What analysts called "upside potential" for PTC Therapeutics Inc.'s ataluren in Europe came to pass with a recommendation for conditional approval of the candidate, to be marketed as Translarna for nonsense mutation Duchenne muscular dystrophy (DMD) in ambulatory patients 5 years and older.

Shares of South Plainfield, N.J.-based PTC (NASDAQ:PTCT) closed Friday at $20.03, up $4.71, or 30.7 percent. The move by the Committee for Medicinal Products (CHMP) for Human Use of the European Medicines Agency puts Translarna in pole position for full approval as the first-ever therapy in the high-ticket rare disease DMD, though there's no guarantee. A decision usually is made about three months after the CHMP advice.

In its written remarks recalling the negative opinion that was given in January, the CHMP noted that the phase IIb study failed to show that patients taking oral Translarna could walk a greater distance on the 6-minute walk test (6MWT) than patients taking placebo, and other measures "provided only limited supportive evidence of the beneficial effects" of the drug.

CEO Stuart Peltz told investors during a conference call that explaining the trial's outcomes by way of a fresh analysis let PTC change the minds of European regulators. "Something I've always stressed during these calls and consultations [is] the need to really help both educate and make them understand" the data's history and meaning, Peltz said, in particular "the consistency of the data in the various stage of the disease process. I think that got them all quite comfortable."

The clean safety profile with Translarna also served PTC well, Peltz said. The CHMP's opinion was "strictly based on the phase IIb trial," he said, with no findings considered from the ongoing phase III experiment. "No real discussion on what the expectations are" from the later-stage study took place, Peltz said.

"I think it's a little bit early now to give you our views on roll-out and things like that," Peltz said, though PTC has been laying the groundwork. "We've always had a strong relationship with lots of the patient advocacy groups," he said, adding that the firm has been "careful about our expenditure on this." Costs likely will rise with the latest news from Europe, but chief financial officer Shane Kovacs said it's "premature to change any guidance in terms of operating expenses."

Caused by a mutation in the dystrophin gene, DMD strikes about one in 3,600 boys (about 20,000 new cases every year), who suffer muscle degeneration that leads to death, usually in the patient's mid-20s. Word about Translarna comes less than a month after a win by DMD player Santhera Pharmaceuticals AG, which hit the primary endpoint in its phase III trial with idebenone, an oral therapy that does not depend on mutational status. (See BioWorld Today, May 14, 2014.)

CF PLAN YET TO 'CRYSTALLIZE'

DMD may be coming of age. Cambridge, Mass.-based Sarepta Therapeutics Inc., with its exon-skipping candidate eteplirsen for the condition, said in April that the FDA had notified the company in a letter that the new drug application (NDA) "should be fileable" with existing data. As with PTC's experience in Europe, the reversal of the earlier view by the U.S. agency boosted Sarepta's stock. Analysts, though, were skeptical about whether the 6MWT with dystrophin biomarker data would really get the job done for Sarepta. (See BioWorld Today, April 22, 2014.)

Sarepta earlier had ended a post-phase II meeting with the agency optimistic about an NDA filing in the first half of this year. Last September, though, Leiden, the Netherlands-based Prosensa Holding NV's exon-skipper drisapersen, partnered with Glaxosmithkline plc, of London, failed in a phase III trial, which most likely skewed the U.S. agency's viewpoint on Sarepta's drug. The primary endpoint in the drisapersen study was a statistically significant improvement on the 6MWT after 48 weeks. (See BioWorld Today, Oct. 14, 2009, April 17, 2013, July 25, 2013, and Sept. 23, 2013.)

Cowen and Co. analyst Edward Nash, in a research report May 8 on PTC's ataluren, noted that the confirmatory phase III trial known as ACT DMD is on track to finish enrollment by the middle of this year, with top-line results in the middle of 2015. "We model full approvals for ataluren in both the U.S. and the EU in 2016 based on positive results from the confirmatory study," Nash wrote, calling the conditional approval in the EU "upside potential." Translarna is the only drug in clinical development for DMD patients with the nonsense mutation, borne by 10 percent to 15 percent of DMD patients, in the dystrophin gene, making the cells quit synthesizing a protein before the process is done.

Ataluren is also in development for cystic fibrosis (CF). Asked whether PTC will file for that indication in Europe, Peltz said company officials still need to "crystallize our thinking on this based on the overall strategy," and will have an answer later. Lancet Respiratory Medicine recently published results of the phase III trial in nonsense-mutation CF, showing positive trends in the primary endpoint, lung function as measured by relative change in percentage of predicted forced expiratory volume in one second and in the secondary outcome measure, rate of pulmonary exacerbations.

In Europe and the U.S., the compound bears orphan drug status. PTC expects that the data from the confirmatory phase III trial, supplemented with the phase IIb results, will support approvals in both.