FDA tells Sprout Phar­ma, like it or not the black box on Ad­dyi stays, but we will di­lute the warn­ing

When the con­tro­ver­sial first drug for low sex­u­al de­sire in women was fi­nal­ly grant­ed ap­proval in 2015, crit­ics ac­cused the FDA of bow­ing to pres­sure from ad­vo­cates by sanc­tion­ing the use of a drug that was found to be mar­gin­al­ly ef­fec­tive in clin­i­cal tri­als, and dan­ger­ous when tak­en with al­co­hol. On Thurs­day, the agency re­buked the mak­er of the drug, Ad­dyi, by re­fus­ing to en­ter­tain the com­pa­ny’s quest to dis­card the black box warn­ing car­ried by the treat­ment, but agreed to damp­en the strong warn­ing on the ba­sis of post­mar­ket­ing da­ta.

Ad­dyi, known chem­i­cal­ly as flibanserin, is de­signed for pre­menopausal women whose lack of sex­u­al de­sire caus­es dis­tress. Pa­tients who took Ad­dyi in a clin­i­cal tri­al had an in­crease of about one sex­u­al­ly sat­is­fy­ing event per month, ver­sus those giv­en a place­bo.

The pink pill — nick­named the “fe­male Vi­a­gra” — has lit­tle in com­mon with the Pfiz­er $PFE block­buster, which was ap­proved decades ago as the pi­o­neer­ing erec­tile dys­func­tion treat­ment. While Vi­a­gra im­pacts blood flow and is tak­en as-need­ed, Ad­dyi was de­signed to ac­ti­vate sex­u­al im­puls­es in the brain and must be tak­en every day.

In par­tic­u­lar, Ad­dyi’s la­bel car­ries a black box warn­ing, high­light­ing the risk of po­ten­tial­ly dan­ger­ous low blood pres­sure and faint­ing, no­tably when tak­en with al­co­hol.

On Thurs­day, the reg­u­la­tor made clear that Ad­dyi’s la­bel must be mod­i­fied to clar­i­fy there is still a con­cern about con­sum­ing al­co­hol close in time to tak­ing Ad­dyi, but that it does not have to be avoid­ed com­plete­ly. Af­ter an­a­lyz­ing da­ta from post­mar­ket­ing stud­ies, the FDA said the warn­ing in­side the black box should re­flect that women should dis­con­tin­ue drink­ing al­co­hol at least two hours be­fore tak­ing Ad­dyi at bed­time or to skip the dose that evening and that women should not con­sume al­co­hol at least un­til the morn­ing af­ter tak­ing Ad­dyi at bed­time.

The reg­u­la­tor has prover­bial­ly put its foot down and is com­pelling Ad­dyi mak­er Sprout Phar­ma­ceu­ti­cals to make the change af­ter the two par­ties were un­able to reach an agree­ment. “We work dili­gent­ly with com­pa­nies to make la­bel­ing up­dates but oc­ca­sion­al­ly are un­able to reach an agree­ment. In those rare cas­es…we have im­por­tant au­thor­i­ties to com­pel com­pa­nies to make safe­ty la­bel­ing changes that are crit­i­cal for the safe use of an ap­proved prod­uct,” the agency said in a state­ment.

Cindy Eck­ert and Robert White­head

Click on the im­age to see the full-sized ver­sion

The founders of Sprout Phar­ma­ceu­ti­cals have long had a strained re­la­tion­ship with the FDA. Chief Cindy White­head (now Cindy Eck­ert) co-found­ed the com­pa­ny with her then-hus­band Robert White­head in 2011, af­ter sell­ing an­oth­er drug com­pa­ny they had spawned to­geth­er af­ter it was is­sued mul­ti­ple FDA warn­ings re­lat­ed to its mar­ket­ing tac­tics.

Sprout pur­chased flibanserin from Ger­many’s Boehringer In­gel­heim, which orig­i­nal­ly de­vel­oped it and took it to the FDA, on­ly to be de­nied ap­proval in 2010. Un­der Sprout, the drug was eval­u­at­ed in ad­di­tion­al stud­ies, but the FDA re­ject­ed it again in 2013. In­censed by the re­jec­tion, Sprout — with the sup­port of some women’s groups —  ag­gres­sive­ly lob­bied the FDA to get the drug across the fin­ish line, by ac­cus­ing the US agency of gen­der bias (a charge the reg­u­la­tor de­nied).

The FDA fi­nal­ly ap­proved the treat­ment — with a boxed warn­ing — on Au­gust 19, 2015, the very next day Sprout an­nounced it was be­ing sold to Valeant (now Bausch Health) for a tidy $1 bil­lion. The hon­ey­moon didn’t last long — in 2017, an em­bat­tled Valeant re­turned Sprout to its orig­i­nal own­ers.

