Billed as po­ten­tial block­buster, No­var­tis' sick­le cell drug scores FDA's break­through ther­a­py sta­tus

Vas Narasimhan

Tout­ed by No­var­tis chief Vas Narasimhan as a po­ten­tial block­buster, the Swiss drug­mak­er’s sick­le cell dis­ease (SCD) drug has se­cured the FDA’s break­through ther­a­py des­ig­na­tion for its abil­i­ty to pre­vent de­bil­i­tat­ing­ly painful va­so-oc­clu­sive cri­sis for pa­tients af­fect­ed by the group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try.

SCD pa­tients have atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape. Symp­toms such as ane­mia, re­peat­ed in­fec­tions and pe­ri­od­ic episodes of pain called va­so-oc­clu­sive crises (VOC) when sick­le shaped red blood cells get stuck in­side blood ves­sels be­gin to ap­pear in ear­ly child­hood. These episodes de­prive the body of oxy­gen-rich blood, which can cul­mi­nate in wide­spread tis­sue and or­gan dam­age — par­tic­u­lar­ly in the lungs, kid­neys, spleen, heart and brain — and dras­ti­cal­ly di­min­ish life ex­pectan­cy.

The drug, called crizan­l­izum­ab or SEG101, came to No­var­tis in 2016 via an ac­qui­si­tion of Se­lexys Phar­ma­ceu­ti­cals in a deal val­ued at up to $665 mil­lion. Da­ta showed the drug re­duced the me­di­an an­nu­al rate of VOCs lead­ing to health care vis­its, and an analy­sis of Phase II da­ta pre­sent­ed at the ASH con­fer­ence last year al­so showed that 35.8% of those giv­en the ex­per­i­men­tal treat­ment did not ex­pe­ri­ence a VOC, ver­sus 16.9% on the place­bo arm in pa­tients with a his­to­ry of 2-10 VOCs in the pre­ced­ing year. Af­ter ini­tial­ly sug­gest­ing a mar­ket­ing ap­pli­ca­tion would be sub­mit­ted in 2018, No­var­tis said it would make its case for the drug in 2019.

Ex­ist­ing SCD ther­a­pies are dai­ly oral med­ica­tions, but com­pli­ance is low at about 50%, Cowen an­a­lysts wrote in a note in 2018 fol­low­ing No­var­tis’ R&D day in No­vem­ber.

“Con­verse­ly, crizan­l­izum­ab is a once per month IV in­fu­sion, re­sult­ing in ad­van­ta­geous dos­ing but with the ob­vi­ous ad­min­is­tra­tion hur­dle. No­var­tis be­lieves that the month­ly ad­min­is­tra­tion could fa­cil­i­tate com­pli­ance through reg­u­lar health­care vis­its,” the an­a­lysts not­ed, adding that they had fore­cast sales of $200 mil­lion in 2024 for the drug.

No­var­tis, which es­ti­mates there are about 100,000 SCD pa­tients in the Unit­ed States with rough­ly 60% ex­pe­ri­enc­ing 2 or more VOCs an­nu­al­ly, on Tues­day re­it­er­at­ed it was plan­ning a reg­u­la­to­ry sub­mis­sion in the first half of 2019.

Last month, in yet an­oth­er sign of the FDA’s en­hanced flex­i­bil­i­ty un­der com­mis­sion­er Scott Got­tlieb, Glob­al Blood Ther­a­peu­tics $GBT man­aged to con­vince reg­u­la­tors to al­low its ex­per­i­men­tal drug, vox­elo­tor, to be eval­u­at­ed un­der the ac­cel­er­at­ed ap­proval path­way for sick­le cell dis­ease on the ba­sis of ear­ly da­ta from an on­go­ing late-stage study.

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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Vas Narasimhan. Getty Images

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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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: 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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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.

FDA re­buffs lit­tle As­ser­tio Ther­a­peu­tic­s' long-act­ing ACTH for­mu­la­tion, shares sink

Tiny Assertio Therapeutics’ shares plunged pre-market on Tuesday, after the FDA has spurned its man-made version of the hormone ACTH, which was being reviewed as a diagnostic for patients presumed to have adrenocortical insufficiency.

The Lake Forest, Illinois-based drugmaker said its development partner West Therapeutic Development had received a complete response letter from the US regulator, which indicated that that certain “pharmacodynamic parameters were not adequately achieved” for the product.

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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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.