Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s lat­est at­tempt at se­cur­ing ap­proval for its oral testos­terone drug has fiz­zled yet again.

The Utah-based drug de­vel­op­er on Mon­day said the FDA has spurned its mar­ket­ing ap­pli­ca­tion, in­di­cat­ing that some ef­fi­ca­cy da­ta on the drug, Tlando, was not up to scratch to treat male hy­pog­o­nadism, a con­di­tion char­ac­ter­ized by low pro­duc­tion of the hor­mone testos­terone, which is re­spon­si­ble for main­tain­ing mus­cle bulk, bone growth, and sex­u­al func­tion.

Shares of the Salt Lake City com­pa­ny $LPCN cratered more than 69% to 84 cents in morn­ing trad­ing.

Testos­terone treat­ments such as skin patch­es, short-act­ing in­jec­tions, and top­i­cal gels are cur­rent­ly on the mar­ket. The space is well cov­ered by in­sur­ers and is grow­ing, gen­er­at­ing some 7.2 mil­lion pre­scrip­tions last year, ac­cord­ing to Cowen an­a­lysts. But their pop­u­lar­i­ty in the ag­ing male de­mo­graph­ic has be­come a prob­lem for some biotechs in the field, with reg­u­la­tors re­ject­ing a num­ber of ap­pli­ca­tions in re­cent years.

In­tra­mus­cu­lar in­jec­tions are of­ten the first-line testos­terone re­place­ment ther­a­py (TRT) modal­i­ty due to the fact that they have long been gener­ic, be­fore grad­u­at­ing to the brand­ed top­i­cal prod­ucts (or even the gener­ic top­i­cals, which car­ry on­ly mod­est dis­counts to brand­ed An­dro­Gel), the Cowen an­a­lysts wrote in April. “The top­i­cal prod­ucts such as Ab­b­Vie’s An­dro­Gel and Lil­ly’s Ax­iron ap­pear to be read­i­ly ac­cessed, de­spite their brand­ed/brand­ed gener­ic pric­ing.”

Tlando is de­signed to avert the is­sues that plague the ex­ist­ing top­i­cal and in­jectable prod­ucts. Lipocine’s big ri­val, Clarus Ther­a­peu­tics, in March, won FDA ap­proval for its oral prod­uct, Jaten­zo. Lipocine and Clarus have been locked in lit­i­ga­tion re­lat­ed to in­tel­lec­tu­al prop­er­ty as­so­ci­at­ed with their re­spec­tive ther­a­pies.

Months ago, Lipocine said a tri­al is set to be­gin in Au­gust 2020 as part of its patent in­fringe­ment law­suit against Clarus’s Jaten­zo, re­lat­ing to six of Lipocine’s U.S. patents.  In the mean­time, Lipocine plans to seek a per­ma­nent in­junc­tion for Clarus’s al­leged in­fringe­ment.

Lipocine has been scarred time and time again in its bat­tle to bring Tlando to mar­ket. The com­pa­ny re­ceived its first re­jec­tion from the FDA in 2016, about a year af­ter the agency tight­ened its scruti­ny of TRT prod­ucts in gen­er­al. The reg­u­la­tor in March 2015 asked man­u­fac­tur­ers to tweak their la­bels to re­flect that TRT prod­ucts are on­ly ap­proved for men with cer­tain med­ical con­di­tions, and not for ag­ing-re­lat­ed low testos­terone; and that da­ta sug­gest TRT use leads to an in­creased risk of heart at­tacks and strokes.

In 2016, the agency in­di­cat­ed it was not com­fort­able with the Tlando dos­ing al­go­rithm. “The pro­posed titra­tion scheme for clin­i­cal prac­tice was sig­nif­i­cant­ly dif­fer­ent from the titra­tion scheme used in the Phase 3 tri­al lead­ing to dis­cor­dance in titra­tion de­ci­sions be­tween the Phase 3 tri­al and re­al-world clin­i­cal prac­tice,” Lipocine cit­ed the FDA say­ing in a state­ment.

