J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an in­creas­ing­ly in­flu­en­tial cost-ef­fec­tive­ness watch­dog in the Unit­ed States, has con­clud­ed in its re­view of treat­ments for car­dio­vas­cu­lar dis­ease that while the cost of J&J’s Xarel­to and Amarin’s Vas­cepa meet its bench­mark for val­ue pric­ing — the two treat­ments will not like­ly treat as many pa­tients as hoped with­out sur­pass­ing the an­nu­al bud­get thresh­old cal­cu­lat­ed by ICER for each ther­a­py.

J&J’s Xarel­to, known chem­i­cal­ly as ri­varox­a­ban, is a blood thin­ner that was orig­i­nal­ly ap­proved to pre­vent deep vein throm­bo­sis in pa­tients un­der­go­ing ma­jor or­tho­pe­dic surgery and is wide­ly used in the man­age­ment of atri­al fib­ril­la­tion and ve­nous throm­boem­bol­ic dis­ease. Last year, it was cleared for use in com­bi­na­tion with as­pirin as a treat­ment to re­duce the risk of ma­jor car­dio­vas­cu­lar (CV) events in pa­tients with chron­ic coro­nary or pe­riph­er­al ar­te­r­i­al dis­ease — on the ba­sis of the piv­otal COM­PASS tri­al that in­di­cat­ed that the com­bi­na­tion spurred a 24% re­duc­tion of the risk of ma­jor CV events in the pa­tient pop­u­la­tion.

Amarin’s Vas­cepa, known chem­i­cal­ly as icos­apent eth­yl, is an omega-3 fat­ty acid de­rived from fish oil that was orig­i­nal­ly en­dorsed by the US reg­u­la­tor as a treat­ment for el­e­vat­ed triglyc­erides. How­ev­er, it is now un­der FDA re­view for an ex­pand­ed la­bel af­ter a land­mark tri­al — RE­DUCE-IT — showed the pill trig­gered a 25% re­duc­tion in the risk for the first oc­cur­rence of a ma­jor car­dio event, and a 26% re­duc­tion for 3-point MACE, a com­pos­ite of car­dio­vas­cu­lar death, non­fa­tal heart at­tack and non­fa­tal stroke. The reg­u­la­tor is set to make its de­ci­sion by De­cem­ber.

At cur­rent prices, both drugs fall with­in the val­ue-based price bench­mark range set by ICER:

Source: ICER, 2019

Click on the im­age to see the full-sized ver­sion

Xarel­to’s an­nu­al list price of $5,457 falls with­in ICER’s val­ue-based price bench­mark range of $5,200-$7,600 per year — in fact, the drug’s es­ti­mat­ed net price of $2,215 per year is sig­nif­i­cant­ly low­er than the ICER bench­mark. Clin­i­cal ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would con­sid­er us­ing the drug in ap­prox­i­mate­ly 30% of el­i­gi­ble pa­tients — but at the cur­rent price — on­ly rough­ly 6% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the po­ten­tial ICER thresh­old of $819 mil­lion an­nu­al­ly. Last year, Xarel­to gen­er­at­ed near­ly $2.5 bil­lion in glob­al sales.

In the case of Vas­cepa, the drug’s an­nu­al list price of $3,699 and es­ti­mat­ed net price of $1,625 are both sig­nif­i­cant­ly low­er than ICER’s val­ue-based price bench­mark range of $6,300-$9,200 per year. Ex­perts at ICER’s pub­lic meet­ing sug­gest­ed they would like to pre­scribe the drug, if ap­proved for the new in­di­ca­tion, to the ma­jor­i­ty of el­i­gi­ble pa­tients — but on­ly about 4% of el­i­gi­ble pa­tients could be treat­ed in a giv­en year with­out cross­ing the ICER thresh­old of $819 mil­lion an­nu­al­ly. In 2018, Vas­cepa gen­er­at­ed rough­ly $229 mil­lion in sales.

