Analysis Focus: SAGE
Sage Therapeutics (SAGE) will follow an accelerated plan to develop its GABA modulator SAGE-217. This follows an earlier Breakthrough Therapy meeting with the FDA. The candidate is being tested on conditions of major depressive disorder (NYSEARCA:MDD) and postpartum depression (NYSE:PPD).
Earlier in May, Brexanolone IV (SAGE-547), Sage's lead product candidate, an intravenous formulation of brexanolone for the treatment of PPD, received FDA Priority Review status. PDUFA is set on December 19, 2018. If approved, brexanolone IV may become the first and only medication indicated for the treatment of PPD. Recent developments regarding SAGE-217 makes the company's lead in the category even stronger.
Due to the successful Breakthrough Therapy meeting only a single additional Phase 3 study in MDD and the ongoing Phase 2 study in PPD will be sufficient to provide key data to support a U.S. marketing application. Phase2 PP trial data is expected by Q4 while Phase 3 MDD study will launch in H2.
All recent data show a very high rate of prevalence of MDD among various cross sections of US populations. The condition is often manifested in incidence of anhedonia, depressed mood, or feeling of hopelessness and meets five of the 9 DSM-5 MDD criteria. The lifetime prevalence of MDD was 20.6%. According to a study published in JAMA Psychiatry, approximately half of lifetime cases of MDD were considered severe (49.5%) and 39.7% were moderate in nature.
It is almost impossible to determine the rate of incidence of PPD. However, it is estimated that approximately 70%- 80% of women experience some form of baby blues and many more go through a more severe condition of postpartum depression and its other subtypes. ~4 million live births/year occur in the U.S. That takes the possible number of postpartum depression diagnoses to ~600K individuals. There are no approved therapies for PPD, and there is a clear unmet medical need for treatment. In recognition of that, Brexanolone IV had received Breakthrough Therapy Designation in September 2016.
Sage had a follow on offering in February 2018. The offer garnered the company ~$1.1 billion in cash. Though the accelerated development plan shortens the last stage trials considerably, SAGE-217 still has quite some length to complete. However, the cash position compared to the existing and projected burn rate does not face the prospect of near-term cash crunch. Seemingly for SAGE there are no serious catalysts on the way before the end of the year and that should allow the stock to have even more room. In spite of its ~20% increase to $175.76 yesterday, the stock is still behind its 52 wk high of $195.97. This seems to be a buy proposition ahead of the PDUFA.
Stocks in the News: GSGTF, AZN, LLY
Discussion: GenSight Biologics (OTC:GSGTF) reported additional results from Phase III clinical trial evaluating the safety and efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4). The candidates was tested in 37 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy (LHON) commenced between 6 and 12 months prior to study treatment. Earlier top-line results failed to meet primary endpoints in April. The same trial successfully met secondary endpoints. The company presented the full set of data and offer post hoc findings at a Key Opinion Leader Event in New York City. Following trial protocol all 37 subjects will be tested again at 96 weeks, and accordingly new data set will be reported in Q1 2019.
LHON is a condition in which bilateral, painless subacute loss of central vision occurs during young adult life. Symptoms begin early and usually in one eye. This is followed a few weeks later by visual failure in the other eye. In extremely rare cases neurologic abnormalities, such as peripheral neuropathy, postural tremor, nonspecific myopathy, and movement disorders may also occur. This rare disease is caused by mutations in mitochondrial DNA and it is transmitted by maternal inheritance. LHON affects ~1:50,000 people. Many carriers of the disease does not suffer from any visual loss.
Discussion: An independent data monitoring committee determined that both the late studies of lanabecestat were unlikely to meet the primary endpoints of the trial. Lanabecestat is a BACE inhibitor for the treatment of Alzheimer's disease (AD). AstraZeneca (NYSE:AZN) and Eli Lilly (NYSE:LLY) were developing the candidate. This is the third in the recent chain of setback for development of BACE inhibition. Apparently, the therapy development is facing a rough patch in recent times. Earlier, Johnson & Johnson (NYSE:JNJ) and Merck (NYSE:MRK) had bailed out their candidates atabecestat and verubecestat, respectively. The former was abandoned due to toxicity concerns while the latter had no definite efficacy data to continue.
