Now that we are about halfway through October, there are several data releases likely to happen by the end of the month. We also have ESMO (European Society For Medical Oncology) coming October 19 – 23, CTAD (Clinical Trials on Alzheimer’s Disease) coming on October 25, 2018, and ACR (American College of Rheumatology) on October 19 – 24.
Love the chart and the surging large players volume with the break above the 200 day moving average. However, technically EARS stock does not present a decent entry opportunity at the moment. Prices have been extended to far to the upside lately. For a good entry, it is usually better to wait for a consolidation but with the October 17, catalyst fast approaching, a technical entry is less important. I like the chart for a speculative mad-money play.
AM-125 for Vertigo. Phase 1 data due October 17, 2018.
On October 12, 2018, Auris Medical Holding, a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in neurotology and mental health supportive care, announced that it will provide an update on its intranasal betahistine program, including key results from the second Phase 1 trial, on Wednesday, October 17, 2018. Following the announcement, Auris Medical’s management team will host a live conference call and webcast at 8:00 am Eastern Time (2:00 pm Central European Time).
To participate in this conference call, dial 1-877-407-0312 (toll free) or +1 201-389-0899, and enter passcode 13684198. A live webcast of the conference call can be accessed in the Investor Relations section of the Auris Medical website at www.aurismedical.com. A replay will be available approximately two hours following the live call.
Auris Medical is a Swiss biopharmaceutical company dedicated to developing therapeutics that address important unmet medical needs in neurotology and mental health supportive care. The company is focused on the development of intranasal betahistine for the treatment of vertigo (AM-125) and for the treatment of antipsychotic-induced weight gain and somnolence (AM-201). This program is currently in Phase 1. In addition Auris Medical has two Phase 3 programs under development: AM-111 for acute inner ear hearing loss and Keyzilen® (AM-101) for acute inner ear tinnitus.
TXMD stock does not present a quality technical setup at the moment. Price movement has been a little bit too volatile to find a nice entry and exit point. It is probably a good idea to wait for a consolidation first but with the October 28, 2018, PDUFA event approaching, technical analysis yields to fundamental catalyst analysis.
TX-001HR for moderate to severe vasomotor symptoms (VMS). PDUFA date October 28, 2018.
On March 8, 2018, TherapeuticsMD, an innovative women’s healthcare company, announced the acceptance of the NDA for TX-001HR by the FDA. TX-001HR is the company’s investigational bio-identical hormone therapy combination of estradiol and progesterone in a single, oral softgel for the treatment of moderate-to-severe vasomotor symptoms due to menopause.
The FDA in its 74-day letter stated that the application is sufficiently complete to permit a substantive review and that, at this time, the FDA has not identified any potential review issues. The FDA noted that the filing review is only a preliminary evaluation of the application and is not indicative of deficiencies that may be identified during the FDA’s review. The PDUFA target action date for the completion of the FDA’s review is October 28, 2018.
“The acceptance of the NDA for TX-001HR is another important milestone for TherapeuticsMD and reaffirms the strength and commitment of our organization,” said TherapeuticsMD CEO Robert G. Finizio. “If approved, TX-001HR has the potential to be the first and only combination of bio-identical estradiol and bio-identical progesterone in a single, oral softgel to meet the needs of patients, physicians, and pharmacies as an FDA-approved, third-party reimbursed treatment option for women suffering from moderate-to-severe vasomotor symptoms due to menopause.”
The 505(b)(2) NDA submission for TX-001HR is supported by the complete TX-001HR clinical program, including positive results of the phase 3 Replenish Trial, which evaluated the safety and efficacy of four doses of TX-001HR (1 mg estradiol/100 mg progesterone, 0.5 mg estradiol/100 mg progesterone, 0.5 mg estradiol/50 mg progesterone, 0.25 mg estradiol/50 mg progesterone) compared to placebo. The co-primary efficacy endpoints in the Replenish Trial were the change from baseline in the number and severity of hot flashes at weeks 4 and 12 as compared to placebo. The primary safety endpoint was the incidence of endometrial hyperplasia with up to 12 months of treatment. General safety was also evaluated. Both the 1 mg estradiol/100 mg progesterone and the 0.5 mg estradiol/100 mg progesterone doses achieved statistically significant and clinically meaningful results across the four co-primary efficacy endpoints. In addition, the incidence rate of endometrial hyperplasia was 0% across all doses with up to 12 months of treatment, meeting the primary safety endpoint of less than 1% incidence of endometrial hyperplasia.
TX-001HR is the company’s investigational bio-identical hormone therapy combination of estradiol and progesterone in a single, oral softgel for the treatment of moderate-to-severe vasomotor symptoms due to menopause.
