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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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US sup­ports ex­ten­sion for Covid-19 IP waiv­er de­ci­sion

After much debate, the US government is now calling for a deadline extension to discuss a controversial potential IP waiver for Covid-19 diagnostics and therapeutics.

Over the last five months, the Office of the United States Trade Representative said it has consulted with members of Congress, public health advocates, organized labor groups, academics, think tanks, companies and trade associations on the WTO’s recent TRIPS agreement, which established a 5-year waiver of certain patent requirements on Covid-19 vaccines.

Mar­ket­ingRx roundup: Phar­mas lay off Twit­ter ads for an­oth­er week; WPP un­cov­ers LGBTQ+ mar­ket­ing find­ings

When Twitter’s new owner Elon Musk tweeted this weekend, “Just a note to thank advertisers for returning to Twitter,” he likely wasn’t talking about big pharma companies. The vast majority of the top spending pharma advertisers had not returned last week, according to updated tracking data Pathmatic for Endpoints News.

Only three pharma advertisers spent any money at all, which is about the same as the past several weeks. AstraZeneca rejoined the active advertiser list, although at $700 spent hardly worth a personal Musk expression of gratitude. GSK remained active with $3,500 spent ad much lower than its previous spending, according to the Pathmatics data. Only Bayer spent any significant amount in advertising, with $244,000 spent last week, but that’s a considerable drop from almost $500,000 spent on OTC, prescription and corporate Twitter ads in each of the previous two weeks.

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Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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Bob Duggan, Summit Therapeutics co-CEO

Bounc­ing from ma­jor set­back, Sum­mit hands out $500M cash for can­cer drug — thanks to a loan from bil­lion­aire CEO

After hitting a dead end with Summit Therapeutics’ lead program, Bob Duggan has found the drug that he believes will usher into a compelling second act. So compelling, in fact, that it involves $500 million cash — and he’s taking money out of his own pocket to fund the deal.

Striking a partnership with Akeso Therapeutics out of China, Summit is bringing in a bispecific antibody that blocks both PD-1 and VEGF called ivonescimab. Akeso, which has a PD-1/CTLA-4 bispecific approved in China, has already taken ivonescimab into multiple clinical trials, including a Phase III in lung cancer.

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Gilmore O’Neill, Editas Medicine CEO

Ed­i­tas re­ports ear­ly-stage da­ta from two pa­tients in sick­le cell dis­ease

One company is moving forward in its bid to make a cell therapy for sickle cell disease viable — and after previous setbacks, including a hold earlier this year, execs are touting some really early data.

Editas Medicine announced Tuesday morning that it had positive safety and efficacy data from two patients in a Phase I/II trial investigating EDIT-301, a cell therapy candidate that Editas developed. Safety was measured in both patients, and efficacy data are from only the first patient dosed.

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Jonathan Montagu, HotSpot Therapeutics CEO

Ab­b­Vie puts up $40M to li­cense a treat­ment from HotSpot Ther­a­peu­tics

HotSpot Therapeutics has managed to gain some steam financially in the past few years, as the company wrangled several multi-million dollar raises. But its latest deal not only puts more cash into its pockets, it also connects with a major name in pharma.

On Tuesday, AbbVie and HotSpot announced they have entered an “exclusive” global collaboration, with the option to license HotSpot’s IRF5 program, which is designed to treat autoimmune diseases. The deal will see AbbVie hand HotSpot $40 million upfront, with the biotech eligible to receive $295 million in “option fees” and R&D milestones.