Last month, Sprout is­sued a cheer­ful press re­lease, sug­gest­ing post­mar­ket­ing da­ta in­di­cat­ed that treat­ment with Ad­dyi did not re­sult in faint­ing or hy­poten­sion that re­quired med­ical at­ten­tion. But the FDA took is­sue with that as­sess­ment, say­ing the safe­ty pre­cau­tions built in­to the tri­al did not al­low for an ad­e­quate as­sess­ment of this risk. “For ex­am­ple, women with low blood pres­sure while ly­ing down…were not per­mit­ted to stand up to have blood pres­sure mea­sure­ments tak­en or had to have re­peat­ed blood pres­sure mea­sure­ments while ly­ing down un­til they were high enough for the women to safe­ly stand up. As a re­sult, the da­ta col­lect­ed had miss­ing or de­layed blood pres­sure mea­sure­ments from these women while stand­ing.”

The reg­u­la­tor was al­so not sat­is­fied with how the post­mar­ket­ing tri­als were con­duct­ed, point­ing out that in one tri­al, there were “miss­ing or de­layed mea­sure­ments for blood pres­sure from when the women were first lay­ing down to when they stood up that are crit­i­cal in de­ter­min­ing the risk of hy­poten­sion and syn­cope when tak­ing Ad­dyi and al­co­hol to­geth­er.” The agency al­so flagged that many more women had miss­ing or de­layed blood pres­sure mea­sure­ments when they took Ad­dyi and al­co­hol to­geth­er, com­pared to when they con­sumed al­co­hol or Ad­dyi alone.

Al­to­geth­er, the “pat­tern of the miss­ing or de­layed mea­sure­ments” pro­vides fur­ther ev­i­dence of an in­ter­ac­tion be­tween Ad­dyi and al­co­hol that can en­hance the risk of hy­poten­sion and faint­ing, the agency un­der­scored.

Sprout must com­ply with the FDA’s la­bel­ing de­ci­sion or risk mon­e­tary fines and/or en­force­ment in the form of prod­uct seizure and in­junc­tion. The com­pa­ny has un­til April 16 to ap­peal.

End­points News has con­tact­ed Sprout for com­ment.


Im­age source: Allen G. Breed AP

Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

UCB tries to win some re­spect in the crowd­ed pso­ri­a­sis mar­ket with a dual IL-17 ap­proach — and it won't be easy

For a pharma company with about $5 billion in revenue, a couple of respectably sized blockbuster drugs on the market and some high-profile partners like Amgen, Belgium’s UCB has kept an unusually low profile on the pipeline side of things over the years.
Until now.
Just days after striking a $2.1 billion deal to buy Ra Pharmaceuticals and its C5 rival to Soliris, UCB is posting positive top-line Phase III results for a dual IL-17 inhibitor that it’s steering into one of the most competitive commercial spaces in the industry. And despite plenty of obvious challenges as they struggle to roll out Evenity with Amgen and patent expirations loom on its franchise drugs, including Cimzia, the company just may be ready to tackle some of the biggest players on the planet.
In their first of 3 Phase III studies for bimekizumab, researchers touted top-line wins on statistically significant results on clearing plaque psoriasis, including a victory over J&J’s IL-23 contender Stelara on key endpoints. The drug targets both IL-17A and IL-17F, a modification on the IL-17A strategy laid out for Taltz (Eli Lilly) and Cosentyx (Novartis). And the new group also includes J&J’s Tremfya and AbbVie’s Skyrizi.
We don’t know the PASI90 and IGA scores — but UCB knows that with the kind of heavyweight competition it faces with Novartis and others, marginal gains for patients won’t stack up. So we’ll be watching for the hard numbers. And there’s another head-to-head with Cosentyx that will play a big role in pushing up analysts’ projections on peak sales, which currently fall well short of blockbuster status.
UCB hasn’t exactly been in the spotlight for the last few years, but it’s in a position now that the company has to win some respect in R&D, with blockbuster projects that can keep investors’ attention at a time the industry is experiencing booming R&D development efforts around the planet.
It hasn’t been easy. There was a setback on a lupus drug partnered with Biogen. But there have been some advances, with a deal to buy Proximagen’s NDA-ready nasal spray therapy USL261, designed as a rescue therapy for acute repetitive seizures, for $150 million in cash and another $220 million in sales and regulatory milestones. There was even a report that the company was kicking the deflated tires at Acorda, though nothing came of that.
Late last year UCB also committed to spend up to £200 million on a new R&D hub in the UK.
That may not translate into a lot of excitement right now, but they’re trying. And there’s a subtle promise that more deals may be in the works.

Swamy Vijayan. Plexium

San Diego up­start de­buts dis­cov­ery en­gine that puts a twist to pro­tein degra­da­tion

For years, the idea of protein degradation — utilizing the cell’s natural garbage disposal system to mark problematic proteins for destruction — remained an elegant but technically difficult concept. But now established as a promising clinical strategy, with major biopharma players such as Bayer, Gilead and Vertex trying to grab a foothold via partnership deals, a San Diego startup is looking to exploit it and push its limits.

CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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