J&J, GSK stum­ble com­ing out of the gate with mixed PhI­II rheuma­toid arthri­tis da­ta for sirukum­ab

This is a big week­end for the wave of late-stage drugs lin­ing up for a slice of the multi­bil­lion-dol­lar rheuma­toid arthri­tis mar­ket. And J&J and Glax­o­SmithK­line got things start­ed by spelling out the da­ta in a less-than-stel­lar matchup against Ab­b­Vie’s Hu­mi­ra.

In­ves­ti­ga­tors turned up at the an­nu­al Amer­i­can Col­lege of Rheuma­tol­ogy meet­ing in Wash­ing­ton DC to re­port a hit and a miss in a Phase III head-to-head be­tween sirukum­ab — a top rheuma­toid arthri­tis drug in both J&J’s as well as GSK’s late-stage pipeline — and Hu­mi­ra.

Pa­tients tak­ing 50 mg of sirukum­ab dosed every 4 weeks and 100 mg dosed every two weeks achieved some­what bet­ter re­spons­es — a 2.58 and 2.96 drop from base­line on the dis­ease ac­tiv­i­ty score —  than the 2.19 drop for pa­tients tak­ing a low­er 40 mg dose of Hu­mi­ra every two weeks. That was a sta­tis­ti­cal­ly sig­nif­i­cant re­sponse.

That Hu­mi­ra reg­i­men, though, beat the 50 mg sirukum­ab dose on hit­ting ACR50, a min­i­mum 50% im­prove­ment in signs and symp­toms of the dis­ease, and bare­ly missed match­ing the 100 mg dose, miss­ing the sec­ond pri­ma­ry end­point in the study. The 50 mg and 100 mg sirukum­ab num­bers hit 27% and 35% on ACR50 com­pared to 32% of the Hu­mi­ra group.

The high dose of sirukum­ab al­so reg­is­tered a high­er rate of se­ri­ous ad­verse events in the 50 mg group, with 7% re­port­ing a se­ri­ous AE com­pared to 3% in the 100 mg group and 4% tak­ing Hu­mi­ra.

In the sec­ond Phase III study among pa­tients re­sis­tant to an­ti-TNF drugs, like Hu­mi­ra, the ACR20 scores were 40% and 45% for the 50 mg and 100 mg sirukum­ab dos­es and 24% in the place­bo arm.

None of that spells dis­as­ter for this drug. But it’s just one of sev­er­al new con­tenders for the mar­ket crown and pay­ers will be de­vot­ing par­tic­u­lar­ly close at­ten­tion to the head-to-head num­bers for Hu­mi­ra, as biosim­i­lars are lin­ing up to dec­i­mate the $14 bil­lion fran­chise — soon­er or lat­er.

J&J has re­peat­ed­ly tapped sirukum­ab as a key part of its Phase III ef­fort to line up ma­jor new prod­ucts for the mar­ket­ing group. GSK, mean­while, has been try­ing to over­come per­sis­tent crit­i­cism that its pipeline lacks piz­zazz. In their deal on sirukum­ab, GSK gained com­mer­cial rights in the US and the West­ern Hemi­sphere, while J&J lined up Eu­rope and the rest of the world.

Still to come this week­end: New da­ta on Eli Lil­ly’s baric­i­tinib, an oral ri­val in-li­censed from In­cyte. Sanofi and Re­gen­eron are grap­pling with a re­cent re­jec­tion for their IL-6 con­tender sar­ilum­ab, stiff-armed by the FDA due to man­u­fac­tur­ing con­cerns, which al­so post­ed a su­pe­ri­or pro­file to Hu­mi­ra for rheuma­toid arthri­tis.

And fur­ther back in the pipeline are even more big drugs that will look to grab best-in-class sta­tus.

A few weeks ago Ab­b­Vie turned its back on Abl­ynx’s Phase III-ready IL-6 drug vo­bar­il­izum­ab, shrug­ging off its $175 mil­lion up­front buy-in, af­ter that drug al­so turned in an unim­pres­sive per­for­mance com­pared to Roche’s Actem­ra. Ab­b­Vie is look­ing to its own in-house pro­gram for ABT-494 to pro­duce the best new drug in the field. Gilead stepped in af­ter Ab­b­Vie al­so spurned its part­ner­ship with Gala­pa­gos on fil­go­tinib, pay­ing $725 mil­lion to ac­quire rights to the JAK1 drug.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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Mer­ck’s $1B cash gam­ble pays off with a sur­pris­ing PhI­II car­dio suc­cess for Bay­er’s heart drug veri­ciguat

