
Santhera -- A Duchenne Drug With Positive Study Results That Few Know About
NEW YORK (TheStreet) -- Santhera Pharmaceuticals (SANN.SW) doesn't get much attention from investors, which is surprising for two reasons.
The company is developing a drug to treat Duchenne muscular dystrophy, a rare, inherited muscle-wasting disease very much on Wall Street's radar screen. Santhera has also accomplished something that higher-profile DMD companies BioMarin (BMRN) - Get Report, PTC Therapeutics (PTCT) - Get Report and Sarepta Therapeutics (SRPT) - Get Report have not done to date: complete a successful phase III study.
On Friday, results from the positive phase III study involving Santhera's DMD drug idebenone will be presented during a plenary session at the American Academy of Neurology annual meeting. The presentation follows the publication of the same idebenone study in The Lancet earlier this week.
Santhera is scheduled to meet with the U.S. Food and Drug Administration sometime in the next few weeks, after which it expects to submit idebenone for approval by the middle of the year. That puts the company on the same regulatory timeline as Sarepta and a bit behind BioMarin. Santhera is also working toward a European approval filing in DMD this year.
Idebenone is a pill designed to stimulate mitochondria, the energy-producing organelle found inside cells. Santhera is developing idebenone to improve the lung function of DMD patients. The progressive weakening of muscles in the chest of DMD patients leads to respiratory disease and breathing problems.
Santhera's focus with idebenone is symptomatic improvement for DMD patients. The drug isn't intended to be disease modifying like the "exon skippers" drisapersen and eteplirsen being developed by BioMarin and Sarepta, respectively. But drisapersen and eteplirsen are suitable only in patients with a specific genetic mutation, where idebenone has the potential to benefit all DMD patients and could be used in combination with disease-modifying drugs, if approved.
In the phase III study, 64 DMD patients, 90% of them unable to walk and in wheelchairs, were randomized equally to 52 weeks of treatment with idebenone (300 mg three times daily) or a matching placebo. The primary endpoint of the study was the comparative change in lung function, measured by the peak expiratory flow as percentage predicted (PEF%p).
Patients treated with idebenone reported a PEF%p decline of 2.57% after one year compared with an 8.84% decline in placebo patients, according to the Lancet publication. The statistically significant difference of 6.27 percentage points at one year demonstrates idebenone slowed the loss of lung function compared to placebo. Idebenone's lung function benefit, as measured by PEF, was also statistically significant over placebo at 26 and 39 weeks.
The positive effect of idebenone in DMD patients was supported by other measures of lung function, delays in the onset of lung infections and relative improvement in cough strength. Transient but mild diarrhea was more common in idebenone-treated patients than the placebo group. Other common side effects reported were cold symptoms and headache.
"Efficacy data from this trial show that idebenone significantly reduced the loss of respiratory function in patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids," the trial authors conclude in the Lancet paper. "With its favourable safety and tolerability profiles, idebenone therefore is a suitable treatment option to ameliorate a life-threatening complication of Duchenne muscular dystrophy."
Commenting on the Santhera phase III study in a Tuesday blog post, John Porter, CEO of Parent Project Muscular Dystrophy, said, "This is an important and certainly not a modest effect on respiratory function and may well have a substantial effort on quality of life for Duchenne ... We very much look forward to the approval of [idebenone] and to the potential use of the drug in a combination therapy approach to Duchenne."
Approval of idebenone in the U.S. is not without risk. Santhera's use of peak expiratory flow as the primary measure of lung function improvement in the phase III study could raise some concern at the FDA because regulators are more comfortable evaluating drugs based on forced vital capacity, a different measure of lung function.
Santhera included improvement in forced vital capacity (FVC) as a secondary endpoint in the study, but the difference between idebenone and placebo was not statistically significant at one year. There was a statistically significant FVC benefit favoring idebenone over placebo when measured at 13, 26 and 39 weeks.
If idebenone is approved in the U.S. and Europe for DMD, peak sales could exceed $500 million using conservative pricing, forecasts RBC Capital analyst Simos Simeonidis. He also believes Santhera is likely to put itself up for sale if idebenone is approved.
One commercial issue which Santhera will need to navigate around is CoenzymeQ, a chemically similar, gray-market version of idebenone available as a nutritional supplement. Some DMD patients are known to take CoenzymeQ today.
Santhera insists its prescription-grade idebenone is chemically unique and superior to CoenzymeQ. The company points to prior FDA statements that idebenone is an investigational medicine and therefore cannot be marketed as a nutritional supplement.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.









