On August 5, 2020 DermTech, Inc. (NASDAQ: DMTK) ("DermTech" or the "Company"), a leader in precision dermatology enabled by a non-invasive skin genomics platform, reported business and unaudited financial results for the quarter ended June 30, 2020 and also provided a corporate update (Press release, DermTech International, AUG 5, 2020, View Source [SID1234562955]).

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Second Quarter 2020 Financial Results

Billable sample volume of 3,228 was a 12% increase over the 2,875 recorded for the second quarter of 2019 and a 44% sequential decrease compared to the first quarter of 2020.
Assay revenue of $0.6 million was a 128% increase from the second quarter of 2019 and a 19% sequential decrease compared to the first quarter of 2020.
Contract revenue of $0.2 million was a 41% decrease compared to the second quarter of 2019 and a 74% sequential decrease compared to the first quarter of 2019.
Cash and cash equivalents were $61.1 million at the end of the quarter.
"Sales execution for the DermTech Pigmented Lesion Assay ("DermTech PLA") was going very well prior to the COVID-19 pandemic. Billable sample volumes were significantly reduced in April, but have rebounded nicely in recent months and, in July 2020, they recovered to pre-pandemic levels despite the fact that dermatology offices have not fully reopened and continue to be affected by the resurgence of the virus," said John Dobak, M.D., chief executive officer of DermTech. "While early detection of melanoma is critical, and delays can have serious and even deadly consequences, the pandemic caused and could continue to cause a disruption in clinician office visits for assessing suspicious moles. In spite of the challenging macroenvironment, I’m pleased that we have made significant progress on building a foundational commercial infrastructure by growing our sales team, building a digital/telemedicine marketing channel, transitioning to a larger commercial laboratory, and progressing our product pipeline."

Second Quarter 2020 Review and Corporate Update

DermTech is now poised to capture the promising market opportunity in skin cancer, barring any additional significant effects related to the pandemic. We will continue to focus on commercial payer access that will allow us to better monetize our growing billable sample volumes so that our revenues reflect the progress we are making with clinician utilization of the DermTech PLA. We are also looking forward to the introduction of the DermTech PLA plus, our next generation product for enhanced early melanoma detection with better performance, which we believe could catalyze a faster adoption rate. We are pleased with the June and July 2020 recovery and are providing some metrics to better describe recent trends, but note that we do not expect various performance metrics to recover in a linear fashion and are likely to continue to see fluctuations in these metrics as the pandemic’s impact continues and as various cities and offices change COVID-19 related restrictions. These metrics will not necessarily be updated in the future.