Lipocine re­sub­mit­ted a mar­ket­ing ap­pli­ca­tion in 2017. In an FDA staff re­view that fol­lowed in 2018, the agency said it had rec­om­mend­ed that the com­pa­ny con­duct a new Phase III tri­al that tests the dose titra­tion scheme pro­posed for mar­ket­ing. In­stead, Lipocine chose to con­duct two new sin­gle-arm late-stage tri­als, each test­ing a dif­fer­ent dose of Tlando (150 mg thrice-dai­ly and 225 mg twice-dai­ly) with­out titra­tion. The 150 mg tri­al failed, but the 225 mg dose made the cut.

FDA pan­elists al­so ex­pressed oth­er con­cerns, in­clud­ing that the orig­i­nal late-stage tri­al up­on which Lipocine had based its ap­pli­ca­tion on did not meet one or none of the three sec­ondary end­points that as­sess for un­ac­cept­ably high max­i­mal ex­po­sures to testos­terone; the drug’s im­pact on the pa­tient’s blood pres­sure and heart rate; and whether Tlando was def­i­nite­ly restor­ing testos­terone and its ma­jor metabo­lites in­to nor­mal range.

Days lat­er, an in­de­pen­dent pan­el of ad­vi­sors to the FDA al­so sug­gest­ed their dis­com­fort with the drug. Over­all, thir­teen pan­elists vot­ed against the ben­e­fit/risk pro­file of Tlando, while six vot­ed in fa­vor. Un­sur­pris­ing­ly, the FDA hand­ed Lipocine an­oth­er re­jec­tion.

So Lipocine con­duct­ed an­oth­er study, a small 24-pa­tient tri­al to de­fin­i­tive­ly show that the drug was de­fin­i­tive­ly restor­ing testos­terone lev­els, us­ing tri­al pro­to­col the FDA was look­ing for. But on Mon­day, the FDA’s CRL flagged a prob­lem the com­pa­ny had failed to deal with from the start: that the orig­i­nal ef­fi­ca­cy tri­al failed to show the drug clear­ing three sec­ondary end­points for max­i­mal testos­terone con­cen­tra­tions.

The com­pa­ny plans to meet with the agency to fig­ure out its next steps.

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

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Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

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Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

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Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

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FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

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Paul Biondi (File photo)

Bris­tol-My­er­s' strat­e­gy, BD chief Paul Bion­di ex­it­ed the com­pa­ny — just ahead of the $74B Cel­gene deal close

Paul Biondi, who orchestrated billions of dollars in deals for Bristol-Myers Squibb over the 5 years he’s run their business development team, has exited the company. Biondi left last month, according to a company spokesperson, in pursuit of another — unspecified — external opportunity.

After 17 years with Bristol-Myers Squibb, Paul Biondi, Head of Strategy and Business Development, decided to leave the company to pursue an external opportunity. The company wishes him well in his new endeavors. Bristol-Myers Squibb  is actively searching for Paul’s successor, and will make an announcement, as appropriate.

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Arie Belldegrun at UKBIO 2019. Shai Dolev for Endpoints News

Kite Phar­ma's ex-CEO con­tra­dicts founder as CAR-T patent tri­al heats up, with con­flict­ing val­u­a­tions

Two days after Kite Pharma founder Arie Belldegrun told a federal courtroom that a meeting he had with a Memorial Sloan Kettering executive wasn’t about licensing their immunotherapy patent, Kite’s ex-CEO Aya Jakobovits said it was.

The admission came Tuesday during cross-examination in a patent infringement case that features two of the biggest cancer biotechs and some of the most well-known names in American medicine.

Jakobovits initially said she was not in attendance, didn’t know it was going to happen and didn’t know what took place, according to Law360. But then the plaintiff’s lawyer handed her a document – whose contents were not publicly revealed – and asked again if she learned after-the-fact that the meeting involved a potential patent license.

“Yes,” Jakobovits eventually said.

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On the heels of promis­ing MCL da­ta, Kite hus­tles its 2nd CAR-T to the FDA as the next big race in the field draws to the fin­ish line

Three days after Gilead’s Kite subsidiary showed off stellar data on their number 2 CAR-T KTE-X19 at ASH, the executive team has pivoted straight to the FDA with a BLA filing and a shot at a near-term approval.

In a small, 74-patient Phase II trial reported out at the beginning of the week, investigators tracked a 93% response rate with two out of three mantle cell lymphoma patients experiencing a complete response.

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