A 'high-risk, high-re­ward' ef­fort on NGF pain med fas­inum­ab by Re­gen­eron, Te­va clears a re­vised PhI­II -- se­ri­ous ques­tions linger

Just a few months af­ter Re­gen­eron $REGN and its part­ners at Te­va $TE­VA were forced to drop the two high-dose arms of their Phase III study of the NGF pain med fas­inum­ab, re­searchers say the re­main­ing two low-dose arms cleared a late-stage hur­dle, open­ing the way to more Phase III tri­als as they hunt an elu­sive ap­proval for a brand new class of pain ther­a­pies.

This one isn’t easy.

Just a few months ago the top team at Re­gen­eron un­easi­ly ac­knowl­edged in a Q1 call with an­a­lysts that the in­de­pen­dent mon­i­tor­ing board had told them to shelve the two high­est dos­es in the study, cit­ing con­cerns about the risk/ben­e­fit pro­file. Once a dar­ling in Big Phar­ma cir­cles, NGF drugs were tied to se­vere ad­verse events that forced a lull in tri­al work from 2012 to 2015, un­til re­searchers could per­suade reg­u­la­tors that they could test it with­out threat­en­ing pa­tients. And Re­gen­eron and Te­va have al­ready en­dured a clin­i­cal hold for their pro­gram, which came right af­ter Te­va paid $250 mil­lion to part­ner on the ther­a­py.

George Yan­copou­los

The re­cent set­back on fas­inum­ab stirred some se­ri­ous con­cerns that those old prob­lems had once again be­come an is­sue — while a ri­val late-stage pro­gram at Pfiz­er $PFE and Eli Lil­ly $LLY for tanezum­ab has al­so stirred lin­ger­ing con­cerns. Just a month ago the part­ners said that their drug had al­so cleared a Phase III, but not­ed that the rate of “rapid­ly pro­gres­sive os­teoarthri­tis was ob­served in tanezum­ab-treat­ed pa­tients at a fre­quen­cy of less than 1.5%, and was not ob­served in the place­bo arm.”

“(T)his is a high-risk, high-re­ward pro­gram as we’ve de­scribed in the past,” R&D chief George Yan­copou­los told an­a­lysts in May. “It’s pret­ty well-demon­strat­ed that the mol­e­cule has ac­tiv­i­ty, but it al­so has cer­tain side ef­fects. It’s not os­teonecro­sis, it’s more de­fined as rapid pro­gres­sion of the os­teoarthri­tis in some pa­tients. And this is some­thing that ob­vi­ous­ly has been seen with this class and with our mol­e­cule be­fore. And so what the in­de­pen­dent da­ta mon­i­tor­ing com­mit­tee did was they ob­vi­ous­ly took an analy­sis to look at the ben­e­fit and the risk that is the ther­a­peu­tic ben­e­fit com­pared to their analy­sis of the risk com­ing from these rapid­ly pro­gres­sive os­teoarthri­tis events and they de­cid­ed that we should ter­mi­nate the up­per two dos­es and con­tin­ue with the two low­er dos­es.”

Those two low­er dos­es came through, though. In their re­lease Thurs­day the part­ners not­ed high­ly sig­nif­i­cant p val­ues for the 1 mg dose every 4 and 8 weeks for both pain and phys­i­cal func­tion. They added that the drug al­so hit goals for “key” sec­ondary end­points. Us­ing ra­di­ograph­ic mon­i­tor­ing of their joints, re­searchers pegged the place­bo-ad­just­ed rate of ad­ju­di­cat­ed arthropathies at “ap­prox­i­mate­ly 2%.”

The ma­jor­i­ty of pa­tients suf­fered from os­teoarthri­tis of the knee.

That safe­ty is­sue, says Ever­core ISI an­a­lyst Uber Raf­fat, pret­ty much elim­i­nat­ed any per­ceived val­ue in this drug. And Raf­fat re­mains on high alert re­gard­ing the safe­ty pro­file.

He not­ed Thurs­day morn­ing:

As it stands now, the place­bo-ad­just­ed in­crease in RPOA is 2%  (again, this is the IN­CREASE – we don’t know the ab­solute rates in this tri­al). We did NOT get a clear state­ment in PR for whether there has been a Type 2 RPOA (rapid pro­gres­sive OA type).

If these NGF drugs can get through Phase III in­tact, some an­a­lysts still be­lieve that there’s a big mar­ket wait­ing for a nono­pi­oid pain med. But there’s still a long way to go in Phase III, with this cur­rent read­out cen­tered on a pre­lim­i­nary sub-study. They’re re­cruit­ing pa­tients for three more Phase III stud­ies while this tri­al con­tin­ues on, with a 52-week mark ahead and a fur­ther 72-week safe­ty as­sess­ment.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.