Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase III data on Mast Therapeutics’ vepoloxamer will soon show whether the company can succeed in an area – sickle cell disease – in which Bluebird Bio and Global Blood Therapeutics crashed in December.
Newron Pharmaceuticals, meanwhile, must hope that its long road to the US market will come to an end with an FDA approval for Xadago by the close of the month. European Union endorsement bodes well for the add-on to levodopa in Parkinson’s disease, which was knocked back by American counterparts in 2014.
Vepoloxamer is intended to treat vaso-occlusive crisis, an extremely painful consequence of sickle cell disease, rather than the underlying condition. Crisis occurs when sickled red blood cells stick to each other and to the lining of blood vessels, especially in the microvasculature. The only treatment is symptomatic: opioids for the pain.
Epic, the largest-ever placebo-controlled clinical trial in sickle cell disease, aims to show that vepo can become the first project to treat the crisis directly. Vepo binds to the damaged parts of a blood cell’s membrane, preventing them sticking together and allowing the cell to heal.
The study is assessing vepo’s ability to reduce the duration of vaso-occlusive crisis, compared with placebo, following IV administration. Study participants are to be followed for the duration of their hospital stay, expected to average around four days, and for 30 days afterwards. Enrolment of Epic’s 388 patients concluded last month so topline results should be available early next quarter.
Vepo’s originator, CytRx, conducted a phase III study in sickle cell disease which reported in 2001. CytRx concluded the study at 255 patients after running out of money – it was initially to have enrolled 350. Unsurprisingly this flawed study did not achieve statistical significance on its primary endpoint of crisis duration.
15 years later, having licensed the asset from CytRx, Mast believes it can do better. One aspect in its favour is that around 60% of the Epic patients are taking hydroxyurea. In the first phase III trial the proportion of patients with crisis resolution at 168 hours was around 200% better if patients were on hydroxyurea, compared with a 50% improvement if they were not, according to analysts from Roth Capital Partners.
Mast needs the Epic trial of vepoloxamer trial to succeed. The company’s stock tanked last month after an $8m equity raise priced 35% below where the stock was trading.
If it succeeds after all, Mast could find itself with the bestselling sickle cell drug, reaching $189m in 2020, according to EvaluatePharma consensus forecasts. This compares with just $17m for Bluebird Bio’s LentiGlobin BB305 and $16m for Pfizer’s rivipansel.
Xadago, or safinamide, aims to improve the amount of time daily that Parkinson’s disease patients are able to move without difficulty, also known as “on time”. Its pivotal Motion and Settle trials respectively showed a significant improvement in the unified Parkinson’s disease rating scale in patients using a single dopamine agonist, and improved on time.
Levodopa can control motor symptoms of Parkinson’s, but as the disease progresses its effectiveness declines and patients can experience more off time. Add-ons like Xadago have sought to extend the amount of time patients with fluctuating motor control on levodopa alone retain control.
European regulators approved the agent in February 2015, and it has since been launched in four countries by Newron's global marketing partner Zambon – most recently in Italy, where both companies are headquartered. Zambon acquired the Scandinavian group Niigard last year to extend its marketing punch to northern Europe.
Xadago’s progress in the US has been less straightforward, however. It received a refuse to file letter in July 2014 because of formatting issues, including the failure of its draft package insert to conform to FDA guidelines.
The resubmission was accepted a year ago. The FDA extended the original December 29, 2015, PDUFA deadline to March 29 after a late-cycle review meeting in which Newron submitted financial disclosure forms from the two pivotal trials.
Approval will probably trigger some business development activity as Zambon and Newron seek to penetrate the much larger US market. Big pharma groups active in Parkinson’s disease include AbbVie, GlaxoSmithKline, Novartis and Roche, with smaller companies like Boehringer Ingelheim, UCB, Mylan and Lundbeck also potential partners.