The nadir in billable sample volume occurred in April 2020, with volumes down 80% compared to February 2020, following the broad stay-at-home orders. Our billable sample volumes increased steadily in May and June of 2020 and recovered to pre-pandemic levels in July 2020. Billable sample volume for June and July 2020 increased 3% compared to billable sample volume for January and February 2020, demonstrating a strong rebound even without all dermatology practices returning to full operations. Please note that while we are providing additional information regarding July 2020 volume trends due to the pandemic in this update, we do not intend to continue to provide this type of data going forward.
When the COVID-19 pandemic started, we delayed sales force hiring but continued sales force recruiting. As states began to reopen, we restarted our hiring efforts and hired a number of seasoned sales representatives from May through July 2020. We have completed approximately 80% of our sales force expansion efforts for the year and expect to have a sales force of 40-50 personnel in place by the end of 2020. We expect to make some additional hires during 2021.
Our current overall target market includes approximately 13,000 dermatology clinicians. We sized our sales force to reach our current overall target market and prioritized approximately 5,000 clinicians, or our initial target market, who account for a high concentration of the total annual melanoma diagnoses procedures. During the first 6 months of 2020, we penetrated approximately 20% of our initial target market and 8% of our current overall target market with approximately 1,100 unique ordering clinicians.
We had approximately 900 unique ordering clinicians in Q1 2020 and 620 unique ordering clinicians in Q2 2020. Our average quarterly utilization (or average number of tests ordered) per unique ordering clinician was 6.5 billable samples in Q1 2020 and 5.2 billable samples in Q2 2020. In June and July of 2020, we have seen an encouraging trend of increased utilization. We had approximately 780 unique ordering clinicians in January and February 2020, providing approximately 3,880 billable samples. For June and July 2020, we had approximately 680 unique ordering clinicians providing approximately 4,000 billable samples. We believe increased utilization may be a result of several factors including better practice efficiency associated with the use of the DermTech PLA, broader visibility of our test as an important solution for early melanoma detection, particularly during the pandemic, and investments made in a successful digital marketing campaign.
To further illustrate some favorable trends in utilization, clinicians that were high volume users in Q1 2020 are returning to being high volume users as offices reopen. We had an 86% decrease in the number of clinicians ordering 10 or more tests per month in April 2020 compared to February 2020, but in June 2020 we had nearly the same number of clinicians ordering 10 or more tests per month that we had in February 2020. The June 2020 figure represented a 260% increase over June 2019.
We have engaged over 50 commercial payors with approximately 250 million covered lives for coverage and reimbursement determination for the DermTech PLA. This includes national plans, multi-state and individual Blue Cross Blue Shield plans, lab benefit managers and large regional plans. Our engagement has included presenting to these payors our value proposition, peer-reviewed publication library and updates as new studies and programs are available. The COVID-19 pandemic caused delays in payors reviewing new technology for coverage. Many payors have indicated to us that they have had to suspend current processes and had to devote time and redirect resources to respond to the pandemic. There are certain payors that resumed reviewing new technology during the third quarter of 2020, and we expect more payors to resume reviewing new technology prior to the end of 2020.
We have also made progress in addressing our alternative care delivery channel to expand access beyond dermatology, which includes integrated primary care networks, employer-based health care delivery, and remote/telemedicine care models. We have so far engaged in discussions with several organizations that have approximately 50,000 to 80,000 covered lives and will continue to devote resources to develop this new channel.
In April, we launched our DermTech PLA educational webinar series, which will occur periodically each month, and to date is being increasingly attended by practicing clinicians. In addition, our solution has been highlighted in several virtual dermatology educational meetings with over 3,000 attendees as a core solution for managing pigmented lesions remotely.
This April, we announced that clinicians can choose to supervise remote sample collection by patients for the DermTech PLA. If, during a telemedicine visit, a clinician observes that a pigmented lesion is suspicious of melanoma, the clinician can request that we send the DermTech PLA collection kit to the patient’s home for clinician-guided remote collection. We received a modest proportion of our total billable sample volume collected through our telemedicine option in April when stay-at-home orders were largely in effect throughout the country, but that proportion has since decreased as states have begun to reopen and practices have returned to the processes most familiar to them. We believe that the availability of this telemedicine option remains critical for clinicians and patients, especially older patients and patients with underlying health conditions more at risk for complications related to COVID-19, as a telemedicine visit is the only way to assess a pigmented lesion for melanoma remotely. Our telemedicine option eliminates the need for unnecessary office visits as the pandemic continues and various states pause or rollback reopening efforts. We have recently completed a packaging redesign to facilitate the clinician-guided remote sample collection by the patient. Our telemedicine option also enables us to be well-positioned as telemedicine continues to achieve greater acceptance and adoption by clinicians and patients.
Product Development and Pipeline Activities

