase II trials for treatment of acute stroke yet another blow to a field that has historically suffered from lack of clinical success leaving very few treatment options for the millions of people worldwide who experience disability due to stroke.
However, a review of EvaluatePharmadata indicates that with desmoteplase, Lundbeck and Paion’s fibrinolytic blood-thinnner, and Pivlaz, Actelion’s endothelin A receptor antagonist, in phase III trials, several new products may soon be filed for stroke, the second-biggest cause of death worldwide (see table below).
But whilst there are quite a number of candidates, the review suggests that the main treatment strategies remain breaking blood clots in the short term and protecting brain tissue in the recovery.
If approved, desmetoplase would take its place alongside marketed clot-busting drug Activase. Pivlaz, meanwhile, targets the subset aneurysmal subarachnoid haemorrhage and seeks to reduce vasospasm. As the only two advanced stroke candidates to which industry observers attach significant sales estimates, this indicates the field is still taking a conservative view of the stroke treatment pipeline. Desmetoplase is expected to complete phase III trials in the third quarter of 2011, with Pivlaz trials ending later this year.
|Selected phase III candidates for stroke|
|Indication||Product||Generic name||Pharma class||Propietary level||Company|
|Stroke, acute||desmoteplase||Plasminogen activator||NME (Patented Compound)||Lundbeck/Paion|
|Subarachnoid hemorrhage||Pivlaz||clazosentan disodium||Endothelin A receptor antagonist||NME (Patented Compound)||Actelion|
|Stroke, acute||Citicoline||citicoline||Vasodilator||NME (Patented Compound)||Teva Pharmaceutical Industries|
|Stroke, acute||DP-b99||-||Chelating agent||NME (Patented Compound)||D-Pharm|
Repairing the damage
What is most disappointing about the failure of NTx-265 is that it would have represented a new stroke treatment in that the human chorionic gonadotropin and epoetin alfa was expected to rebuild brain tissue after a stroke, making it the first disease modifying treatment for the disorder.
However, Its phase IIb trial failed to show any significant difference in the NIH stroke scale results of patients taking the drug and those of patients taking a placebo.
The failure resulted in a 75% plunge in the Canadian company’s share price on May 25. Shares closed on Monday at 10 cents.
In addition to desmetoplase and Pivlaz, which are forecast to respectively have sales of $38m and $303m by 2016 also in phase III is D-Pharm’s DP-b99, a metal-ion trapping agent the Israeli company plans to test in 770 ischemic stroke patients to measure stroke recovery. The trial is expected to finish in 2012.
Leaving aside NTx-265, phase II also has some familiar approaches. Syngis Pharma is trialling filgrastim, known as Neupogen in treatment of neutropenia, in stroke care. Thrombongenics is testing microplasmin, which it is also studying in vitreomacular adhesion. An anti-dementia agent called Translon/Motiva is in phase II for Daiichi Pharmaceutical and Neuren Pharmaceuticals.
A more novel approach is GlaxoSmithKline’s 249320, a humanised monoclonal antibody that blocks inhibition of myelin-associated glycoproteins. The organic Glaxo candidate is being tested in 40 stroke patients to evaluate their recovery, with a study completion date of April 2011.
So whilst there are candidates in stroke, the innovation seems to be lagging and of those in development if past history is anything to go by few will actually make it to market. As such stroke care will continue to look for breakthrough treatments that can save more lives and improve the rehabilitation of patients who suffer the condition.
|Selected phase II candidates for stroke|
|Indication||Product||Generic name||Pharma class||Proprietary level||Company|
|Stroke, acute||AX200||filgrastim||Neuroprotectant||NME (Patented Compound)||SYGNIS Pharma|
|Stroke, acute||V10153||-||Thrombin-activated plasminogen||NME (Patented Compound)||Vernalis|
|Stroke, acute||SA4503||-||Sigma-1 agonist||NME (Patented Compound)||Eisai/M's Science|
|Stroke, acute||Translon (DM-9384)/Motiva||nefiracetam||Anti-dementia agent||NME (Patented Compound)||Daiichi Sankyo/Neuren Pharmaceuticals|
|Stroke, acute||249320||-||Anti-CNS MAb||NME (Patented Compound)||GlaxoSmithKline|
|Stroke, acute||Microplasmin||ocriplasmin||Plasmin||NME (Patented Compound)||ThromboGenics|
|Stroke, acute||NTx-265||human chorionic gonadotropin & epoetin alfa||Stroke agent||NDA + Proprietary Drug Delivery||Stem Cell Therapeutics|
|Stroke, acute||XG-102||-||JNK inhibitor||NME (Patented Compound)||Xigen|
|Stroke, acute||Aspirin-PC||aspirin & phosphatidylcholine||Cyclo-oxygenase (COX) inhibitor||NDA (Patented Compound)||PLx Pharma|