Ex-Ab­b­Vie part­ner Prin­cip­ia posts en­cour­ag­ing PhII re­sults for its BTK-in­hibitor

Months af­ter their breakup with high-pro­file part­ner Ab­b­Vie, Prin­cip­ia an­nounced pos­i­tive pre­lim­i­nary re­sults from the sec­ond half of a Phase II tri­al on their lead drug.

The San Fran­cis­co biotech an­nounced da­ta from part B of its Phase II open-la­bel tri­al test­ing the BTK in­hibitor PRN1008 on pa­tients with pem­phi­gus vul­garis, a rare au­toim­mune dis­ease af­fect­ing the skin and mu­cous mem­branes. Of 15 en­rolled pa­tients, 6 achieved com­plete re­spons­es and 4 re­main on the ther­a­py.

Nine of the pa­tients achieved a PDAI score – a 0-to-250 met­ric for the sever­i­ty of blis­ter­ing dis­eases – of one or ze­ro.

Mar­tin Babler

Part B mea­sured the drug over a 24-week pe­ri­od rather than Part A’s 12-week pe­ri­od, and found im­prove­ment: The per­cent­age of pa­tients with a com­plete re­cov­ery went from 25% to 40%.

Baird’s Bri­an Sko­r­ney wrote that the re­sults bod­ed well for Prin­cip­ia as it con­tin­ues with a Phase III study on the same com­pound that be­gan last year and is still un­der­way. That tri­al will dose pa­tients for 37 weeks. It aims at 120 en­rollees and will be com­plet­ed at the end of 2021.

“We be­lieve that these re­sults fur­ther sup­port the util­i­ty of BTK in­hi­bi­tion in pem­phi­gus and should fur­ther de­risk this pro­gram as Prin­cip­ia looks ahead to top-line da­ta from the Phase 3 PE­GA­SUS which are ex­pect­ed in 1H22,” Sko­r­ney wrote, adding that the longer dos­ing pe­ri­od in Phase III may yield more com­plete re­mis­sions.

PRN1008 re­ceived FDA or­phan drug sta­tus for pem­phi­gus vul­garis in 2017. The dis­ease, which caus­es blis­ter­ing and ul­cers and is spurred by au­toan­ti­bod­ies break­ing the bond be­tween skin cells, af­fects 40,000 Amer­i­cans and 170,000 peo­ple world­wide.

As re­cent­ly as March, Ab­b­Vie was work­ing on ear­ly-stage re­search with Prin­cip­ia un­der a 2017 deal that gave Prin­cip­ia $15 mil­lion up­front and $667.5 mil­lion in po­ten­tial mile­stones. Prin­cip­ia abrupt­ly an­nounced in March that Ab­b­Vie had de­cid­ed to end the col­lab­o­ra­tion.

“Ab­b­Vie has com­plet­ed an ini­tial eval­u­a­tion of Prin­cip­ia’s high­ly se­lec­tive, oral­ly bioavail­able co­va­lent in­hibitors of the im­muno­pro­tea­some and, af­ter an as­sess­ment of their bi­o­log­ic pro­files rel­a­tive to Ab­b­Vie’s de­sired dis­ease ar­eas of fo­cus, has de­ter­mined that there is no longer a strate­gic fit,” Prin­cip­ia CEO Mar­tin Babler said at the time.

That news came nine days af­ter Prin­cip­ia pub­licly an­nounced pos­i­tive re­sults from their Phase II, part A study.

The au­toim­mune spe­cial­ist went pub­lic last year for an up­sized $106 mil­lion on the strength of its line of BTK in­hibitors. The Ab­b­Vie de­par­ture leaves it with a main ma­jor col­lab­o­ra­tor in Sanofi. In 2017, the French gi­ant li­censed PRN2246, their BTK in­hibitor for mul­ti­ple scle­ro­sis, for $40 mil­lion up­front and $765 mil­lion in po­ten­tial mile­stones.

BTK (Bru­ton’s ty­ro­sine ki­nase) in­hibitors have long been a ma­jor play­er in hema­tol­ogy but in re­cent years they have al­so be­come a tar­get for au­toim­mune re­searchers – a nat­ur­al leap giv­en they act on an en­zyme in B cells, a crit­i­cal part of the body’s im­mune sys­tem.

Re­sults, though, have been mixed thus far. Mer­ck KGaA an­nounced last month they were mov­ing their BTK, evo­bru­ti­nib, in­to Phase III for mul­ti­ple scle­ro­sis de­spite mixed Phase IIb re­sults. Last year, Eli Lil­ly wrote off a BTK for rheuma­toid arthri­tis it had li­censed from Ko­rea’s Han­mi, lead­ing to the col­lapse of a $690 mil­lion pact. Cel­gene sim­i­lar­ly saw its au­to-im­mune BTK fiz­zle in Phase II, while Bris­tol-My­ers Squibb has giv­en few up­dates on its ear­ly-stage BTK pro­gram.

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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Elizabeth Warren speaks during the Nevada Democrats' "First in the West" event at Bellagio Resort & Casino on November 17, 2019 in Las Vegas, Nevada (Getty Images)

Eliz­a­beth War­ren pro­pos­es us­ing com­pul­so­ry li­cens­ing, an­titrust ac­tions to break bio­phar­ma’s con­trol of drug pric­ing — and here are the block­busters she’s tar­get­ing first

Nancy Pelosi’s drug pricing bill may have sparked some industrial strength headaches on the money side of biopharma, but Elizabeth Warren seems determined to become biopharma’s Nightmare on Pennsylvania Avenue.

Warren, one of the top-ranked candidates for the Democratic presidential nomination backing Medicare for all, is circulating a new plan that promises to break the industry’s grip on drug prices — and she has some very specific examples of how she would do it.

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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.

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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(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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Left to right: Arthur Pappas, Robert Nelsen, Peter Kolchinsky Doug Cole and David Beier

In rare po­lit­i­cal for­ay, top biotech in­vestors urge Con­gress to re­ject drug pric­ing bill

Thirteen of the top biotech venture capitalists in the country wrote a letter last week warning lawmakers that if Congress passes a drug pricing bill House Speaker Nancy Pelosi has put before lawmakers, they won’t be able to invest in biomedical research at their current rate, and patients will suffer.

“If policies such as those included within H.R. 3, the Lower Drug Costs Now Act, are passed, our ability to continue to invest in future biomedical innovation will be severely constrained, thus crushing the hopes of millions of patient waiting for the next breakthroughs to treat or cure their cancers, rare genetic diseases, Alzheimer’s, or other serious and life-threatening conditions,” they wrote in a letter addressed to the highest-ranking Democrats and Republicans in the House and Senate and acquired by Endpoints News. 

Dicer­na scores broad, 'rest of liv­er' deal with No­vo Nordisk, bag­ging $225M in cash to hit some 30 tar­gets with RNAi plat­form

Turns out Dicerna wasn’t done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker — which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH — is also purchasing $50 million worth of Dicerna’s equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

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.