Menopause is a natural life-stage transition for women with an average onset of 51 years. According to the United States Census Bureau, approximately 43 million women in the U.S. are of menopausal age (45-64 years).
As the ovaries stop producing hormones, levels of circulating estrogen decrease, often causing vasomotor symptoms (VMS) such as night sweats, hot flashes, and sleep disturbances. VMS affect as many as 60-80 percent of all menopausal women.
Menopausal women can benefit from hormone therapy (HT), also known as hormone replacement therapy (HRT), which is recognized by key medical societies as the most effective treatment for relief of symptoms related to menopause.
BIIB does present a nice setup opportunity. Prices have been consolidating lately. There is a resistance zone just above the current price starting at $338.02. Right above this resistance zone may be a good entry point. There is a support zone below the current price at $330.93, a stop order could be placed below this zone.
BAN2401 (Aβ mAb for Alzheimer’s disease. Phase 2 mixed data released July 25, 2018. High dose exhibited statistical improvement. Low doses missed. Update likely at CTAD October 25, 2018.
On July 25, 2018 Eisai Co., Ltd. and Biogen Inc. (BIIB) announced detailed results from the Phase II study (Study 201) with BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, in 856 patients with early Alzheimer’s disease as part of Session DT-01 “Recent Developments in Therapeutics” (Presentation number: DT-01-07) at the Alzheimer’s Association International Conference (AAIC) 2018 being held in Chicago, Illinois, United States on July 25. This abstract was accepted for Late Breaking oral presentation at AAIC.
Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized Phase II clinical study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain. Patients were randomized to five dose regimens, 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, or placebo. This study used a Bayesian Adaptive Randomization Design to automatically allocate newly enrolled patients into the study to treatment arms showing higher probability of efficacy based on the results of interim analyses.
The study assessed changes from baseline to 18 months in biomarkers measuring the underlying disease pathophysiology, including changes in amyloid accumulated in the brain as measured by amyloid PET (positron emission tomography). The clinical endpoints of Alzheimer’s Disease Composite Score (ADCOMS), Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Sum of Boxes (CDR-SB) were also assessed from baseline to 18 months of treatment.
Through Bayesian interim analyses, the highest doses of 10 mg/kg monthly and 10 mg/kg biweekly were determined to be the treatment dosages with higher efficacy early in the trial, and as a result, the proportion of patients allocated to these treatment arms was greater (placebo: 247 patients, 2.5 mg/kg biweekly: 52 patients, 5 mg/kg monthly: 51 patients, 5 mg/kg biweekly: 92 patients, 10 mg/kg monthly: 253 patients, 10 mg/kg biweekly: 161 patients). Following a regulatory request (outside of the United States) in July 2014, the allocation of APOE4 carriers to the 10 mg/kg biweekly treatment arm was restricted, resulting in fewer APOE4 carriers in this arm and more patients being allocated to the 10 mg/kg monthly treatment arm.
BAN2401 demonstrated a dose-dependent reduction in amyloid plaques as measured by amyloid PET, and this reduction was statistically significant at all doses. At the highest dose of BAN2401 (10 mg/kg biweekly), an analysis of amyloid accumulated in the brain using standardized PET as measured on the Centiloid scale showed an observed mean at baseline of 74.5 and at 18 months of 5.5. Using a Mixed-effects Model with Repeated Measures (MMRM), the mean reduction in amyloid load was 70 units, which was statistically significant (p<0.0001). In amyloid PET image visual read, BAN2401 demonstrated a dose dependent conversion from amyloid positive to negative, and at the highest dose, 81% of patients converted from amyloid positive to negative at 18 months (p<0.0001).
Conventional statistical methods on predefined clinical endpoints at the 18 month final efficacy time point confirmed a dose-dependent slowing in cognitive decline from baseline on ADCOMS. The highest treatment dose of 10 mg/kg biweekly demonstrated a statistically significant slowing of clinical decline of 30% compared to placebo at 18 months (p=0.034). A statistically significant slowing of decline on ADCOMS was observed as early as 6 months (p<0.05) as well as at 12 months (p<0.05). Dose-dependent slowing in cognitive decline from baseline on ADAS-Cog was also observed for BAN2401, with the highest treatment dose of BAN2401 demonstrating a significant slowing of clinical decline compared to placebo at 18 months (47% slower decline, p=0.017). Furthermore, dose-dependent slowing in cognitive decline from baseline on CDR-SB was observed, surpassing the pre-specified difference of 25% over the duration of the study. At 18 months, slowing of clinical decline for the highest treatment dose of BAN2401 compared to placebo on CDR-SB was 26%. The rate of clinical decline for the placebo group was consistent with the results of research by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) in the United States.
