A new av­enue for di­et pill mak­ers? UC San Diego re­searchers un­cov­er root of lep­tin re­sis­tance

Let’s be hon­est, the mar­ket for weight loss drugs has most­ly been bust. While the in­dus­try has moved on from the fen-phen fi­as­co of decades past, new­er di­et pills like Belviq and Qsymia have still failed to de­liv­er big sales. In the back­ground, how­ev­er, sci­en­tists con­tin­ue to un­pack the com­pli­cat­ed in­ter­nal mech­a­nisms that lead to obe­si­ty. And a team of re­searchers in San Diego say they’ve dis­cov­ered some­thing that might give drug­mak­ers re­newed hope.

The news comes from a col­lec­tion of re­searchers at the Uni­ver­si­ty of Cal­i­for­nia San Diego (UCSD) who just pub­lished their find­ings in Sci­ence Trans­la­tion­al Med­i­cine. In short, they say they’ve un­cov­ered a mol­e­c­u­lar mech­a­nism that caus­es lep­tin re­sis­tance, a well-known phe­nom­e­non con­nect­ed to obe­si­ty. In mice stud­ies, they found a high-fat di­et pro­duced an en­zyme named MMP-2. This en­zyme goes around “clip­ping” the hor­mone re­cep­tors for lep­tin on the sur­face of neu­ronal cells. If the re­cep­tor is clipped, then lep­tin nev­er binds to neu­ronal cells in the hy­po­thal­a­mus — mean­ing your brain nev­er gets the sig­nal that your bel­ly is full and you should stop eat­ing.

Cred­it: Uni­ver­si­ty of Cal­i­for­nia San Diego

Click on the im­age to see the full-sized ver­sion


“We opened a new field of study for meta­bol­ic dis­ease,” said Rafi Ma­zor, a re­search sci­en­tist at the UCSD and the pa­per’s first au­thor. “We need to ask what oth­er path­ways, in ad­di­tion to lep­tin and its re­cep­tors, un­der­go a sim­i­lar de­struc­tive process and what the con­se­quences might be.”

Rafi Ma­zor

Ma­zor is part of a team that in­cludes oth­er UCSD re­searchers, the Salk In­sti­tute for Bi­o­log­i­cal Stud­ies in La Jol­la, Tel Aviv Uni­ver­si­ty in Is­rael, and Monash Uni­ver­si­ty in Aus­tralia.

The team is call­ing for a large-scale clin­i­cal tri­al to see if MMP-2 in­hibitors might help peo­ple lose weight.

The study was led by Ma­zor and UCSD pro­fes­sor Geert Schmid-Schon­bein, which you can see in full here.

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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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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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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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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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: Watch out Bay­er, Roche is com­ing for you with a dis­count price ri­val to the tu­mor ag­nos­tic drug you got from Loxo

Just ahead of schedule the FDA has come through with a key approval for Genentech’s tumor agnostic entrectinib — now headed to the market as Rozlytrek.

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