ICER’s bud­get thresh­old is based on cal­cu­la­tions that sug­gest that the US health care sys­tem, in the short term, may not be equipped to ab­sorb the ther­a­pies’ ex­pect­ed adop­tion if costs ex­ceed $819 mil­lion per drug, per year — with­out sidelin­ing oth­er drugs/ser­vices or con­tribut­ing to a rapid uptick in in­sur­ance costs.

In terms of long-term ef­fec­tive­ness, ICER found that both ther­a­pies pro­vid­ed gains in over­all sur­vival above and be­yond the cur­rent ar­se­nal of car­dio­vas­cu­lar ther­a­pies. How­ev­er, re­view­ers did high­light some sources of un­cer­tain­ty.

Al­though treat­ment with Xarel­to low­ered the risk of CV events, there was a surge in bleed­ing, re­view­ers not­ed. For Vas­cepa, it is un­clear whether the ther­a­py would be ef­fec­tive in pa­tients not treat­ed with statins — and the min­er­al oil place­bo used in the RE­DUCE-IT tri­al may not have been bi­o­log­i­cal­ly in­ert, they said. In ad­di­tion, al­though the RE­DUCE-IT tri­al test­ed a high­er dose of Vas­cepa, pri­or neg­a­tive re­sults test­ing dif­fer­ent for­mu­la­tions of omega-3 fat­ty acid de­rived from fish oil “have led some to wor­ry that these new re­sults could be wrong by chance.”

“(D)es­pite the re­port’s pos­i­tive con­clu­sion that Vas­cepa is cost-ef­fec­tive, we be­lieve that it un­der­states the true val­ue of Vas­cepa,” Amarin’s chief med­ical of­fi­cer Craig Gra­nowitz said in a state­ment on Thurs­day.

“For ex­am­ple, the re­port’s base-case analy­ses re­flect on­ly the costs of heart at­tack, stroke and car­dio­vas­cu­lar death and ex­clude oth­er high costs as­so­ci­at­ed with oth­er car­dio­vas­cu­lar events demon­strat­ed to be low­ered by Vas­cepa in the RE­DUCE-IT car­dio­vas­cu­lar out­comes study (e.g., revas­cu­lar­iza­tion pro­ce­dures and hos­pi­tal­iza­tion for un­sta­ble angi­na) as well as low­er rates of re­cur­ring car­dio­vas­cu­lar events in pa­tients treat­ed with Vas­cepa dur­ing the study.”

J&J said it had ex­pect­ed ICER to find Xarel­to cost-ef­fec­tive in its new in­di­ca­tion.

“How­ev­er, we do not en­dorse the use of cost-per-QALY or cost-per-life-year-gained analy­sis as the sole or pri­ma­ry ba­sis of de­ci­sion mak­ing,” the com­pa­ny said in a state­ment to End­points News.  

Can­cer may have eclipsed car­dio­vas­cu­lar dis­ease in the de­vel­oped world — al­though CDC es­ti­mates sug­gest it still kills 610,000 in the Unit­ed States every year (that’s 1 in every 4 deaths).

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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Democratic presidential candidate, U.S. Sen. Elizabeth Warren (D-MA) 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.
The Warren plan would rely on the federal government’s compulsory licensing powers to seize the IP of blockbuster drugs like Truvada and Harvoni to provide them at a fraction of what Gilead sells them for in the US. And she would throw some antitrust actions in as needed to rein in the price of Humira, AbbVie’s cash cow that continues to dominate the list of the most profitable therapeutics on the market.
Notably, she plans to rely on the powers already vested in the federal government, rather than suggest remedies that would require the assent of a deeply divided Congress.
In addition to the blockbusters on the list, Warren sends a clear signal that the same tactics would be used to beef up the supply of cheap antibiotics, as needed. And the same action could befall any other therapy patients can’t afford.

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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.