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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

Two and a half years after driving his antisense oligonucleotide platform to Wall Street, Stoke Therapeutics CEO Ed Kaye is painting a fuller picture of the company’s first clinical data. And though the trial wasn’t powered to detect statistical significance, Kaye says the readout shows early signs of efficacy in kids with a rare, drug-resistant form of epilepsy

STK-001 was well-tolerated in single and multiple doses in 22 Dravet syndrome patients between the ages of 2 and 18 years old, Stoke announced on Friday. What’s more, 12 of the 17 evaluable patients at the time (70.6%) saw reductions from baseline in convulsive seizure frequency, according to the company.