Santhera Pharmaceuticals AG's latest European holdup in getting the label expanded for Raxone (idebenone) did not dampen the enthusiasm of RBC Capital analyst Matthew Eckler, who allowed that the news "adds a wrinkle to the story" but predicted the nod for Duchenne muscular dystrophy (DMD).

The company said the EMA's Committee for Medicinal Products for Human Use (CHMP) likely will want more information before giving the go-ahead in DMD, though the panel did not ask for more trials. Instead, it wants facts that would bolster the clinical relevance of existing outcomes, and Liestal, Switzerland-based Santhera expects a decision in the third quarter of this year. Originally the answer was believed due late in the first quarter or early in the second quarter. (See BioWorld Today, July 15, 2016.)

The news sent shares of Santhera (ZURICH:SANN) falling 15.7 percent to close Friday at CHF66.50 (US$68.34), down CHF12.35.

Santhera won EU marketing clearance for Raxone in Leber's hereditary optic neuropathy (LHON) in September 2015 and the benzoquinone derivative was launched in October of that year, starting with Germany.

Officials at Santhera could not be reached, but RBC's Eckler said in a report that, "per our discussion with management, the agency has posed a new question related to the risk/benefit profile of Raxone." The nature of the question wasn't specified.

An oral small molecule, Raxone yielded positive data in the 64-patient phase III DELOS trial, and could become the first oral treatment for DMD regardless of mutation status. "While we acknowledge investor concerns over the delayed CHMP recommendation, at this point we continue to expect a positive outcome and label expansion to DMD," he said. Raxone is the only DMD therapy in the works that has tallied a phase III win, and the CHMP has proved its openness to the indication, renewing the marketing application for Translarna (ataluren) for DMD patients with the nonsense mutation, from South Plainfield, N.J.-based PTC Therapeutics Inc., even after the confirmatory trial fizzled. Eckler estimated $257M in 2026 EU sales. (See BioWorld Today, Oct. 18, 2016.)

PTC this year bought Emflaza (deflazacort), the first FDA-blessed corticosteroid for DMD. Government officials questioned "the unusual circumstances" involving the approval just before the sponsor, privately held Marathon Pharmaceuticals LLC, of Northbrook, Ill., agreed to sell it to PTC for $140 million. The up-front amount consisted of about $75 million in cash and the remainder in PTC common shares. Marathon also hung onto the rare pediatric disease priority review voucher that came with Emflaza's approval. Although not previously approved in the U.S., deflazacort was widely available elsewhere in generic form, and DMD patients in the U.S. could find supply via Marathon's expanded-access program or through prescriptions written by U.S. physicians that were filled abroad at importing pharmacies. Days after the drug was approved, commercialization was paused as government scrutinizers balked at the $89,000 annual list price. PTC lowered the amount significantly. (See BioWorld Today, Feb. 13, 2017, Feb. 15, 2017, and March 17, 2017.)

With Santhera's Raxone in the U.S., filing has been delayed until a second phase III trial is done. Last summer, Santhera said the FDA wanted data from the planned SIDEROS trial included in the NDA filing for DMD, and those results aren't expected until mid-2019.

Meanwhile, in LHON, a mitochondrial disease that leads to loss of central vision, "experts we have spoken with believe that there could possibly be significantly more patients than the 500 new annual cases we have modeled," Eckler said, adding that Raxone's mechanism of action on the mitochondria "could potentially lend itself to applications in additional rare disease" that share similar etiology.

Findings in DMD continue to roll out. Recently the Annals of Rehabilitation Medicine published a paper that correlated serum creatine kinase (CK) with pulmonary function. CK has long been considered an important biomarker in DMD, but this is the first time it's been tagged as a worthy forecaster of lung function. "Further studies are needed to clarify whether serum CK has an impact on pulmonary function so that pharmacological and newly developed genetic interventions can be assessed," the paper concluded.

Other players in the space include Boston-based Exonics Therapeutics Inc., using CRISPR/Cas9 gene editing technology with a goal of correcting the mutations that cause DMD and other neuromuscular diseases. DMD Therapeutics Inc., of Seattle, is advancing its small molecule, DMD-813, shown in a preclinical mouse model to reduce muscle damage and inflammation and lead to increased muscle strength and ambulation over long distances. Earlier this year, Cambridge, Mass.-based Solid Biosciences LLC completed the initial close of a $50 million series C financing that it said will help move its experimental gene therapy for DMD in the second half of 2017. RA Capital Management and Bain Capital Life Sciences led the oversubscribed round, which followed a $42.5 million series B that first closed in 2015. The adeno-associated virus-based candidate, called SGT-001, gained U.S. and European orphan status in October last year. (See BioWorld Today, March 1, 2017, and March 31, 2017.)