Novartis’ ‘breakthrough’ muscle drug bimagrumab flunks a late-stage trial

Novartis ($NVS) buried some bad pipeline news in its quarterly report today. The pharma giant says that its “breakthrough” drug bimagrumab (BYM338) failed a Phase IIb/III study for a rare, muscle-wasting disease called sporadic inclusion body myositis--putting a drug that has garnered blockbuster peak sales projections under a cloud.

Novartis kept it short and sour, saying that the drug did not hit the primary endpoint. The company plans to evaluate the full data set before it decides on next steps. But for now, it looks like the latest--and biggest--failure in a string of flops in this niche R&D field.

Novartis jumped on board MorphoSys' antibody discovery platform to find BYM338. The treatment reins in myostatin, and investigators have cited its added potential for cachexia, COPD and sarcopenia. Back in the spring of 2014, MorphoSys execs put its peak sales potential at a whopping $4 billion while the FDA has handed out its breakthrough therapy designation alongside its commitment to speed development efforts.

Novartis’ setback for the lead clinical product in the field could be Scholar Rock’s advantage. The Cambridge, MA-based biotech scored a $36 million B round for its new and perhaps improved myostatin blocker, looking to build muscle in patients suffering from muscle atrophy.

Knocking down myostatin, though, could also be potentially dangerous. Peter Ganz at UCSF has also studied myostatin in preclinical studies, recently determining that lower levels of that protein alongside reduced levels of GDF11 were linked to thickening heart muscles and heart failure.

It's also no simple matter to knock down myostatin in order to build muscle to fight wasting, as Atara--an Amgen ($AMGN) spinoff--found out when its clinical candidate PINTA 745 failed a Phase II study for protein energy wasting in patients with end-stage renal disease, forcing the biotech to halt development efforts and switch focus to cancer. Back in 2011, Acceleron ($XLRN) and Shire ($SHPG) also halted clinical work on ACE-031, another myostatin drug with big dreams in fighting muscle wasting, then decided to scrap it altogether in 2013 after running some additional preclinical tests.

"The outcome of the phase 2b/3 study with bimagrumab in sIBM is disappointing,” said MorphoSys CSO Marlies Sproll in a statement. “Nevertheless, ongoing clinical trials, including those in sarcopenia and hip fracture are continuing as planned at this stage.”

- here's the release