More than 3 years after Merck stepped up and paid $1 billion in cold, hard cash to gain the US commercial rights to Bayer’s high-risk heart drug vericiguat in a broad-ranging cardio alliance, the partners say their Phase III study has come through with promising data and a date with regulators.
We don’t have the data, and won’t until they put it out at an upcoming scientific session, but Merck touted the results, saying that their big Phase III VICTORIA study hit the primary endpoint  — with vericiguat combined with available therapies reducing “the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when given in combination with available heart failure therapies.”
Depending on the hard data, and how it breaks out with the combinations used, this drug could pose a threat to Novartis’ blockbuster drug Entresto, currently at $1.6 billion while analysts expect peak sales to hit $4 billion.
The drug is a soluble guanylate cyclase (sGC) stimulator, which Bayer and Merck have had high hopes for. Evidently, so did cardiologists. Cowen’s last analysis set potential sales at $400 million in 2024, but that number could go up significantly now.
Cowen’s Steve Scala noted this morning:
Vericiguat could be a lucrative product for Merck, and one with potentially under-appreciated value. At Cowen’s Therapeutics Conference in September 2019, 80% of specialists anticipated a positive result from VICTORIA whereas only 51% of investors shared this optimism.
Investigators recruited more than 5,000 patients at more than 600 centers in 42 countries for this study — one of the most expensive propositions in R&D. Millions of people in the US suffer from heart failure with reduced ejection fraction when the failing heart fails to contract properly to eject blood into the system. Bayer holds ex-US rights to the drug and also stands to earn cash from the $1.1 billion in milestones Merck agreed on for their collaboration.
Remarkably, the drug was pushed into Phase III despite failing the mid-stage trial — though investigators flagged a success at the high dose of 10 mg. In VICTORIA, researchers started patients at 2.5 mg and then titrated up to 5 and then 10 mg.

Gene ther­a­py wins the in­side track at EMA; PPD files for IPO

→ Gene therapy maker Orchard Therapeutics has been granted an accelerated assessment for OTL-200 by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The gene therapy — in development in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy — being used towards the treatment of metachromatic leukodystrophy.

→ Pharmaceutical Product Development has announced that its parent company, PPD, Inc has submitted a draft to the SEC relating to the proposal of an IPO of the parent company’s common stock. Number of shares and price range have not yet been determined.

Pfiz­er gets biosim­i­lar ap­proved for Hu­mi­ra, set­ting up com­pe­ti­tion — in 2023

In the story lawmakers and drug pricing reform advocates have told about the drug industry, there are perhaps few greater villains than Humira and its maker AbbVie.

Between 2012 and 2018, AbbVie upped the drug’s annual after-rebates cost from $19,000 to $38,000 in the US, with sticker prices now over $60,000 per year — increases that led to accusations of price gouging, most recently from Democratic presidential frontrunner Elizabeth Warren.

Alk­er­mes forges $950M biotech buy­out deal in a bold bet on an ear­ly-stage CNS drug plat­form

Alkermes $ALKS is investing $100 million cash and committing up to $850 million more in milestones in a big wager on a very early-stage CNS discovery platform. And the biotech is adding $20 million more to fund next year’s new research work on the platform it’s acquiring in today’s buyout with an eye to expanding the research work in oncology.

The biotech, helmed by Richard Pops, is buying Rodin Therapeutics, which had focused early on Alzheimer’s disease. Pops’ buyout, though, isn’t focused solely on the most troublesome sector in pharma R&D.

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Eye­ing one of the first RNAi ther­a­pies and cho­les­terol block­buster, Med­Co shows de­tailed in­clisir­an da­ta

The main question was not whether it would work; it was if it would be safe.

The Medicines Company is out with new data on its LDL cholesterol drug inclisiran, and they confirm the first, tentative answers: Yes. They also keep MedCo on track for an imminent  FDA submission for one of the first RNAi therapies and a drug that could flip the cholesterol market. An EU application will follow in the first quarter of 2020.

Image: Associated Press

Af­ter a late-stage miss, No­var­tis touts an­oth­er En­tresto analy­sis to con­vince the FDA to ex­pand the block­buster's la­bel

Fresh after getting its keenly watched sickle cell treatment endorsed by the FDA, Novartis is pulling out all the stops to expand the use of heart therapy Entestro using a raft of analyses after the drug “narrowly” failed a crucial late-stage test.

Entestro is a top seller for Novartis and is currently approved for HFrEF (formerly known as systolic heart failure) — in these patients the heart muscle does not contract effectively, reducing the level of oxygen-rich blood pumped into to the body. The drug is administered twice daily and is designed to cut the strain on the failing heart.

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UP­DAT­ED: Karuna clears PhII hur­dle in schiz­o­phre­nia, takes aim at a piv­otal in block­buster hunt — shares soar

When Karuna went public last year, the biotech cited one small Eli Lilly study of their anti-psychotic xanomeline that delivered a whopping 24-point average improvement in schizophrenics’ PANSS score over placebo — far and above the average 9-10 point advantage cited for the average drug approved for use among these patients.

Now, after wrapping a big Phase II of a xanomeline combo with a sizable 182 patients, the margin on success has shrunk considerably, but the team $KRTX can still count on a solidly positive average outcome as well as — crucially — the safety profile they were looking for.

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