Bio­haven touts a pair of PhI­II wins for mi­graine pill, but shares ric­o­chet off of weak da­ta

Bio­haven has re­leased a set of pos­i­tive Phase III da­ta for their fast-act­ing mi­graine drug, which close­ly par­al­lel a ri­val at Al­ler­gan and trail well be­hind Eli Lil­ly’s las­mid­i­tan. And the biotech will now join the scram­ble un­der­way for an ap­proval in a field that’s about to be se­vere­ly dis­rupt­ed.

In­vestors didn’t like the num­bers ear­ly Mon­day morn­ing, send­ing shares $BHVN down 40%. That clear­ly wasn’t the way Bio­haven was bet­ting. The biotech paid Bris­tol-My­ers Squibb $50 mil­lion just a cou­ple of weeks ago to re­struc­ture their li­cens­ing deal, cut­ting the roy­al­ty stream to the sin­gle dig­its. But in the hours up to the close, the stock — backed by some heavy­weight mar­ket play­ers — went on a roller coast­er ride in the red, end­ing the day down 7%.

Al­ler­gan — which will have an­oth­er Phase III tri­al to re­port on — saw its shares rise a bit, while Lil­ly stock jumped close to 2%.

The co-pri­ma­ry end­points for Bio­haven’s oral rimegepant (BHV-3000) was pain free­dom and free­dom from most both­er­some symp­tom 2 hours af­ter tak­ing the pill in two piv­otal stud­ies.

Their pain free­dom rate was 19.2% and 19.6% for the drug, ver­sus 14.2% and 12% for the place­bo arm. Free­dom from MBS was 37.6% and 36.6% ver­sus 25.2% and 27.7% in the sug­ar pill group.

That ev­i­dent­ly may have been sta­tis­ti­cal­ly sig­nif­i­cant, but it wasn’t a big enough spread to con­vince skep­tics won­der­ing about the drug’s clin­i­cal sig­nif­i­cance in a com­pet­i­tive field.

Com­pare rimegepant to Al­ler­gan’s oral CGRP ubro­gepant, where the first Phase III re­port­ed out free­dom for pain at 2 hours for 19.2% and 21.2% for two dif­fer­ent dos­es and 11.8% in the place­bo arm; 38.6% and 37.7% on MBS and 27.8% in the place­bo arm.

Eli Lil­ly’s las­mid­i­tan — which works by hit­ting 5-HT1F re­cep­tors — did even bet­ter, de­spite be­ing dogged by high place­bo rates. Lil­ly $LLY, which paid $960 mil­lion to buy CoLu­cid and las­mid­i­tan, al­so has a CGRP drug that has per­formed in line with the rest of the in­jecta­bles.

Two hours af­ter tak­ing las­mid­i­tan or a place­bo, here were the the lat­est Phase III re­spons­es on free­dom from pain by dosage: 28.6% for 50 mg (p=0.003); 31.4% for 100 mg (p<0.001); 38.8% for 200 mg (p<0.001) and 21.3% for place­bo. In­ves­ti­ga­tors al­so nailed an end­point on free­ing pa­tients of their most both­er­some symp­tom, whether that was nau­sea, sen­si­tiv­i­ty to sound or sen­si­tiv­i­ty to light. The da­ta: 40% for 50 mg (p=0.009); 44.2% for 100 mg (p<0.001); 48.7% for 200 mg (p<0.001) and 33.5% for place­bo.

Back-to-back Phase II­Is, how­ev­er, won’t trans­late in­to a quick FDA fil­ing. Bio­haven not­ed in a re­lease that it won’t be ready to file un­til 2019, keep­ing up with Al­ler­gan on that score.

Vlad Coric

The ri­vals here are bet­ting that they can take mar­ket share for treat­ing mi­graines as heavy­weights com­pete over in­jectable CGRP drugs head­ed to reg­u­la­tors for the pre­ven­tion of acute mi­graine. Am­gen and No­var­tis lead the way on that front, with a drug un­der re­view. Te­va, and Alder are an­gling for a fol­lowup po­si­tion.

The one com­mon char­ac­ter­is­tic of these drugs is that they all per­form in re­mark­ably sim­i­lar ways, leav­ing oral de­liv­ery and price as two fea­tures that these two new ther­a­pies can com­pete on. Al­ler­gan has al­so had to ex­plain some cas­es of liv­er tox in its first Phase III — a con­cern for the class — while Bio­haven says it saw noth­ing to alarm in­ves­ti­ga­tors in its Phase III stud­ies.

Bio­haven CEO Vlad Coric had this to say:

By com­bin­ing pos­i­tive ef­fi­ca­cy re­sults and a fa­vor­able safe­ty pro­file with ease of oral dos­ing, we be­lieve that rimegepant will rep­re­sent a sig­nif­i­cant im­prove­ment over ex­ist­ing treat­ment op­tions.

Bio­haven shares al­so took a beat­ing last fall when their Phase II/III study of tri­grilu­zole demon­strat­ed not on­ly that it didn’t work bet­ter than a place­bo in treat­ing spin­ocere­bel­lar atax­ia, but pa­tients in the study al­so re­port­ed in larg­er num­bers that the place­bo helped them more than the drug.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

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

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,900+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly 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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,900+ biopharma pros reading Endpoints daily — and it's free.

David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,900+ biopharma pros reading Endpoints daily — and it's free.

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:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,900+ biopharma pros reading Endpoints daily — and it's free.