We received approval from the New York Department of Health for our DermTech PLA plus, and we expect to launch this second-generation product in the fourth quarter of 2020. The DermTech PLA plus includes the original DermTech PLA gene expression analyses combined with TERT mutation analysis and increases the sensitivity of the test without significantly affecting the specificity.
We have continued our development of a branded smartphone app that leverages an existing HIPAA compliant platform to streamline the clinician’s review of suspicious lesions and to enable clinician ordering of DermTech PLA collection kits to be sent to patients’ homes for clinician-guided remote collection. The smartphone app enables secure transmission of patient health information. Regulations for such transmission were eased as part of the pandemic emergency orders but we expect that they may be reinstituted in the future. We also expect our branded smartphone app to be complete and available for beta testing for both iOS and Android platforms in the fourth quarter of 2020.
We completed a proof of concept study for our LuminateTM product and are advancing this product to the validation phase. Our LuminateTM product will assesses ultraviolet ("UV") related mutational burden in normal appearing skin to assess future skin cancer risk and photodamage/skin aging. This study investigated the mutation number and variant allele frequency of UV-associated driver mutations in genes related to basal cell and squamous cell carcinoma. Zero driver mutations were detected in non-sun exposed skin areas, but there was a high frequency of driver-related mutations in normal appearing skin from patients with a history of skin cancer and sun damage. In general, driver-mutation burden correlates with age and history of sun exposure. We believe this product will provide patients and consumers with an option to objectively measure their UV damage related to sun exposure and to seek treatment options and initiate behavior changes to better manage their skin cancer risk and premature photoaging.
We have made significant progress on our CarcinomeTM product, which is in the discovery and translation phase of development. During the quarter we performed whole transcriptome sequencing on approximately 500 samples collected in our non-melanoma skin cancer study. This robust sequencing effort across a broad group of lesions suspicious for non-melanoma skin cancer will allow us to identify gene classifiers capable of detecting basal and squamous cell cancer and differentiating them from non-cancerous lesions that are often unnecessarily surgically biopsied. We expect to identify these classifiers in the third quarter of 2020 and then advance this program to the proof-of-concept stage before moving on to clinical validation.
Clinical and Study Activities

The DermTech PLA was reviewed in the Journal of the American Academy of Dermatology ("JAAD") by leading dermatologists at the New York University School of Medicine as one of four novel molecular technologies with the potential to address current gaps in melanoma management through improved diagnostic accuracy and prognostication. Since its launch in 2016, the DermTech PLA has been used to assess more than 50,000 lesions and remains the first and only non-invasive gene expression test in dermatology, providing objective genomic data to help guide clinical decisions. The article published in JAAD in April 2020 summarized a review of four molecular technologies that analyze skin cells and inherited genetic variations as adjunct tools for melanoma management, providing a comprehensive, evidence-based foundation for clinicians regarding the management of pigmented lesions difficult to assess. The review examined the fundamental principles behind each test, peer-reviewed literature assessing tool performance, and the utility and limitations of each assay.
As we have previously mentioned, results from an Institutional Review Board ("IRB") approved pilot study of seven cases undergoing clinician-guided remote collection were published in the peer-reviewed dermatology journal SKIN in May 2020. In addition, a larger ongoing internal validation effort has enrolled over 250 patients. This small study demonstrated that clinician-guided remote collection is equivalent to in-office clinician collection and that additional samples in an ongoing study further confirm the ability of patients to collect a suitable sample.
TRUST study enrollment has exceeded 80%, and we expect to complete enrollment in the third quarter of 2020. The TRUST study is the first of its kind for the Company to provide repeat clinical assessments and genomic testing on pigmented lesions suspicious for melanoma that were initially tested negative with the DermTech PLA. The Company will continue to enroll this study as patients return for in-office visits, though the timeline to complete the data analysis of the study could be delayed due to COVID-19 complications.
Other Activities

We completed the move of our commercial laboratory into our new space, which allows for greater overall testing capacity and more efficient workflow. We expect our current laboratory to provide sufficient capacity for at least the next few years.
DermTech was added to the Russell 2000 Index effective June 26, 2020. The Russell 2000 Index measures the performance of the small-cap segment of the U.S. equity market. Russell US Indexes are widely used by investment managers and institutional investors as the basis for index funds and as benchmarks for active investment strategies. Russell US Indexes are part of FTSE Russell, a leading global index provider.
Second Quarter 2020 Financial Results

Assay revenue increased 128% to $0.6 million for the three months ended June 30, 2020, compared to $0.3 million for the same period of 2019. Assay revenue for the three months ended June 30, 2020 increased due to higher billable sample volume and revenue recognition of Medicare samples related to the final local coverage determination effective February 10, 2020, compared to the same period of 2019. Contract revenue decreased 41% to $0.2 million for the three months ended June 30, 2020, compared to $0.3 million for the same period of 2019. Contract revenue can be highly variable as it is dependent on the pharmaceutical customers’ clinical trial progress, which can be difficult to forecast due to variability of patient enrollment, drug safety and efficacy and other factors. Total revenues increased 38% to $0.8 million for the three months ended June 30, 2020, compared to $0.6 million for the same period in 2019.

