Clear­side Bio­med­ical pre­dicts its uveitis drug will be re­ject­ed, af­ter FDA re­quests more da­ta

In its sec­ond-quar­ter up­date ear­li­er this month, eye drug de­vel­op­er Clear­side Bio­med­ical in­di­cat­ed it was look­ing to out-li­cense its lead drug, Xipere, which is cur­rent­ly un­der FDA re­view. But those plans may be put on hold af­ter the com­pa­ny on Thurs­day dis­closed the FDA has asked for more da­ta on the drug’s mar­ket­ing ap­pli­ca­tion.

As a re­sult, Clear­side ex­pects to re­ceive a Com­plete Re­sponse Let­ter from the FDA on or be­fore the de­ci­sion date of Oc­to­ber 19, it said. The drug, Xipere (tri­am­ci­nolone ace­tonide oph­thalmic sus­pen­sion), is be­ing eval­u­at­ed for the treat­ment of mac­u­lar ede­ma as­so­ci­at­ed with uveitis, which is char­ac­ter­ized by in­flam­ma­tion of the mid­dle lay­er of the eye.

Agency of­fi­cials have re­quest­ed Clear­side pro­vide sta­bil­i­ty da­ta on tri­am­ci­nolone ace­tonide (TA) sus­pen­sion pro­duced, em­ploy­ing an ‘en­hanced man­u­fac­tur­ing process’ used by the com­pa­ny. Al­though the for­mu­la­tion of the TA sus­pen­sion has not changed — the agency wants to ver­i­fy the com­pa­ra­bil­i­ty of the sta­bil­i­ty pro­files of the batch­es made with the en­hanced man­u­fac­tur­ing process ver­sus the batch­es orig­i­nal­ly sub­mit­ted as part of the mar­ket­ing ap­pli­ca­tion, Clear­side said.

George Lasezkay “We be­lieve this is pri­mar­i­ly a tim­ing is­sue since our sta­bil­i­ty da­ta from pre­vi­ous­ly man­u­fac­tured batch­es have been con­sis­tent and pre­dictable, and we have every rea­son to be­lieve this will con­tin­ue to be the case…Dis­cus­sions with po­ten­tial XIPERE out-li­cens­ing part­ners re­main on­go­ing,” said Clear­side chief George Lasezkay. “We con­tin­ue to ex­pect that we will have suf­fi­cient re­sources to fund op­er­a­tions in­to the third quar­ter of 2020, with­out re­ly­ing on any part­ner­ship-re­lat­ed pay­ments that we might gain through XIPERE part­ner­ing or R&D col­lab­o­ra­tion agree­ments.”

In­vestors weren’t quite as op­ti­mistic. Shares of the Al­pharet­ta, Geor­gia-based com­pa­ny $CLSD tum­bled more than 38% to 78 cents be­fore the bell on Fri­day.

In a note ear­li­er this month, Need­ham’s Serge Be­langer sug­gest­ed the Xipere was poised to win FDA ap­proval with a broad pan-uveitis la­bel that would dif­fer­en­ti­ate it from oth­er cor­ti­cos­teroids, such as Al­ler­gan’s $AGN Ozur­dex, Bausch Health’s Re­tis­ert and Eye­Point Phar­ma­ceu­ti­cals’ Yu­tiq.

“We pre­vi­ous­ly pegged Xipere’s po­ten­tial peak sales in uveitis at $100MM-$150MM. The out-li­cens­ing of Xipere makes sense from a cor­po­rate strat­e­gy for CLSD since the com­pa­ny’s cur­rent fi­nan­cial re­sources (~$26MM as of 6/30/19) lim­it the abil­i­ty to prop­er­ly in­vest in a prod­uct launch. Xipere’s po­ten­tial is like­ly too small to mer­it its own com­mer­cial in­fra­struc­ture and makes more sense in the hands of a com­pa­ny with an ex­ist­ing sales force,” he wrote.

“We view the change in strat­e­gy as the ide­al sce­nario since it po­ten­tial­ly en­hances the com­mer­cial val­ue of Xipere, which CLSD would have been un­able to achieve with its lim­it­ed fi­nan­cial re­sources (~$26MM as of 6/30/19).”

On Thurs­day, the com­pa­ny sug­gest­ed the FDA’s re­quest had no readthrough to the rest of the com­pa­ny’s plat­form, which is in the pre­clin­i­cal stages and is fo­cused on gene ther­a­py and small mol­e­cules.

So­cial im­age: Shut­ter­stock

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.

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.

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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