Upcoming FDA PDUFA: Oct 3 2013 - Ligand Pharmaceuticals and Pfizer - Aprela (Duavive) for menopause

Ligand Pharmaceuticals (LGND) and Pfizer (PFE) are awaiting an FDA drug approval decision for Aprela - a novel combination drug of Bazedoxifene and Conjugated estrogens (Premarin) for the treatment of moderate-to-severe vasomotor symptoms (VMS) and vulvar and vaginal atrophy (VVA) associated with menopause, as well as the prevention of postmenopausal osteoporosis in non-hysterectomized women.

Date of FDA Decision (PDUFA): October 3, 2013
Company name: Ligand Pharmaceuticals and Pfizer
Stock ticker: LGND and PFE
Location: La Jolla, CA

Type of application: First NDA Submission; combination of an approved and an un-approved drug
Name of drug: Aprela

Indication: moderate-to-severe vasomotor symptoms (VMS) and vulvar and vaginal atrophy (VVA) associated with menopause, as well as the prevention of postmenopausal osteoporosis in non-hysterectomized women 

Ligand Pharmaceuticals: 01 Oct 2013

Market Cap	$884.64 Mln
52-week range	14.75 – 50.85
Avg. volume	262,502

Q1 2013:

Net Income	$0.30 per share
Cash	$10.1 mln

Ligand is a biopharmaceutical company that develops and acquires assets it believes will generate royalty revenues and produce sustainable profitability. Ligand has a diverse asset portfolio addressing the unmet medical needs of patients for a broad spectrum of diseases including thrombocytopenia, multiple myeloma, diabetes, hepatitis, muscle wasting, dyslipidemia, anemia, and osteoporosis. Ligand has established multiple alliances with the world's leading pharmaceutical companies including GlaxoSmithKline, Merck, Pfizer, Eli Lilly & Company, Baxter International, Bristol-Myers Squibb, Celgene, Onyx Pharmaceuticals, Lundbeck Inc., and The Medicines Company, among others.

As a result of a series of successful licensing agreements, Ligand’s total revenue more than doubled in recent years, with royalties up 90% on higher sales of GlaxoSmithKline’s Promacta® and a contribution from Onyx Pharmaceuticals’ Kyprolis™, plus increases of 131% and 125% in sales and licensing revenues of Ligand’s proprietary patented drug delivery technology Captisol.

Aprela is a drug which combines Pfizer’s as-of-yet-unapproved drug Viviant (bazedoxifene), initially developed by Ligand and Wyeth (now Pfizer) in 1994 and Premarin, Pfizer’s conjugated estrogen compound. Bazedoxifene is a selective estrogen receptor modulator, which is a compound able to selectively act on estrogen receptors throughout the body. Aprela belongs to the novel class of tissue-selective estrogen complexes (TSECs), which pair SERM with conjugated estrogen (Premarin). So far, the combination drug has demonstrated positive efficacy and safety results in a series of Phase III clinical trials involving approximately 7,500 women.

The FDA accepted an NDA from Pfizer and Ligand in December 2012. The agency will deliver its verdict on Oct 3, 2013, but complications are expected, in light of the fact that bazedoxifene has been encountering obstacles with FDA approval since 2007. 

Click here for a free report on the upcoming PDUFA stock catalysts in 2013.

Interview with Professor Idan Segev, Israel's leading neuroscientist and head of Human Brain Project (HBP) Simulation Platform, researcher at Hebrew University

Prof. Segev is known as one of Israel’s most prominent and enthusiastic neuroscientists, whose oft-quoted motto “Attack the Brain” is in fact a fair embodiment of his research aspirations. Segev forewent many commercial seductions and lucrative management roles in pursuit of his passion in research. He has spent no less than several decades on Hebrew University’s Givat Ram campus, where he received his bachelor’s degree in mathematics and biology, his Master’s of Science degree in neurobiology and his doctorate in experimental and theoretical neurobiology.