Gross loss for the three months ended June 30, 2020 was 71%, compared to 12% for the same period of 2019. The increase in gross loss was largely driven by higher fixed costs from facilities, equipment and increased headcount to increase testing capacity. In addition, gross loss was negatively affected by the decrease in the Company’s contract revenue and the negative effects from COVID-19 on the Company’s assay revenue during the three months ended June 30, 2020. Assay gross loss for the three months ended June 30, 2020 was 118%.

Sales and marketing expense increased 233% to $3.4 million for the three months ended June 30, 2020, compared to $1.0 million for the same period of 2019. The increase was primarily attributable to sales force expansion to drive the adoption of the DermTech PLA and additional marketing investment to increase awareness of the DermTech PLA as a non-invasive genomic based diagnostic for melanoma.

Research and development expense increased 67% to $0.9 million for the three months ended June 30, 2020, compared to $0.5 million for the same period of 2019. The increase was primarily attributable to higher compensation costs related to expanding the research and development team as well as increased spend on laboratory supplies.

General and administrative expense increased 166% to $4.5 million for the three months ended June 30, 2020, compared to $1.7 million for the same period of 2019. The increase was primarily due to additional public company costs, including higher legal costs related to filings with the Securities and Exchange Commission, higher compensation costs from expanding the general and administrative team, higher insurance costs, and a $1.0 million litigation settlement charge.

Net loss for the three months ended June 30, 2020 was $9.4 million, which included $1.1 million of non-cash stock-based compensation, compared to a net loss of $3.7 million for the same period of 2019, which included $0.3 million of non-cash stock-based compensation.

Cash and cash equivalents totaled $61.1 million as of June 30, 2020.

Update on COVID-19 Impact

During the second quarter of 2020, we continued our broad COVID-19 response to drive education and usage despite reduced patient office visits and in-person sales calls. We are now seeing dermatology offices reopen, although this is highly dependent upon COVID-19 infection rates within various geographic areas. A large portion of our revenue is attributable to sales in states such as Arizona, California, Florida, New York and Texas, and we will be closely monitoring developments there. We expect that reopened dermatology practices may focus initially on essential and time-sensitive dermatology care needs, such as skin cancer assessment, though it is not clear how this will impact our sample volumes.

Our lab remains fully operational and is receiving and analyzing samples as they are collected. In response to the closure of dermatology offices, our sales team has been conducting virtual sales calls and providing client education. We have also introduced a telemedicine option for remote, clinician-guided sample collection by the patient for the DermTech PLA test, which may be important should additional stay-at-home orders or other restrictions occur.

While we cannot predict which states will remain open or will reopen, as noted above, we did see some encouraging data over the last quarter which underscores clinician acceptance of the DermTech PLA and gives us confidence that, in a normalized environment and barring COVID-19 interruptions, we would expect to see strong growth trends.

We have not furloughed or terminated any employees as a result of the COVID-19 related slowdown, nor have we received any federal Paycheck Protection Program ("PPP") loans. Additional increases in headcount and spending associated with higher sample volumes and improving internal capabilities were delayed, but those efforts have resumed as we have started to recover from the pandemic. We expect to continue our originally planned expenditures for research and development and for infrastructure enhancements, including capital equipment.