AD is the leading contributor (accounting for up to 75% of all cases of dementia) to the global phenomenon of dementia among the elderly. Many consider the disease to be reaching an epidemic proportion. As the projected elderly population is expected to see a rise to 12% of the total population and touching ~1B in 2030, AD remains at the core of the concern for the elderly. Hence any significant pharmacological development in improving the conditions of AD has a significantly long term impact. Having said that, this one negative component in AZN and LLY's long and strong pipeline doesn't really dent either of the stock's standing.
In Other News
Pluristem Therapeutics (NASDAQ:PSTI) announced positive data from a Phase 2 clinical trial that met the primary endpoint of a statistically valid change from baseline for its candidate PLX-PAD on patients with intermittent claudication (IC). IC is a type of peripheral arterial disease. Another ongoing Phase 3 trial on critical limb ischemia is expected to complete in May 2020.
Phase 2 clinical trial of Idera Pharma's (NASDAQ:IDRA) IMO-8400 on adult patients with dermatomyositis failed to achieve primary endpoint. Dermatomyositis an autoimmune disorder characterized by muscle weakness and skin rash.
Part B of Nano cap vTv Therapeutics (NASDAQ:VTVT) Phase 3 trial assessing azeliragon in people with mild Alzheimer's disease failed to achieve the co-primary endpoints. The company plans to discuss the data with the FDA to clarify an accelerated approval pathway
Tyme Technologies (NASDAQ:TYME) released patient data on its lead candidate SM-88 for anti-tumor effect across range of cancers. The objective response rate in 83 evaluable patients from the First Human Study and Compassionate Use Program were varied across various types of cancer.
RTI Surgical (NASDAQ:RTIX) announced full commercial launch of Fortilink TS and LIBF systems. These adds to the list of devices used for interbody fusion featuring TETRAfuse 3D technology.
EMA's CHMP will accept an oral hearing of Puma Biotech's (NYSE:PBYI) to present its rationale for a re-examination of its marketing application for neratinib for HER2-positive breast cancer.
Merck's KEYTRUDA (pembrolizumab) for the treatment of patients with recurrent/metastatic cervical cancer receives FDA approval.
Privately held PneumRx's marketing application seeking approval for its ELEVAIR Endobronchial Coil System for use in emphysema patients to improve lung function, exercise capacity and quality of life will face FDA AdCom on June 14.
Artelo Biosciences (OTCQB:ARTL) and Syngene International Ltd finalized an R&D agreement to develop ART27.13, a Phase 2-stage dual cannabinoid agonist, for cancer indications, including cancer-related anorexia and weight loss.
Aevi Genomic Medicine (NASDAQ:GNMX) decide to increase the sample size of its Phase 2 trial evaluating AEVI-001 in pediatric and adolescent patients with mGluR mutation-positive attention deficit hyperactivity disorder. The increase in size will increase statistical powering.
Protalex (OTCQB:PRTX) reported on its preclinical action in which its lead candidate PRTX-100 reduced disease activity in a second confirmatory mouse study in myasthenia gravis, an autoimmune disorder characterized by weakness in the skeletal muscles.
Diffusion Pharmaceuticals (NASDAQ:DFFN) announced a European patent grant that covers oral formulations of bipolar trans carotenoids. The group includes its lead drug trans sodium crocetinate.
Moleculin Biotech (NASDAQ:MBRX) announced agreement with a Polish University to develop STAT3 inhibitor for ocular tumors. The candidate with an Orphan Drug indication qualifies for accelerated review in the U.S. and elsewhere.
Albireo Pharma (NASDAQ:ALBO) announced FDA grant of granted Rare Pediatric Disease Designation for lead drug A4250 for the treatment of a rare life-threatening liver disease called progressive familial intrahepatic cholestasis.
ProQR Therapeutics N.V. (NASDAQ:PRQR) concludes agreement to collaborate with EB EB Research Partnership (EBRP) and EB Medical Research Foundation (EBMRF) to develop QR-313 for patients with dystrophic epidermolysis bullosa caused by mutations in exon 73 of the COL7A1 gen. Both EBRP and EBMRF are non-profit organizations.
Chimerix (NASDAQ:CMRX) announced positive preclinical data on CMX521 for the treatment of acute gastroenteritis caused by noroviruses. The candidate is now Phase 1 development.
Surface Oncology (NASDAQ:SURF) announced that Novartis has started Phase 1 clinical trial of its SRF373 ('NZV930) in a range of cancers. Novartis is the global licensee of the candidate. SRF373 is the second pipeline candidate of SURF to make it to the clinic this year.
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I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.