Near­ly two months af­ter get­ting the boot from the NIH’s AC­TIV-3 study over a failed fu­til­i­ty analy­sis, No­var­tis and Mol­e­c­u­lar Part­ners are back with mid-stage re­sults they say prove their Covid-19 an­tivi­ral works bet­ter in pa­tients who aren’t hos­pi­tal­ized — and CEO Vas Narasimhan likes what he sees.

The phar­ma gi­ant is putting down more than $162 mil­lion to in-li­cense enso­vibep from Mol­e­c­u­lar Part­ners af­ter the can­di­date met its pri­ma­ry end­point of vi­ral load re­duc­tion over eight days in the first part of a Phase II/III study, the part­ners an­nounced on Mon­day.

Mol­e­c­u­lar Part­ners’ stock $MOLN got a rough­ly 20% boost on the news, pric­ing in at $19.92 on Mon­day morn­ing.

Michael Stumpp

How­ev­er, the part­ners have yet to re­veal any hard da­ta on the pri­ma­ry end­point. In fact, the on­ly da­ta point they did re­port on was a 78% re­duc­tion in the risk of Covid-re­lat­ed hos­pi­tal­iza­tion, ER vis­its and death com­pared to place­bo (a sec­ondary end­point), which Mol­e­c­u­lar COO and co-founder Michael Stumpp said was sta­tis­ti­cal­ly sig­nif­i­cant. If you take ER vis­its out of that equa­tion, the an­tivi­ral re­port­ed an 87% re­duced risk in hos­pi­tal­iza­tion and death com­pared to place­bo, CEO Patrick Am­stutz said.

A to­tal of 407 non-hos­pi­tal­ized adults with Covid-19 were en­rolled in Part A of the Phase II/III EM­PA­THY study, which test­ed three dif­fer­ent dos­es of enso­vibep (75mg, 225mg and 600mg). In the place­bo arm with 99 pa­tients, there were six events (event rate of 6.0%); five pa­tients were hos­pi­tal­ized, two of whom died due to wors­en­ing of Covid-19, and one pa­tient had an ER vis­it on­ly. But on­ly four of 301 pa­tients across the enso­vibep arms (1.3%) saw such events, and no pa­tients in the enso­vibep arm died, ac­cord­ing to No­var­tis.

Re­searchers al­so re­port­ed a ben­e­fit in time to sus­tained clin­i­cal re­cov­ery, an­oth­er sec­ondary end­point, which Stumpp said was sta­tis­ti­cal­ly sig­nif­i­cant. More da­ta will be pre­sent­ed at a sci­en­tif­ic con­gress lat­er this year, a No­var­tis spokesper­son told End­points News.

Enso­vibep main­tained “po­tent in vit­ro pan-vari­ant ac­tiv­i­ty against all vari­ants of con­cern iden­ti­fied so far, in­clud­ing Omi­cron,” No­var­tis said in a state­ment.

The phar­ma has cho­sen to pro­ceed with the low­est dose, 75 mg, and aims to en­roll an­oth­er 1,700 pa­tients in Part B, the Phase III por­tion of the study. But even with­out the Phase III da­ta, Narasimhan is al­ready talk­ing about plans to file for an EUA.

“We are now re­view­ing the topline re­sults from EM­PA­THY Part A to de­ter­mine next steps for the de­vel­op­ment pro­gram and a strat­e­gy for reg­u­la­to­ry sub­mis­sions to ob­tain fast-track ap­provals. Fol­low­ing re­view of the re­sults, we plan to ini­ti­ate EM­PA­THY Part B as quick­ly as pos­si­ble, with the low­est ef­fec­tive dose iden­ti­fied in Part A of 75mg,” a spokesper­son said.

No­var­tis was not avail­able for an in­ter­view as of press time.

Patrick Am­stutz

The com­pa­ny bought in­to the enso­vibep pro­gram back in Oc­to­ber 2020, putting down $22 mil­lion up­front and an­oth­er $44 mil­lion for a chunk of eq­ui­ty. In May, the com­pa­ny launched a Phase II/III tri­al, spon­sored by Mol­e­c­u­lar Part­ners, to test the can­di­date in ear­ly-stage Covid pa­tients. Now, No­var­tis is ex­er­cis­ing its op­tion to snap up the rights, which will cost it rough­ly an­oth­er $162 mil­lion plus “sig­nif­i­cant roy­al­ties” on sales.

“These en­cour­ag­ing re­sults come at a time when the need for ther­a­pies with pan-vari­ant ac­tiv­i­ty, such as enso­vibep, has nev­er been greater,” Am­stutz said in a state­ment.

It hasn’t been smooth sail­ing for enso­vibep, which was kicked out of the NIH’s AC­TIV-3 study back in No­vem­ber af­ter fail­ing a fu­til­i­ty analy­sis in hos­pi­tal­ized Covid-19 pa­tients.

The mol­e­cule comes from a class of drugs de­vel­oped by Mol­e­c­u­lar Part­ners that aims to per­form the same func­tions as an­ti­bod­ies with far more tar­get speci­fici­ty and an­tivi­ral pro­tec­tion. Though the DARPin can­di­date ap­peared safe, it failed to show ef­fi­ca­cy at day 5, when a to­tal of 470 pa­tients were as­sessed on their need for sup­ple­men­tal oxy­gen, me­chan­i­cal ven­ti­la­tion or oth­er sup­port­ive care.

“It could very well be, that’s the op­ti­mistic part, that in sub­groups there is some­thing. But at the same time, it’s such a dif­fi­cult and het­ero­ge­neous set­ting, that maybe the fu­til­i­ty was the right point to say, ‘Let’s re­think, let’s look at the da­ta,” Stumpp said.

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

German mRNA player BioNTech opened the doors to a new manufacturing facility on Thursday, this one just about 75 miles north of its headquarters in Mainz, Germany.

BioNTech announced on Thursday that it has completed the construction of its first plasmid DNA manufacturing facility in Marburg, Germany. The facility will produce materials for mRNA-based vaccines and therapies along with cell therapies.