In a Bayesian analysis of ADCOMS at 12 months, the estimated probability that the highest dose of BAN2401 slows clinical decline more than placebo was 98%. While the criteria for early success at 12 months was pre-specified as an 80% or higher estimated probability of demonstrating a clinically significant difference (a 25% or greater slowing in clinical decline) from baseline compared to placebo, the actual probability for this criteria was 64% according to Bayesian analysis.
A dose-dependent increase in Aβ levels in cerebrospinal fluid (CSF) in patients on BAN2401 (highest dose at 18 months: p<0.0001) was observed. Combined analysis of patients receiving BAN2401 at 10 mg/kg (either monthly or biweekly) demonstrated a statistically significant reduction in total tau over time compared to placebo (p<0.05).
BAN2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration. The incidence rate of treatment-related adverse events was 26.5% for the placebo arm, 53.4% for the 10 mg/kg monthly treatment arm and 47.2% for the 10 mg/kg biweekly treatment arm. The most common treatment emergent adverse events were Amyloid Related Imaging Abnormalities (ARIA) and infusion-related reactions. Incidence of ARIA-E (edema) was 9.9% at the highest treatment dose, and not more than 10% in any of the treatment arms. Incidence of ARIA-E in APOE4 carriers was 14.6% at the highest dose. Per protocol, all patients presenting with ARIA-E on MRI were discontinued in the study. The incidence rate of serious adverse events was 17.6% for the placebo arm, 12.3% for the 10 mg/kg monthly treatment arm and 15.5% for the 10 mg/kg biweekly arm.
ESPR stock shows a decent setup pattern. Prices have been consolidating lately. There is a very little resistance above the current price. There is a support zone below the current price at $46.12, a stop order could be placed below this zone.
Bempedoic acid – CLEAR LDL-C Lowering Program 1002-047 for Hypercholesterolemia. Phase 3 data due October, 2018.
On August 27, 2018, Esperion announced positive top-line results from the pivotal Phase 3 bempedoic acid / ezetimibe combination pill study (1002-053). This trial was a randomized, double-blind, parallel group study conducted to evaluate the efficacy and safety of the bempedoic acid 180 mg / ezetimibe 10 mg combination pill compared to bempedoic acid, ezetimibe or placebo in patients treated with maximally tolerated statins.
This pivotal Phase 3, four-arm study design including a primary endpoint of LDL-C lowering, study statistics and an abbreviated 505(b)(2) regulatory pathway were discussed and agreed to with the U.S. Food and Drug Administration (FDA) in 2017.
The study included 382 high-risk patients taking maximally tolerated statins who required additional LDL-C lowering and met its key efficacy endpoints, including:
On-treatment analysis LDL-C lowering of 35 percent for the combination pill at 12 weeks (p<0.001) compared to 3 percent for placebo, 24 percent for ezetimibe 10 mg (EZE) and 20 percent for bempedoic acid 180 mg (BA);
In the intent to treat analysis, LDL-C lowering was 32 percent for the combination pill compared to 3 percent for placebo (p<0.001), 21 percent for EZE (p<0.001) and 18 percent for BA (p<0.001);
Reduction of 34 percent for the FDC in high-sensitivity C-reactive protein (hsCRP), an important marker of the underlying inflammation associated with cardiovascular disease, compared with an increase in placebo of 4 percent and reductions of 20 percent for BA and 9 percent for EZE.
In a post-hoc analysis of patients considered statin intolerant, the combination pill LDL-C lowering was 43 percent in the on-treatment analysis compared to a one percent increase for placebo;
“I’m pleased to see the positive safety and tolerability profile of the bempedoic acid / ezetimibe fixed-dose combination pill which was similar to that of ezetimibe alone,” said Christie M. Ballantyne, M.D., chairman of Esperion’s Phase 3 Executive Committee and Professor and Chief of Cardiology at Baylor College of Medicine in Houston. “The LDL-C lowering and hsCRP reductions seen with the combination are very important to physicians like me who see these challenging patients every day, and we need more options for them.”
Safety and Tolerability of Combination Pill Over 12 Weeks
In this 12-week study, the bempedoic acid / ezetimibe combo pill was observed to be safe and well-tolerated. The results showed no clinical differences between the FDC, BA, EZE and placebo patient groups in the occurrence of:
Serious adverse events (SAEs) with 8 percent, 6 percent, 9 percent and 2 percent, respectively. No SAEs were considered to be related to study medication;
Discontinuations due to AEs with 7 percent, 8 percent, 9 percent, and 4 percent, respectively;
No elevations in liver function tests (ALT/AST) of greater than three times the upper limit of normal, repeated and confirmed were observed.