Along with a 6-strong force of PhD. students, Segev is currently working on elucidating a versatile array of grey matter’s enigmas with a mathematical touch, from how the brain computes information and how synapses are formed to the sets of rules which guide this formation in healthy and ailed brains. For him, the pinnacle of this research would be an effective ability to simulate our findings in a working computational model. But for this to succeed, he says, we must truly “attack the brain” from all directions, which would require a combined effort on the part of an immense plethora of experts hailing from all doctrines.

This is why Prof. Segev, a personal friend of Human Brain Project’s Henry Markram and one of the original participants in the HBP’s prototype Blue Brain, seemed to fit like a puzzle piece into the mind-set of EU’s colossal initiative. He was chosen to lead the Simulation Platform project of HBP, and his Hebrew University lab was one of 130 initially selected to lay the foundations for the assignment. Perhaps rather modestly for a researcher in such a costly field as neuroscience, Prof. Segev says the €130,000 over 30 months which was isolated for his lab’s research by HBP will be perfectly sufficient to make significant progress. Dashing new facilities and a few more PhD students at HU’s new Edmund and Lily Safra Brain Centre, which began construction in May of 2013, will certainly help. As he jokes about the new sound-proof windows just installed in his current office, Prof. Segev says he is immensely excited about observing the stone-throw-away construction of the new center over the next three years, which he personally helped design.

Brushing off HBP opponents’ fears about the difficulty of processing the massive amounts of data collected from thousands of facilities around the globe which the HBP aims to tackle, Prof. Segev brings up the example of the terabytes of data generated by star observation, which has been managed extremely well once solid, standardized models were in place. Neuroscientists are by no means oblivious of this problem, and huge initiatives to devise complex statistical models and collaborative software are underway. Global cooperation, however, is a crucial key to HBP’s progress. This is why the project has been sliced up into so many research layers: whilst Segev’s lab is working on elucidating inter-neuronal physiological behavior, a lab in Edinburgh University headed by Prof. Seth Grant is working on mapping the thousands of molecules innate to the brain, at the same time as a leading Institute Pasteur neuroscientist slash philosopher Jean-Pierre Changeux is exploring the relationship between the physical brain and the cognitive mind. Eventually, superimposing the findings of these various “HBP Pillars” will lead to an altogether new map of the brain where hundreds of parameters can be tied together to from an altogether new understanding of the neuronal microcosm.

Speaking about the global neurotechnology environment, Prof. Segev says that he has very little faith in Big Pharma’s strides to develop neurological drugs, particularly because such painful blows have been sustained by the industry in CNS developments in recent years. He says that there is no future for neuropharmaceuticals in Big Pharma, certainly not for the way in which these companies conduct drug discovery research. Rather, he says, for the time being medical devices will become clear leaders in the neuro-therapeutic field, until (his) research yields more insight into the underlying causes of brain disease.

On President Peres’s initiative to brand Israel as a neuro-hub, Prof. Segev says this important mission by Israel’s “awesome President” is set for none other than success, as there is one thing one can trust in Israel, and that is the insatiable curiosity and strong determination to learn, which seemingly drives this nation forward. Segev’s only one wish, however, would be to lift the political barriers here and to unleash the brain power of the region which, in his opinion, hides unbelievable potential.

A question about whether he has any commercial interests the Professor interposes with a categorical “no”. “Who needs money”, he says, “when everything I need is already in my head?”

Kythera Biopharmaceuticals - A Buyout Target Following Phase III Results

Original Seekingalpha article can be found here 

Last night (Sep 16, 2013), after trading hours, Kythera Biopharmaceuticals (KYTH) announced positive top line results from its Phase III studies with ATX-101 for the reduction of submental fat. The REFINE-1 and REFINE-2 Phase III trials met all primary and secondary endpoints and reaffirmed the efficacy and safety of ATX-101 for the reduction of submental fat, commonly referred to as a double chin.

