Es­pe­ri­on’s cho­les­terol drug clears the last big safe­ty hur­dle, turn­ing the cor­ner to the FDA — now the big chal­lenge looms

Es­pe­ri­on $ES­PR looks set to make the fi­nal step in its long jour­ney to­ward a mar­ket­ing ap­pli­ca­tion at the FDA, with good odds of suc­cess next year. But the lat­est batch of pos­i­tive safe­ty and ef­fi­ca­cy da­ta won’t dis­pel the per­sis­tent ques­tions over its sales strat­e­gy.

Tim Mayleben

That’s go­ing to take some hard dol­lar num­bers.

First, the tri­al da­ta.

The drug arm saw a mod­er­ate drop in LDL of 18% with a 19% cut in high-sen­si­tiv­i­ty C-re­ac­tive pro­tein. That fits in well with what we’ve seen be­fore in a string of Es­pe­ri­on stud­ies, with the ther­a­py fit­ting neat­ly be­tween the gener­ics that dom­i­nate the mar­ket and the PC­SK9s that have had trou­ble find­ing trac­tion, spurring some deep dis­count­ing that could spell trou­ble for Es­pe­ri­on.

It was safe­ty where Es­pe­ri­on faced the steep­est chal­lenge, as ear­li­er ques­tions fo­cused on some con­tro­ver­sial mor­tal­i­ty is­sues that at least tem­porar­i­ly desta­bi­lized the stock. An­a­lysts want­ed these 52-week re­sults to get a much bet­ter idea of any risks pre­sent­ed by this drug. But as Jef­feries’ Michael Yee not­ed, Es­pe­ri­on’s be­mpe­doic acid came through with a clean bill of health.

In the pri­ma­ry safe­ty analy­sis for this study, the two con­cerns ap­pear al­le­vi­at­ed here with no ma­jor is­sues: (1) CV deaths were bal­anced at 0.8% drug vs 0.8% pbo, (2) there were no fa­tal AEs due to neo­plasms/ can­cer. Oth­er SAEs and fa­tal AEs were gen­er­al­ly bal­anced (e.g. SAEs of 20% vs 19% pbo and fa­tal AEs of 1.1% vs 0.8% pbo), and none of the fa­tal AEs were de­ter­mined to be re­lat­ed to study med­ica­tion. The fa­tal AEs would be bal­anced at 0.8% vs 0.8% pbo as well, ex­cept for two one-off cas­es ob­vi­ous­ly not even re­lat­ed to drug – so we be­lieve the fa­tal AEs are bal­anced.

The com­pa­ny is al­so mak­ing much out of a trend to­ward a ben­e­fit on ma­jor car­dio events, or MACE, but they’ll have to nail down that one with an out­comes study, which will take years to play out, with a read­out planned for 2022.

Es­pe­ri­on’s ex­ec­u­tive team plans to sub­mit their US ap­pli­ca­tion in ear­ly 2019, with an EMA pitch com­ing soon af­ter.

That all sound­ed good to in­vestors, who pushed up Es­pe­ri­on’s share price by 10% in pre-mar­ket trad­ing Mon­day.

As­sum­ing there are no nasty sur­pris­es to come in the reg­u­la­to­ry process, what can we ex­pect in a mar­ket­ing show­down be­tween lit­tle Es­pe­ri­on and the gi­ants at Re­gen­eron/Sanofi and Am­gen which have been slash­ing their prices on the PC­SK9 — break­throughs that have demon­strat­ed a mod­er­ate but sig­nif­i­cant ben­e­fit in car­dio risk re­duc­tion?

The three big play­ers have been steadi­ly ax­ing away at their orig­i­nal prices af­ter pay­ers es­sen­tial­ly blocked ac­cess to their drugs to a ma­jor pop­u­la­tion. Es­pe­ri­on CEO Tim Mayleben — who is aim­ing at a sig­nif­i­cant por­tion of the mar­ket that doesn’t get what they need from statins and don’t need what they can get from PC­SK9s — has told me re­peat­ed­ly that they still ex­pect to price in un­der the PC­SK9 over­lords, but his abil­i­ty to main­tain a price ad­van­tage will be at the dis­cre­tion of the big 3.

Amarin’s re­cent out­comes da­ta, which wowed every­one on its (sep­a­rate) in­dus­tri­al-strength fish oil ap­proach with triglyc­erides, al­so un­der­scores just how change­able the mar­ket has been.

You can al­so count Ethan Weiss, a car­di­ol­o­gist at UC San Fran­cis­co, as one of the skep­ti­cal ob­servers. In a Tweet out af­ter the da­ta ar­rived, he not­ed:

I see the most like­ly case as be­mpe­doic acid as be­ing a more $$ eze­tim­ibe. Less like­ly: un­ex­pect­ed ben­e­fit due to in­flam­ma­tion or oth­er ef­fects. Al­so pos­si­ble it has no CVOT ben­e­fit or stud­ies not pow­ered ad­e­quate­ly

The big take­away, though, is that Es­pe­ri­on ap­pears poised to chal­lenge the ma­jors, set­ting up a fur­ther dis­rup­tion that pay­ers should be more than hap­py to see. 

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — and they're prep­ping a pitch to the FDA

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company says that a new analysis of an old dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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Photo credit: Jacquelyn Martin

Where are the in­ter­change­able biosim­i­lars?

In June 2017, Leah Christl, former biosimilar lead at FDA, told a conference in Chicago that interchangeable biosimilars were likely coming to the US market within two years.

And although no interchangeable biosimilar has been approved by FDA yet, and Christl has since moved on to Amgen, progress on interchangeable biosimilars has been slow in the intervening years.

Most recently, Boehringer Ingelheim announced that it has completed, as of last April, a switching study necessary for launching an interchangeable biosimilar for Humira (adalimumab), although the company did not offer any further details on the timing of its submission to FDA or whether there will be an advisory committee to review the data. Boehringer already has an adalimumab biosimilar approved by FDA, which it will launch in the US on 1 July 2023.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.