“These pivotal study results of the bempedoic acid / ezetimibe combination pill are highly compelling. As Lipid Management experts, we know that 35 percent LDL-C lowering could help more than six million ASCVD and/or HeFH patients on maximally tolerated statins achieve LDL-C levels of 70mg/dL or less, an elusive LDL-C target for most patients today. With a reduction in hsCRP as a key marker for CV risk reduction based on CANTOS, our 34 percent hsCRP reduction is truly exceptional,” said Tim M. Mayleben, president and chief executive officer of Esperion. “With the combo pill we are confident physicians will have the treatment option they need to help the more than 12 million Americans with high LDL-C already taking maximally tolerated statin therapy, conveniently and cost-effectively achieve lower LDL-C levels.”
Topline data from Study 2 (1002-047) are now expected in October 2018 (prior guidance end-of-September 2018). NDAs will be submitted during the first quarter of 2019.
FOMX does not have a good technical setup. Price movement has been a little bit too volatile to find a nice entry and exit point. It is probably a good idea to wait for a consolidation first but with the October and early Q4 catalysts, the technical entry is less important.
FMX103 for Papulopustular rosacea. Phase 3 top-line data for FMX103 due early 4Q 2018. Phase 3 clinical trial, FX2017-22, which investigated FMX101 for the treatment of moderate-to-severe acne.
On June 27, 2018, Foamix Pharmaceuticals, a clinical stage specialty pharmaceutical company focused on developing and commercializing proprietary topical foams to address unmet needs in dermatology, announced that it has completed patient enrollment and has dosed the last patient in its two Phase 3 clinical studies (FX2016-11 and FX2016-12) evaluating the safety and efficacy of FMX103, topical minocycline foam 1.5%, for the treatment of rosacea. The two Phase 3 pivotal studies are being run simultaneously, and the Company currently anticipates reporting top-line results early in the fourth quarter of this year.
“Achieving full patient enrollment of these Phase 3 clinical trials is an important developmental milestone for FMX103 and Foamix, as we are now one step closer to providing an effective, convenient, and first-in-class topical treatment for patients with moderate-to-severe papulopustular rosacea,” said David Domzalski, Chief Executive Officer of Foamix. “This is our second announcement this quarter marking full patient enrollment for a Phase 3 clinical program. In early May we announced that the last patient had been enrolled in our third Phase 3 study for FMX101 for the treatment of acne and we look forward to announcing top-line data in the third quarter this year.”
A total of 1522 patients have been enrolled in the rosacea Phase 3 program (751 patients in study FX2016-11 and 771 patients in FX2016-12). Patients who completed participation in either of these studies are given the option to continue into a long-term open-label safety extension to evaluate the safety of intermittent use of FMX103 for up to an additional 9 months (Study FX2016-13). Enrollment in this extension study is also complete, having enrolled 505 patients.
On October 12, 2018, Foamix Pharmaceuticals, a clinical stage specialty pharmaceutical company focused on developing and commercializing proprietary topical therapies to address unmet needs in dermatology, announced that data from its Phase 3 clinical trial, FX2017-22, which investigated FMX101 for the treatment of moderate-to-severe acne, will be presented at the Fall Clinical Dermatology Conference to be held October 18 – 21 at the Wynn Hotel in Las Vegas, Nevada.
The poster, which is entitled “FMX101 4% Topical Minocycline Foam for the Treatment of Moderate-to-Severe Acne Vulgaris: Efficacy and Safety From a Phase 3 Randomized, Double-Blind, Vehicle-Controlled Study” is expected to be presented during several plenary and scientific poster sessions throughout the conference. A copy of the poster will be available on the Foamix corporate website http://foamix.com/, simultaneous with its presentation at the conference.
As the company previously communicated, the Phase 3 study met both co-primary endpoints of (1) absolute change from baseline in inflammatory lesion count at Week 12, and (2) Investigator Global Assessment (“IGA”) treatment success at Week 12, defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline. Results from both co-primary endpoints demonstrated highly statistically significant results for FMX101 vs vehicle, with p-values <0.0001. The favorable safety profile of FMX101 was consistent with that determined from the two prior Phase 3 studies of FMX101 in acne (FX2014-04 and FX2014-05).
I like the setup on GLPG stock. We could be looking at another V bottom bounce and run higher.
GLPG 2451+2222+2737 – FALCON open label, for Cystic fibrosis – homozygous F508del patients. Phase 2 initiation announced April 24, 2018. Top-line data likely due sometime in October 2018.
