Gen­Sight has a gene ther­a­py mys­tery on its hands, which is about the last thing it want­ed at the end of Phase III.

As­sess­ing the 48-week da­ta from its first piv­otal test of a treat­ment for Leber Hered­i­tary Op­tic Neu­ropa­thy — or LHON, a rare ge­net­ic dis­ease that caus­es blind­ness — in­ves­ti­ga­tors pulled out a mean­ing­ful im­prove­ment in sight in their one treat­ed eye.  

Bernard Gilly

The mys­tery: The oth­er eyes that re­ceived a sham ther­a­py did just as well with their eye­sight. Ex­act­ly as well.

That makes the Phase III study of GS010 a fail­ure, and rather than stay to try and solve the mys­tery, in­vestors bailed, dri­ving down the Eu­roNext stock $SIGHT down by 34%.

One of the rea­sons why the ear­ly gene ther­a­py pi­o­neers like Gen­Sight picked hered­i­tary eye dis­eases to go af­ter first is that the eye is a con­tained unit, lim­it­ing off-tar­get ef­fects. But Gen­Sight’s Paris-based CEO Bernard Gilly says that as on­ly a frac­tion of pa­tients his­tor­i­cal­ly see a spon­ta­neous im­prove­ment in eye­sight, he’s won­der­ing if the ther­a­py in­ject­ed in­to one eye de­liv­ers an un­ex­pect­ed ben­e­fit to the oth­er.

At the same time, Gen­Sight tout­ed a hit on a reti­nal bio­mark­er for the dis­ease, which they claimed as ev­i­dence that the ther­a­py had an im­pact sep­a­rate from the sham.

“The fact that struc­tur­al mea­sures of the reti­na showed such a large sta­tis­ti­cal dif­fer­ence with treat­ment is com­pelling and ob­jec­tive ev­i­dence that this gene ther­a­py pro­tects the in­tegri­ty of many reti­nal gan­glion cells from the dam­age of LHON,” com­ment­ed com­pa­ny co-founder José-Alain Sa­hel.

That’s a messy ar­gu­ment, with the com­pa­ny ar­gu­ing that it ap­peared the ther­a­py im­proved sight for both eyes, but on­ly hit the sec­ondary bio­mark­er in the treat­ed eye. 

The com­pa­ny — which tried and failed to make it on­to Nas­daq — will be left look­ing for more da­ta to an­a­lyze from its next two Phase III stud­ies, which are up­com­ing. But easy ex­pla­na­tions will be hard to come by.

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.