Abbvie Inc (ABBV)

[Just the facts maam]

Thanks DewDilligence, you are most likely right about Androgel, but I found it odd that they had a 48 month estimated completion for their trial though having 60 month time frame. At the very least the estimated completion date should have been June 2023. Though the time to Major Adverse Cardiac Event is the primary outcome and they are looking a cardiovascular a nd prostate cancer safety. The trial is also looking at other indications including: sexual activity, depression, bone fractures and anemia diabetes.

As for Libigel, there appears to be more to the story. As you stated it did fail to show efficacy for HSDD due to a large placebo effect. But the larger safety trial was also measuring efficacy and had a surgically menopausal population similar in size to the total of the two pivotal efficacy trials. They efficacy her was being measured in similar method used in the Intrinsa trials. The results form this trial have yet to be released. Secondary outcomes for this trial were never disclosed, as well.

It is true that ABBT/ABBV have never publicly owned or expressed an interest in female testosterone. However, I and a few others can attest to the fact that Dr. Michael Snabes' Linkedin profile, at one time, stated that he worked for AbbVie as early as January 2013 while working for Biosante at the same time. His linked in work history now reads as if there was no overlap, with him starting at AbbVie in April 2013.

Additionally up until, ATRS was issued a patent for using Testosterone to treat HSDD, ABBT was seeking a similar patent.

Dr. Snabes discovered that Libigel reduced Cardiovascular events over placebo ( never publicly disclosed). It appears that Libigel safety/efficacy trial or at least the observation of the 3,656 participants went beyond the December 2012 completion date. This became evident on December 19, 2015, when during the patent prosecution for reducing cardiovascular events (Dr. Snabes as inventor) they added the claim that restoring testosterone also reduced breast cancer events. In September 2012, the reduction in breast cancer events by restoring testosterone was not present. Interestingly, the support for the claim that it reduced cardiovascular events is well documented in the specifications of their patent application, but there is no such support for the breast cancer reduction claim. If ANIP had continued the work to make such a claim they would likely provided the supportive information to their claim in the specifications document accessible through the Public Pair. It also would have shown up in their R&D expenses as ANIP is a smaller company and it would be hard to hide the expenses related the follow-up of the participants.

According to the American Heart Journal article titled "A cardiovascular safety study of LibiGel (testosterone gel) in postmenopausal women with elevated cardiovascular risk and hypoactive sexual desire disorder" which also credits Dr Snabes.

Study procedures

There are 9 clinical visits and 14 telephone contacts during the course of the study (Figure 1). Office visits will occur at screening and randomization and at 3, 6, and 12 months postrandomization and yearly thereafter. Telephone contacts will be completed at week 6, month 9, and at 3-month intervals unless a clinical visit is required. Subjects are instructed to contact sites if they believe that they have experienced a CV event or breast cancer. At each scheduled contact, participants are asked about adverse events and health care and hospitalizations; questioned about specific androgenic side effects, potential CV events, and breast cancer; and undergo other assessments of safety and tolerability as well as laboratory measures.

Efficacy will be evaluated at office visits and telephone contacts using the Subject Global Assessment and Perception of Benefit Questions.Participants who discontinue study drug will be encouraged to complete all study visits, examinations, and questionnaires and to report potential CV events and breast cancer.


Breast and endometrial safety examinations

Breast examination and mammography will be performed at baseline and annually. Endometrial biopsy will be performed at baseline and at study years 1, 2, and 5. Participants with vaginal bleeding will undergo uterine evaluation that includes an endometrial biopsy. Study medication will be discontinued in participants with evidence of uterine cancer, complex or adenomatous hyperplasia, or atypia.

The 3,656 participant trial was an adaptive trial under an FDA Special Protocol Assessment set up in two parts, the first part being pre-commercialization. For which Biosante appears to have met.

ANIP has deflected or stopped responding to shareholder questions related to Libigel development since 2016. The full 5 year, 3,656 participant study would have been completed in August 2016. The Certification/Extension request to delay submission of results on October 27, 2021, is puzzling, unless an NDA has been filed or was about to be filed by a company other than ANIP. Logic dictates that if an NDA is being filed, AbbVie with Dr Snabes, would have been in the best position to take the first FDA approved female testosterone product across the finish line. Especially since AbbVie now owns the Intrinsa data.

Is Libigel's safety/efficacy data, supported by Intrinsa's trial data and the Global Consensus Position Statement on the Use of Testosterone Therapy for Women enough to support an approval?

The position statement issued in September 2019, provides guidelines in administering testosterone considered to be a benchmark. It provides clinical guidance regarding the use of testosterone therapy in women, examining the effect on sexual function; well-being, mood, and cognition; musculoskeletal effects; cardiovascular and breast health; as well side effects and adverse events. This is first time expert global agreement has been provided on how testosterone should be measured in women and how it should be therapeutically prescribed.

The Position Statement is largely based on the findings of the Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomized controlled trial data. The study reviewed 36 clinical trials (excluding all phase 3 LibiGel clinical trials), involving 8,480 participants in total. The Position Statement found that though no established indications for testosterone therapy for women existed, clinicians have been treating women with testosterone for decades, uncertain of the benefits and the risks. In most countries, including the United States, testosterone therapy is prescribed off-label male testosterone or compounded therapies. They also found that further investigation is warranted with respect to an individual's well-being, musculoskeletal and cognitive health and long-term safety. (LibiGel should address the long-term safety issue when the trial data is finally published.)

The Position Statement has been endorsed by the following organizations:

The International Menopause Society,
The Endocrine Society,
The European Menopause and Andropause Society,
The International Society for Sexual Medicine,
The International Society for the Study of Women's Sexual Health,
The North American Menopause Society,
The Federacion Latinoamericana de Sociedades de Climaterio y Menopausia,
The Royal College of Obstetricians and Gynaecologists,
The International Society of Endocrinology,
The Endocrine Society of Australia, and
The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

According to the Position Statement, testosterone should only be used to treat HSDD after other options have not proved beneficial and testing shows that a women is testosterone deficient. It only recommends transdermal or cream applications. Where an appropriate approved female testosterone preparation is not available, off label, prescribing of an approved male formulation is considered reasonable. It does not recommend injectables, pellets or formulations that result in supraphysiological blood concentrations of testosterone, or compounded testosterone.

In the end AbbVie may not be interested in female testosterone. But they appear miles ahead of any competition should they want to enter a market with potentially no competition until December of 2033.