On August 5, 2020 GeneCentric Therapeutics, Inc. and Erasmus University Medical Center (EUMC) reported that they have entered into a research collaboration to identify RNA-based drug response markers and novel, targeted therapies in the setting of non-muscle invasive bladder cancer (NMIBC) (Press release, GeneCentric Therapeutics, AUG 5, 2020, View Source [SID1234562954]). The research will comprehensively characterize the tumor and immune biology, as well as the tumor microenviroment related to NMIBC, and will apply GeneCentric’s Bladder Cancer Subtype Profiler (BSP), among other novel assays, to predict disease progression and drug response in these patients.

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The collaboration, led at EUMC by Tahlita Zuiverloon, MD, PhD, Principal Investigator at the Erasmus MC Urothelial Cancer Research Group (EUCRG), will involve the retrospective longitudinal, genomic analysis of samples from a sizeable cohort of NMIBC patients who received surgery and adjuvant treatment. "This collaboration will provide a more complete and fundamental understanding of NMIBC drivers of disease progression, innate and active immune system involvement, and factors related to treatment response and failure or drug resistance," said Dr Zuiverloon. "We look forward to the new insights that the application of GeneCentric’s comprehensive molecular profiling platform can provide as we eagerly pursue new therapeutic options for NMIBC patients."

"To date, genomic subtypes for disease progression risk and drug response to NMIBC have not been well characterized," said Dr. Mike Milburn, President and CEO of GeneCentric Therapeutics. "This exciting research collaboration has potential to augment our molecular gene signatures to help define these subtypes and inform clinical decision making and drug development. There is a significant clinical need and opportunity to improve outcomes, as treatment of NMIBC is evolving with the emergence of novel targeted therapies, potentially including FGFR inhibitors, in addition to the current standard of care."

On August 5, 2020 Pfizer Inc. (NYSE:PFE) reported that the Phase 3 CROWN study of LORBRENA (lorlatinib) in people with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) met its primary endpoint by demonstrating significantly improved progression-free survival (PFS), as compared to XALKORI (crizotinib)(Press release, Pfizer, AUG 5, 2020, View Source [SID1234562953]) . The results were reviewed by an independent Data Monitoring Committee (DMC) at a planned interim analysis. The safety profile for lorlatinib and crizotinib were consistent with what has been previously seen in clinical trials. The results from CROWN will be submitted for presentation at an upcoming medical congress.

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"Almost a decade ago, we pioneered the first biomarker-driven medicine for ALK-positive non-small cell lung cancer, which transformed treatment of this disease," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "These top-line results of the CROWN study reinforce the significant benefit of LORBRENA demonstrated in later-line settings, and we are excited to share these data soon with physicians and other healthcare providers, as well as engage with global regulatory authorities to potentially provide people with previously untreated metastatic non-small cell lung cancer this third-generation ALK-inhibitor."

In 2018, the U.S. Food and Drug Administration (FDA) approved LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. This indication is approved under accelerated approval based on tumor response rate and duration of response. CROWN is the confirmatory study for the conversion to full approval. Based on the positive outcome of the CROWN trial, we intend to share the results with the FDA and other health authorities to support conversion to full approval and to seek approval for an indication that includes previously untreated ALK-positive metastatic NSCLC.

CROWN is a Phase 3, randomized, open-label, parallel 2-arm study in which 296 people with previously untreated advanced ALK-positive NSCLC were randomized 1:1 to receive LORBRENA monotherapy or XALKORI monotherapy. The primary endpoint of the CROWN trial is PFS based on blinded independent central review (BICR). Secondary endpoints include overall survival, PFS based on investigator’s assessment, objective response (OR) based on BICR and on investigator’s assessment; intracranial OR (IC-OR), IC time to progression, duration of response (DR), IC-DR, time to tumor response (TTR), IC-TTR (all by BICR); PFS2 based on investigator’s assessment, and safety.

