Madri­gal's stock soars on promis­ing PhII da­ta in NASH, but ques­tions linger

The stock is fly­ing for Madri­gal Phar­ma­ceu­ti­cals fol­low­ing news that its fat­ty liv­er dis­ease drug suc­cess­ful­ly pared down liv­er fat in Phase II tri­als. Shares jumped more than 100% Wednes­day morn­ing as the Philadel­phia com­pa­ny preps to com­pete with ti­tans in the space.

Madri­gal $MDGL, which merged with can­cer drug mak­er Syn­ta Phar­ma­ceu­ti­cals last year, is de­vel­op­ing small mol­e­cule drugs in car­dio­vas­cu­lar-meta­bol­ic dis­eases and the hot (and in­creas­ing­ly crowd­ed) field of non-al­co­holic steato­hep­ati­tis (NASH).

Paul Fried­man

This new da­ta is on Madri­gal’s lead com­pound MGL-3196, a once-dai­ly pill for NASH that works as a liv­er-di­rect­ed se­lec­tive thy­roid hor­mone re­cep­tor β-se­lec­tive ag­o­nist.

NASH, a chron­ic liv­er dis­ease caused by fat build-up in the liv­er, af­fects around 15 mil­lion peo­ple in the US. It can lead to fi­bro­sis, or scar­ring, in the liv­er, which can cause liv­er fail­ure and can­cer. The field is a big tar­get for the bio­phar­ma in­dus­try, and com­pa­nies like Madri­gal face ma­jor com­pe­ti­tion from the likes of Gilead, Al­ler­gan, Bris­tol-My­ers Squibb, and oth­ers.

Mad­gr­i­al’s Phase II da­ta is promis­ing, with the drug caus­ing a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in liv­er fat (-36.3%) for pa­tients tak­ing MGL-3196 com­pared to pa­tients on the place­bo (-9.6%).

But some an­a­lysts say fat re­duc­tion in the liv­er won’t nec­es­sar­i­ly set NASH drug mak­ers apart from com­pe­ti­tion. In­stead, the key would be to re­duce scar­ring along­side liv­er fat. Madri­gal said that’s one of its sec­ondary end­points: im­prove­ment in fi­bro­sis by at least one stage with no wors­en­ing steato­hep­ati­tis. The com­pa­ny said mul­ti­ple in­flam­ma­to­ry and fi­bro­sis serum bio­mark­ers at 12 and 36 weeks “are be­ing and will be as­sessed.” Re­sults are ex­pect­ed in Q2 of 2018, the com­pa­ny said in a state­ment.

“We are grat­i­fied to see clin­i­cal re­sults that strong­ly sug­gest MGL-3196 has the po­ten­tial to pro­vide clin­i­cal­ly mean­ing­ful im­prove­ment of NASH by tar­get­ing lipo­tox­i­c­i­ty and in­flam­ma­tion as well as by re­duc­tion of car­dio­vas­cu­lar risk by low­er­ing athero­genic lipids,” said Paul Fried­man, CEO of Madri­gal, in a state­ment. “These pleiotrop­ic ac­tions, cou­pled with the ex­cel­lent safe­ty pro­file we have seen in this tri­al, con­tin­ue to sug­gest that MGL-3196 has the po­ten­tial to ad­dress the root caus­es of the un­der­ly­ing dis­ease process in NASH.”

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls

Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.