On April 24, 2018, Galapagos NV announced initiation of its first clinical trial with an investigational triple combination therapy in cystic fibrosis patients.
The aim of the FALCON trial is to evaluate the efficacy, safety, tolerability, and pharmacokinetics of a novel triple combination in up to 24 CF patients. The open label trial is being conducted in multiple centers, initially in the United Kingdom with expansion expected to other European countries.
The FALCON study will comprise two parts. Part one will entail treatment of 8 patients for two weeks with a fixed dose dual combination of potentiator GLPG2451 and C1 corrector GLPG2222 in homozygous F508del patients. This will be followed by two weeks’ treatment with ‘2451, ‘2222, and C2 corrector GLPG2737. Part two will entail treatment for two weeks with a higher dose dual combination of ‘2451 and ‘2222 in separate 8 patient cohorts of homozygous F508del patients and heterozygous F508del patients with a minimal function mutation on the other allele. This will be followed by two weeks’ treatment with ‘2451, ‘2222, and ‘2737. Efficacy will be measured by changes in sweat chloride and percent predicted forced expiratory volume during the first second (ppFEV1%). Topline results from treatment in part one of FALCON are expected to be disclosed Q3 2018.
“Today marks a key milestone in our CF program. Since 2005, it has been our ambition to develop a disease-modifying therapy for CF. Now we are evaluating a first triple combination in CF patients, with the next triple combination coming up rapidly behind it,” said Dr. Piet Wigerinck, CSO of Galapagos. “These steps bring us closer to our goal of offering patients, doctors, and payers more choice in their CF therapies.”
That’s a beautiful candle over candle reversal on the chart.
SEL-212 for Tophaceous gout. Phase 2 five-monthly dose data due at ACR Meeting, October 22, 2018. Pivotal trial to commence 4Q 2018.
Pegylated uricases are therapies for treatment of severe chronic gout, particularly for rapid tophi resolution. However, uricases are limited by induction of anti-drug antibodies (ADA) that can compromise efficacy and safety. SEL-212 is a novel combination product consisting of pegadricase (also known as pegsiticase) co-administered with synthetic vaccine particles encapsulating rapamycin (SVP-R). We report initial data on gout flares from an ongoing Phase 2 study in symptomatic gout patients.
Gout is caused by deposition of monosodium urate (MSU) crystals in joints due to chronic hyperuricemia. Long term treatment focuses on reducing sUA levels, allowing MSU crystals to dissolve. Rapid dissolution of MSU crystals during initial phase of urate lowering therapy (ULT) is associated with an increased frequency of acute gout flares, which can contribute to poor treatment compliance. During ULT initiation, colchicine, NSAIDs or corticosteroids are used for gout flare prophylaxis.
Patients with symptomatic gout (≥1 tophus, gout flare within 6 months or gouty arthropathy) and elevated serum uric acid (sUA) ≥6 mg/dL were treated with fixed doses of pegadricase (0.2 mg/kg or 0.4 mg/kg) alone or in combination with SVP-Rapamycin (0.05 to 0.15 mg/kg). SEL-212 was infused in 28-day cycles x3 doses followed by challenge with pegadricase alone on 28-day cycles x2 doses, or in 28-day cycles x5 combination doses of SVP-Rapamycin and pegadricase. Safety, tolerability, sUA, and ADAs were monitored.
All randomized patients received colchicine (1.2 mg as loading dose, 0.6 mg QD for the remainder of their participation in the trial) as premedication for gout flare prevention. If colchicine was contraindicated, patients received ibuprofen 600 mg TID or equivalent dose of a NSAID. If colchicine and NSAIDs were contraindicated, patients did not receive any premedication.
As of May 21, 2018, demographics of the 140 treated patients were 32 – 75 years old (mean 54.9 years), male 90.7%, and white 67.1%. The mean BMI at baseline was 35.0 kg/m2. 70.0% of patients were obese with mean duration of established or symptomatic gout as 10.8 years.
Flare incidence was 27.1% (months 1-3) and 10.2% (months 4-5), flare frequency was 0.41 flares/patient (months 1-3) and 0.14 flares/patient (months 4-5). Mean duration of the gout flares was 7.28 days, with majority of the gout flares (93.8%) being categorized as mild/moderate, with 6.1% (n=4 cases) noted as severe in intensity. Adjustments to gout flare prevention medication were not required for 43% of the patients. No gout flares resulted in a patient discontinuation or were reported as a serious adverse event.
SEL-212 has been well-tolerated and lowers flares at the initiation of therapy relative to pegylated uricases alone, and the effect persists over the duration of therapy.
Disclosure: I do not hold any position in any stock mentioned in this article.