Lung cancer is the number one cause of cancer-related death around the world.1 NSCLC accounts for approximately 80-85% of lung cancers,2 with ALK-positive tumors occurring in about three to five percent of NSCLC cases.3 Prior to the availability of targeted therapy and immunotherapy, the five-year survival rate for patients with advanced NSCLC was just five percent.4

About LORBRENA (lorlatinib)

LORBRENA is a tyrosine kinase inhibitor (TKI) that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORBRENA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORBRENA is approved in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:

crizotinib and at least one other ALK inhibitor for metastatic disease; or
alectinib as the first ALK inhibitor therapy for metastatic disease; or
ceritinib as the first ALK inhibitor therapy for metastatic disease.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The full prescribing information for LORBRENA can be found here.

IMPORTANT LORBRENA (lorlatinib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. ALT or AST elevations occurred within 3 days and returned to within normal limits after a median of 15 days (7 to 34 days); median time to recovery in subjects with Grade 3 or 4 or Grade 2 ALT or AST elevations was 18 days and 7 days, respectively. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA. Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur; overall, CNS effects occurred in 54% of 332 patients receiving LORBRENA. These included seizures (3%, sometimes in conjunction with other neurologic findings), hallucinations (7%; 0.6% severe [Grade 3 or 4]), and changes in cognitive function (29%; 2.1% severe), mood (including suicidal ideation) (24%; 1.8% severe), speech (14%; 0.3% severe), mental status (2.1%; 1.8% severe), and sleep (10%). Median time to first onset of any CNS effect was 1.2 months (1 day to 1.7 years). Overall, 1.5% and 9% of patients required permanent or temporary discontinuation of LORBRENA, respectively, for a CNS effect; 8% required dose reduction. Withhold and resume at same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA. Median time to onset was 15 days for both hypercholesterolemia and hypertriglyceridemia. Approximately 7% and 3% of patients required temporary discontinuation or dose reduction of LORBRENA, respectively, for elevations in cholesterol and in triglycerides. Eighty percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 21 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 295 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1% experienced AV block and 0.3% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. One patient (0.3%) discontinued LORBRENA for ILD/pneumonitis. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis. Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The most common (≥20%) adverse reactions were (all Grades; Grade 3 or 4): edema (57%; 3.1%), peripheral neuropathy (47%; 2.7%), cognitive effects (27%; 2.0%), dyspnea (27%; 5.4%), fatigue (26%; 0.3%), weight gain (24%; 4.4%), arthralgia (23%; 0.7%), mood effects (23%; 1.7%), and diarrhea (22%; 0.7%); the most common (≥20%) laboratory abnormalities were (all Grades; Grade 3 or 4): hypercholesterolemia (96%; 18%), hypertriglyceridemia (90%; 18%), anemia (52%; 4.8%), hyperglycemia (52%; 5%), increased AST (37%; 2.1%), hypoalbuminemia (33%; 1.0%), increased ALT (28%; 2.1%), increased lipase (24%; 10%), and increased alkaline phosphatase (24%; 1.0%).

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers and strong CYP3A inhibitors. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the LORBRENA dose as recommended. Avoid concomitant use of LORBRENA with CYP3A substrates and P-gp substrates, which may reduce the efficacy of these substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of LORBRENA has not been established for patients with severe renal impairment.

About XALKORI (crizotinib)

XALKORI is a TKI indicated for the treatment of patients with metastatic NSCLC whose tumors are ALK- or ROS1-positive as detected by an FDA-approved test. XALKORI has received approval for patients with ALK-positive NSCLC in more than 90 countries including Australia, Canada, China, Japan, South Korea and the European Union. XALKORI is also approved for ROS1-positive NSCLC in more than 60 countries.

The full prescribing information for XALKORI can be found here.

IMPORTANT XALKORI (crizotinib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of patients treated with XALKORI across clinical trials (n=1719). Increased transaminases generally occurred within the first 2 months. Monitor liver function tests, including ALT, AST, and total bilirubin, every 2 weeks during the first 2 months of treatment, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. Permanently discontinue for ALT/AST elevation >3 times ULN with concurrent total bilirubin elevation >1.5 times ULN (in the absence of cholestasis or hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI as indicated.

