FDA snubs Sanofi, Lex­i­con on their pitch for SGLT1/2 di­a­betes drug so­tagliflozin, com­pa­nies mum on what went wrong

Sanofi’s shot at a last-place show­ing for its SGLT1/SGLT2 di­a­betes drug has end­ed in a painful prat­fall ahead of the fin­ish line. The phar­ma gi­ant and their part­ners at Lex­i­con $LXRX say that so­tagliflozin, a ma­jor play­er for their di­a­betes port­fo­lio, has been re­ject­ed by the FDA.

Lon­nel Coats, Lex­i­con

Their terse re­lease gave no ex­pla­na­tion for what went wrong, but an ex­pert pan­el pro­vid­ed a split vote on the mon­ey ques­tion re­gard­ing safe­ty and ef­fi­ca­cy, with in­sid­ers at the agency field­ing big con­cerns about ev­i­dence of di­a­bet­ic ke­toaci­do­sis.

In the US, the FDA is re­quired to stay silent on these CRLs, leav­ing it up to the com­pa­nies to say any­thing they like, or noth­ing at all. Lex­i­con is stay­ing be­hind the stone wall of­fered by the agency.

Lex­i­con ex­ecs set up a quick call on Fri­day af­ter­noon, but giv­en re­peat­ed chances to char­ac­ter­ize the is­sues the FDA has — and the $60 mil­lion ques­tion on whether reg­u­la­tors are de­mand­ing more da­ta or posed chal­lenges that can be dealt with in the near-term — CEO Lon­nel Coats re­peat­ed­ly bat­ted back the queries with­out an­swer­ing them.

That does not bode well for the com­pa­ny or any prospects it may have in the US mar­ket, as com­pa­nies are rou­tine­ly anx­ious to seize on short cuts to CRLs. Lex­i­con al­so has hun­dreds of mil­lions of dol­lars in mile­stone mon­ey sit­ting on the ta­ble for late-stage reg­u­la­to­ry goals and com­mer­cial launch­es.

In­vestors didn’t like the sound of si­lence, slam­ming Lex­i­con shares, which dropped 24%.

Eli Lil­ly’s Jar­diance, which had an im­pres­sive fol­lowup on its car­dio pro­file, along with J&J’s In­vokana and As­traZeneca’s Farx­i­ga are on­ly SGLT2 tar­get­ed. Steglatro from Mer­ck and Pfiz­er ar­rived in late 2017, leav­ing Sanofi and Lex­i­con try­ing to play catchup with a spe­cial 1/2 on of­fer for Type 1 di­a­betes, adding an oral drug to in­sulin for bet­ter glycemic con­trol.

Every month in added de­lays gives the com­pe­ti­tion that much ex­tra time to ex­pand their leads, and chal­lenge Sanofi and Lex­i­con on var­i­ous unique as­pects of their pitch. In the mean­time, the part­ners ex­pect a Q2 ap­proval in Eu­rope, where reg­u­la­tors have proven far more open to the mar­ket­ing ap­pli­ca­tion.

While Lex­i­con will be pun­ished more se­vere­ly, the set­back won’t play well for Sanofi, ei­ther. The com­pa­ny has been try­ing to take charge of its own des­tiny by push­ing for­ward new and im­por­tant drugs. But it’s been ham­pered by a se­ries of sna­fus, in­clud­ing the go­ing on­bat­tle that it’s now fight­ing with of­fi­cials in the Philip­pines over its dengue vac­cine.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Bank­rupt an­tibi­otics mak­er Ar­a­digm turns to old part­ner/in­vestor for fi­nal $3M fire sale

Grifols once paid Aradigm $26 million for a stake in its inhaled antibiotics. But with Aradigm now in bankruptcy, the Spanish drugmaker is dishing out a final $3.2 million to buy it all.

The fire sale — which comes one year after Aradigm filed for Chapter 11 following a regulatory trifecta for disaster — will see Grifols obtain assets and IP to Apulmiq (formerly Pulmaquin and Linhaliq in Europe), Lipoquin and free ciprofloxacin. In addition to waiving its claims in the bankruptcy case, Grifols also agreed to milestone payments up to $3 million more upon any regulatory approvals.

DB­V's peanut pre­ven­tion patch ap­proach­es key stage of ap­proval process

Almost a year and a half after DBV Technologies pulled its peanut allergy immunotherapy patch from FDA review, the biotech will get their day in court. The FDA has scheduled an advisory committee hearing for May 15.

In the two-horse race to develop the first immunotherapy for peanut allergy, DBV had the early lead, filing an NDA for their patch in 2018. But on December 20 of that year, the company withdrew their application after, they said, meeting with regulators and determining they had not submitted “sufficient detail regarding data on manufacturing procedures and quality controls.” Aimmune filed their BLA 3 days later and won approval as the first immunotherapy for peanuts this month.

Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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An­to­nio Gual­ber­to starts post-Ku­ra ca­reer at Ei­sai sub­sidiary H3; eF­FEC­TOR co-founder Siegfried Re­ich jumps to Turn­ing Point

→ Days after Kura Oncology announced the departure of co-founder Antonio Gualberto, we finally know where he wound up. Eisai subsidiary H3 Biomedicine has recruited him as CMO to finding the right patients to its four clinical-stage small molecule assets hitting genomic drivers of cancer.

“Challenges of these and many other precision medicine approaches are on one hand technical, a need for robust and precise diagnostics, and in the other hand derived by the challenge to alter standard clinical practice in settings where patient screening, e.g. by tumor DNA sequencing, is not standard practice,” he wrote to Endpoints News on his way back to Boston from Eisai’s Tokyo offices. “Only compelling clinical activity can drive clinicians and pathologists to modify standard clinical practice.”

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Special report

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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