FDA slaps par­tial hold on Macro­Gen­ics for bis­pe­cif­ic can­cer tri­als as liv­er tox spurs safe­ty fears

Leery about signs of liv­er tox­i­c­i­ty among pa­tients tak­ing a B7-H3 × CD3 bis­pe­cif­ic un­der de­vel­op­ment at Macro­Gen­ics $MGNX, the FDA has slapped a par­tial hold on the ear­ly-stage pro­gram.

The par­tial hold — which af­fects their monother­a­py tri­al as well a com­bi­na­tion ef­fort with their own PD-1 check­point MGA012, part­nered with In­cyte — will stop re­searchers from re­cruit­ing new pa­tients, but peo­ple who have al­ready signed up can con­tin­ue treat­ment.

Scott Koenig

Macro­Gen­ics was quick to down­play the move, not­ing that signs of el­e­vat­ed transam­i­nas­es in the sin­gle-drug study were quick­ly re­solved. And the biotech got some quick help from an­a­lysts, who haven’t been pay­ing all that much at­ten­tion to this pro­gram’s par­tic­u­lar po­ten­tial. CD3, though, plays a promi­nent role in some lead­ing bis­pe­cif­ic ef­forts, and the an­a­lysts would like to know more if the prob­lem here may ex­tend to oth­er de­vel­op­ers.

Macro­Gen­ics has been test­ing this bis­pe­cif­ic in pa­tients with non-small cell lung, blad­der and head and neck can­cer, mesothe­lioma, melanoma, and oth­er B7-H3 pos­i­tive tu­mors.

Jonathan Chang

Leerink’s Jonathan Chang passed along man­age­ment’s con­fi­dence that it can get past this hitch in short or­der and has al­ready pitched a new plan to boost sup­port­ive care in the tri­als.

Over­all, man­age­ment seemed bull­ish that the par­tial clin­i­cal hold could be lift­ed as ear­ly as Jan­u­ary 2019 based on the reg­u­la­to­ry dis­cus­sions so far and the changes be­ing pro­posed, in our view. Man­age­ment in­di­cat­ed that liv­er func­tion test (LFT) el­e­va­tions were ini­tial­ly ob­served in the Q2 week­ly dos­ing reg­i­men, which re­solved with a re­duc­tion in dose. How­ev­er, LFT el­e­va­tions were then ob­served in a cou­ple more pa­tients at a low­er dose.

Umer Raf­fat at Ever­core ISI is in the group that wants to learn more AS­AP.

We sus­pect the liv­er tox in the B7-H3 x CD3 DART may be ON-tar­get tox of this spe­cif­ic com­bi­na­tion. Al­though the com­pa­ny says B7-H3 ex­pres­sion is high in sol­id tu­mors and min­i­mal in nor­mal tis­sues, oth­er sources (see an im­age from the Hu­man Pro­tein At­las at bot­tom) sug­gest B7-H3 (aka CD276) has medi­um to high ex­pres­sion in var­i­ous tis­sues, in­clud­ing the liv­er… If nor­mal cells al­so ex­press B7-H3, then this DART may in­duce more im­mune ac­ti­va­tion than ex­pect­ed, in non-tu­mor en­vi­ron­ments like the liv­er. This is just a hy­poth­e­sis, and we need to see fur­ther clin­i­cal da­ta on safe­ty – it’s hard to make a de­fin­i­tive call giv­en the lim­it­ed de­tail we’ve seen thus far.

“As we’ve iden­ti­fied to the FDA, we be­lieve that transamini­tis ob­served in pa­tients ad­min­is­tered MGD009 was like­ly a cy­tokine-me­di­at­ed event,” not­ed CEO Scott Koenig in a state­ment. “We are work­ing with the FDA and will pro­vide an up­date when we have ad­di­tion­al in­for­ma­tion. This par­tial clin­i­cal hold does not im­pact on­go­ing clin­i­cal stud­ies for enobli­tuzum­ab and MGC018, our oth­er B7-H3-tar­get­ed mol­e­cules.”

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.

The key dates for KRAS watch­ers through the end of the year — the trail is nar­row and risks are ex­treme

There’s nothing quite like a big patent win when it comes to burnishing your prospects in the pipeline. And for Amgen, which seems to have rescued Enbrel for a run to 2029, the cheering section on Wall Street is now fixed on AMG 510 and a key rival.

And it didn’t take much data to do it. 

There was the first snapshot of a handful of patients, with a 50% response rate. Then came word that Amgen researchers are also tracking responses in different cancers, at least one in colorectal cancer and appendiceal too. 

Bain's Or­ly Mis­han joins Pfiz­er's neu­ro spin­out Cerev­el; On­colyt­ic virus biotech taps Sil­la­Jen ex­ec He­le­na Chaye as CEO

→ Bain Capital is deploying one of its top investors to Cerevel Therapeutics, steering a $350 million-plus neuro play carved out of Pfizer. Orly Mishan — a co-founder and principal of Bain’s life sciences unit — was involved in the partnership that birthed the biotech spinout in the first place. As Cerevel’s first chief business officer, she is tasked with corporate development, program management as well as technical operations. 

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.