FDA ap­proves drug for rare con­di­tion that trig­gers in­tense pain from light ex­po­sure

Five years af­ter EU reg­u­la­tors ap­proved a ther­a­py to treat a rare in­her­it­ed meta­bol­ic con­di­tion that caus­es ex­treme sen­si­tiv­i­ty to light, the FDA has en­dorsed the treat­ment — mark­ing the first-ever ap­proval for pa­tients with ery­thro­poi­et­ic pro­to­por­phyr­ia (EPP) in the Unit­ed States.

The ther­a­py, which is ad­min­is­tered via an im­plant in­sert­ed sub­cu­ta­neous­ly, was de­vel­oped by Aus­tralian drug mak­er Clin­u­v­el Phar­ma­ceu­ti­cals and is sold as Sce­nesse.

In pa­tients with EPP, the ac­tiv­i­ty of fer­rochelatase — an en­zyme in­volved in the pro­duc­tion of a key com­po­nent in he­mo­glo­bin — is com­pro­mised. Re­duced fer­rochelatase ac­tiv­i­ty caus­es the ac­cu­mu­la­tion of pro­to­por­phyrin IX (PPIX) — and light ex­po­sure on the skin can re­act with PPIX, spark­ing in­tense pain, red­ness and thick­en­ing.

Sce­nesse, known chem­i­cal­ly as afame­lan­otide, binds with the melanocortin-1 re­cep­tor on the sur­face of melanocyte cells found in the epi­der­mis of the skin. This trig­gers a cas­cade of re­ac­tions that re­sult in the melanocyte fa­vor­ing the pro­duc­tion of eu­me­lanin (black/brown) over pheome­lanin (red/yel­low). The pro­duc­tion of eu­me­lanin in the skin in­de­pen­dent of ex­po­sure to sun­light or ar­ti­fi­cial light sources of­fers the pa­tient the abil­i­ty to cope with the mol­e­c­u­lar dam­age caused by light.

In Jan­u­ary, STAT pro­filed a Con­necti­cut woman who com­pared the pain she felt from light ex­po­sure to the ex­pe­ri­ence of hav­ing boil­ing oil poured on her hands and knees. On­ly around 600 Amer­i­cans suf­fer from EPP. Switzer­land and Italy had Clin­u­v­el agree to pay 80% of the drug’s cost be­fore al­low­ing it, ac­cord­ing to STAT.

“We are de­ter­min­ing our pric­ing strat­e­gy (in the Unit­ed States) but our ap­proach is go­ing to be far more trans­par­ent and fair than many of our peers. For this we re­fer you to our ap­proach to pric­ing in Eu­rope,” a Clin­u­v­el spokesper­son told End­points News.

Sce­nesse is priced in Eu­rope at €14,101 per in­jectable im­plant, or €56,404 per pa­tient based on four in­jectable im­plants per an­num (ex­clud­ing lo­cal tax­es), the spokesper­son added.

The US ap­proval for Sce­nesse was based on twin place­bo-con­trolled clin­i­cal tri­als. In the first 93-pa­tient tri­al, 48 sub­jects were giv­en Sce­nesse, while the rest were on place­bo.  Af­ter 180 days of ex­po­sure to di­rect sun­light be­tween 10 am and 6 pm, pa­tients on the ther­a­py were pain-free for a me­di­an 64 hours, ver­sus 41 hours for those in the place­bo arm.

In the oth­er 74-pa­tient study, 38 re­ceived Sce­nesse, while the rest got place­bo. Pa­tients were fol­lowed for 270 days which they spent out­doors be­tween 10 am and 3 pm and were as­sessed for pain lev­els — al­though the analy­sis did not in­clude sun ex­po­sure on days pa­tients re­port­ed spend­ing time in a com­bi­na­tion of both di­rect sun­light and shade. The me­di­an to­tal num­ber of hours un­der these con­di­tions in which pa­tients felt ‘no pain’ was six hours for pa­tients re­ceiv­ing Sce­nesse and 0.75 hours for pa­tients re­ceiv­ing place­bo.

Clin­u­v­el formed in 1987 af­ter re­searchers start­ed work­ing on the idea of syn­the­siz­ing hu­man hor­mones to pro­tect the skin.

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 63,000+ 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 63,000+ biopharma pros reading Endpoints daily — and it's free.

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 63,000+ 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 63,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ 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.