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.”

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.

#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.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Israel Lowy (Regeneron)

#ES­MO20: 'As good as any PD-1 out there': Re­gen­eron flash­es PD-(L)1 lung can­cer da­ta to ri­val Mer­ck

Regeneron entered the PD-(L)1 game late, so they devised a two-pronged strategy to catch up with Big Pharma rivals: They would push it into cancers where PD-1s had yet been tested, and they would prove that it’s as powerful in the big indications as any other on the market.

They cleared a hurdle on the first goal Friday, showing a 31% response in patients with the rare skin cancer basal cell carcinoma. And with the data they’re rolling out Monday, Regeneron cancer chief Israel Lowy is ready to declare success on the second.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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