Focused on development and commercialization of products for the aesthetic medicine market, Kythera is led by a highly experienced management team, boasting impressive record in the pharmaceutical industry and the aesthetic medicine market, as former Allergan (AGN) and Amgen (AMGN) executives. Kythera has been flying under the radar since its October 2012 IPO, and the successful completion of the Phase III program is expected to bring KYTH to the front, and in our opinion, makes it a buyout target.

Kythera's ATX-101 is a proprietary synthetic formulation of sodium deoxycholate, a naturally occurring secondary bile acid, which destroys fat cells when injected subcutaneously into the target fat, while leaving surrounding tissue largely unaffected. ATX-101 has been developed as a treatment for the reduction of submental fat via administration of a series of microinjections into the submental area for up to six treatment visits at least 28 days apart.

ATX-101 is aimed at replacing the current, highly invasive, alternatives - liposuction, chin lifts and chin implant surgeries - which have been gaining immense popularity lately. If approved, ATX-101 will be the first and only drug product for the reduction of submental fat, with the potential to reach annual sales of $500 million in the United States alone, according to the company.

KYTH holds a collaboration agreement with Bayer's (BAYRY.PK) dermatology division to develop and commercialize ATX-101 outside the United States and Canada, and is eligible to receive up to $297m in additional regulatory and commercialization milestones, as well as escalating sales royalties in mid to high-teens. Bayer completed two pivotal Phase III trials of ATX-101 in Europe for the reduction of submental fat. During June 2012, Kythera released results from these studies, in which ATX-101 achieved a statistically significant reduction in submental fat based on clinician, patient and objective ratings.

The impressive phase III results presented by KYTH yesterday show improvement compared to data from previous clinical studies, which were impressive on their own. The table below summarizes the efficacy results of the REFINE-1 and REFINE-2 Phase III North American studies.

ATX-101 also proved safe and tolerable, as no treatment-related serious adverse events were recorded in the studies. The common adverse events were predominately transient and local to the treatment area.

	North American studies
	REFINE-1	REFINE-2
Trial design	- Up to 6 treatments at 28-day intervals. - ~1000 patients enrolled. - Primary assessment performed 12 weeks after last treatment.
Primary end-points
Proportion of Patients with ≥ 1 point simultaneous improvement in CR-SMRFS1 and PR-SMFRS2	70.3% vs. 18.7% (placebo) p<0.001	66.9% vs. 22.4% (placebo) p<0.001
Proportion of Patients with ≥ 2 point simultaneous improvement in CR-SMRFS1 and PR-SMFRS2	13.4% vs. 0% (placebo) p<0.001	18.7% vs. 0% (placebo) p<0.001
Secondary end-points
Volume reduction in the submental region (measured through MRI)	46% vs. 5.4% (placebo) p<0.001	40% vs. 5.1% (placebo) p<0.001
Change from baseline in PR-SMFIS3	3.63 vs. 1.14 (placebo) p<0.001	3.47 vs. 1.48 (placebo) p<0.001
1 5-point Clinician-Reported Submental Fat Rating Scale 2 5-point Patient-Reported Submental Fat Rating Scale 3 Patient-Reported Submental Fat Impact Scale (rating visual and psychological impacts)

The successful completion of the ATX-101 Phase III program, both in the EU and North America, represents the end of uncertainty regardingKythera. The notable and consistent efficacy, combined with a very positive safety profile, mean that regulatory approvals are expected without significant challenges. Submission of an MAA to the EMA by Bayer and an NDA to the FDA by KYTH are expected during Q1 of 2014, with marketing approvals in the beginning of 2015.

Right now, the only uncertainty is whether Kythera will be acquired. The company's extreme focus and the attractiveness of its sole product make it a very good buyout target. Add to that the partnership with Bayer, and the very tight connections Kythera executives have with Allergan, and the top two candidates are easy to spot.