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.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

George Yancopoulos (Regeneron)

Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

Dan Gold, MEI Pharma CEO

De­vel­op­ment part­ners at MEI, Helsinn dump a high-risk PhI­II AML study af­ter con­clud­ing it would fail sur­vival goal

Four years after Switzerland’s Helsinn put $25 million of cash on the table for an upfront and near-term milestone to take MEI Pharma’s drug pracinostat into a long-running Phase III trial for acute myeloid leukemia, the partners are walking away from a clinical pileup.

The drug — an HDAC inhibitor — failed to pass muster during a futility analysis, as researchers concluded that pracinostat combined with azacitidine wasn’t going to outperform the control group in the pivotal.

Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.

Jan van de Winkel, Genmab CEO

Seat­tle Ge­net­ics, Gen­mab turn on TV for a high­light reel in cer­vi­cal can­cer — but a ri­val biotech promis­es a bet­ter show

Seattle Genetics $SGEN and their partners at Genmab $GMAB polished up some positive Phase II numbers for their antibody drug conjugate tisotumab vedotin — you can call it TV — for recurrent cervical cancer. And while they mapped out a shortcut to a potential quick approval, the big challenge for this team is being presented by a rival biotech which muscled its way into the spotlight for the same indication a year ago.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,600+ biopharma pros reading Endpoints daily — and it's free.