Santhera Pharmaceuticals suffered a critical blow to its research programme for Catena in Friedriech’s ataxia as a second phase III trial showed the oral formulation of coenzyme Q-10 missed its primary and secondary endpoints. Now the question for the Swiss company is how it manages finances and the rest of its pipeline as it awaits clinical validation of its other products in the neuromuscular and cancer space.
Santhera’s shares plummeted by nearly 40% in early afternoon trading today to a record low of SFr15 on news of the trial failure. Company executives said the variable progression of the disease and daily fluctuations make it difficult to demonstrate improvements in neurological functions, but stressed that the firm has sufficient cash to continue to fund trials of Catena, known generically as idebenone, in four other indications as well as three other pipeline candidates.
Trends, not significance
In its readout of the 232-patient, one-year Miconos trial in Europe, Santhera said patients taking up to 2,250mg a day of Catena did not show significant improvements from baseline in their mean score on the International Cooperative Ataxia Rating Scale (ICARS) when compared to patients in the placebo arm. The study also failed on secondary endpoints that involved the proportion of patients that improved on the ICARS score and changes in the Friedreich’s ataxia rating scale.
A further meta-analysis of 344 patients in phase II and III studies showed trends toward improvement, but no significant improvements, the company said.
Friedreich’s ataxia is undoubtedly a condition of dire clinical need without any pharmacological treatment (Therapeutic focus - Friedreich's ataxia a goal with few shots, May 20, 2010). An inherited condition that inhibits production of the protein frataxin, which is vital for proper function of cellular mitochondria, Freidreich’s ataxia affects about 1 in 50,000 people in the US. Typical management of the condition involves mobility assistance and insertion of a metal rod in the spine to halt scoliosis.
It is for this reason that Health Canada authorised the marketing of Catena under a notice of compliance with conditions, which the agency uses for investigational drugs with an acceptable risk/benefit profile and the promise of clinical effectiveness. Canadian officials have yet to state whether they will review or look to withdraw Catena's license.
Analysts from Piper Jaffray note that Catena recorded SFr1.6m ($1.39m) in sales in its first full year in Canada, and that only privately insured patients can obtain the drug under conditional approval.
Coming as it did almost exactly a year after Catena failed on the same primary endpoint in the 70-patient Ionia trial in the US, the latest announcement must surely throw cold water on the drug's effectiveness in this indication (Santhera falls on Catena trial failure, May 19, 2009). Without a product on the market, save for conditional approval of Catena in Friedreich’s ataxia in Canada, the company has pressing needs in its pipeline.
Not the least of these is testing Catana in indications such as Duchenne muscular dystrophy, Leber’s hereditary optic neuropathy, and a form of dementia called mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The drug is in phase III for Duchenne muscular dystrophy and phase II for the remainder
It has partnered the Parkinson’s disease agent fipamezole with Biovail, has in-licensed the muscular dystrophy drug omigapil from Novartis, is working alone on its MC4 receptor antagonists on cancer wasting and has partnered an MEK inhibitor with Merck KGaA for a number of cancer indications (Biovail transformation continues with Santhera deal, August 24, 2009).
As the company shed 26 of its 82-employee workforce in July last year, it has managed to extend its cash runway into 2012. It ended 2009 with SFr53.3m in cash. However, with the loss of a lead indication, Santhera could clearly use a win.