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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.

Embattled CDC director Robert Redfield (AP Images)

Covid-19 roundup: CDC ad­vi­so­ry com­mit­tee de­lays pri­or­i­ty dis­tri­b­u­tion vote; EU re­port­ed­ly in­dem­ni­fy­ing vac­cine mak­ers

A federal committee that advises the CDC was expected to hold a vote Tuesday on a plan regarding the distribution for initial doses of approved Covid-19 vaccines. But that vote has been scrapped.

The Advisory Committee on Immunization Practices, or ACIP, won’t be voting until the committee members learn more about which vaccines become available first, the Wall Street Journal reported. The vote could potentially wait until a specific vaccine is authorized before recommending how to dole out the first doses.

Zai Lab hauls in $761M from Hong Kong IPO to push Ze­ju­la, more bud­ding can­di­dates in Chi­na — re­port

Zai Lab is set to net more than $761 million from its secondary listing in Hong Kong after pricing the IPO at $72.51 (HKD$562) — just a hair below its Nasdaq closing price on Monday, Bloomberg and Nikkei Asian Review reported.

A pioneer in bringing Western drugs to China, co-founder and CEO Samantha Du has more than tripled Zai Lab’s market cap in the three years it’s been public in the US. The HKEX listing is designed to fund R&D and commercialization for the current portfolio while fueling new in-licensing pacts, the biotech wrote in a filing.