Interstitial Lung Disease/Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9% of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4, and 0.5% had fatal ILD. ILD generally occurred within 3 months after initiation of treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes and permanently discontinue XALKORI in patients with drug-related ILD/pneumonitis.

QT Interval Prolongation: QTc prolongation can occur. Across clinical trials (n=1616), 2.1% of patients had QTcF (corrected QT by the Fridericia method) ≥500 ms and 5% of 1582 patients had an increase from baseline QTcF ≥60 ms by automated machine-read evaluation of ECGs. Avoid use in patients with congenital long QT syndrome. Monitor ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia. Withhold XALKORI in patients who develop QTc >500 ms on at least 2 separate ECGs until recovery to a QTc ≤480 ms, then resume at next lower dosage.

Bradycardia: Symptomatic bradycardia can occur. Across clinical trials, bradycardia occurred in 13% of patients treated with XALKORI (n=1719). Avoid use in combination with other medications known to cause bradycardia. Monitor heart rate and blood pressure regularly. If bradycardia occurs, re-evaluate for the use of concomitant medications known to cause bradycardia. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring.

Severe Visual Loss: Across clinical trials, the incidence of Grade 4 visual field defect with vision loss was 0.2% of 1719 patients. Discontinue XALKORI in patients with new onset of severe visual loss (best corrected vision less than 20/200 in one or both eyes). Perform an ophthalmological evaluation. There is insufficient information to characterize the risks of resumption of XALKORI in patients with a severe visual loss; a decision to resume should consider the potential benefits to the patient.

Vision Disorders: Most commonly visual impairment, photopsia, blurred vision or vitreous floaters, occurred in 63% of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had Grade 4 visual impairment. The majority of patients on the XALKORI arms in Studies 1 and 2 (>50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact on daily activities.

Embryo-Fetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 45 days (females) or 90 days (males) respectively, following the final dose of XALKORI.

ROS1-positive Metastatic NSCLC: Safety was evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study, and was generally consistent with the safety profile of XALKORI evaluated in patients with ALK-positive metastatic NSCLC. Vision disorders occurred in 92% of patients in the ROS1 study; 90% of patients had Grade 1 vision disorders and 2% had Grade 2.

Adverse Reactions: Safety was evaluated in a phase 3 study in previously untreated patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169). Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% of patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis. Common adverse reactions (all grades) occurring in ≥25% and more commonly (≥5%) in patients treated with XALKORI vs chemotherapy were vision disorder (71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting (46% vs 36%), constipation (43% vs 30%), upper respiratory infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain (26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher incidence with XALKORI vs chemotherapy were QT prolongation (2% vs 0%), esophagitis (2% vs 0%), and constipation (2% vs 0%). In patients treated with XALKORI vs chemotherapy, the following occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea (56%), decreased appetite (30%), fatigue (29%), and neuropathy (21%) also occurred in patients taking XALKORI.

Drug Interactions: Use caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Avoid concomitant use of CYP3A substrates where minimal concentration changes may lead to serious adverse reactions. If concomitant use of XALKORI is unavoidable, decrease the CYP3A substrate dosage in accordance with approved product labeling.

Lactation: Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with XALKORI and for 45 days after the final dose.

Hepatic Impairment: Crizotinib concentrations increased in patients with pre-existing moderate (any AST and total bilirubin >1.5x ULN and ≤3x ULN) or severe (any AST and total bilirubin >3x ULN) hepatic impairment. Reduce XALKORI dosage in patients with moderate or severe hepatic impairment. The recommended dose of XALKORI in patients with pre-existing moderate hepatic impairment is 200 mg orally twice daily or with pre-existing severe hepatic impairment is 250 mg orally once daily.

Renal Impairment: Decreases in estimated glomerular filtration rate occurred in patients treated with XALKORI. Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis.

On August 5, 2020 Teva Pharmaceutical Industries Ltd. (NYSE: and TASE: TEVA) and biopharmaceutical company Alvotech reported that they have entered into an exclusive strategic partnership for the commercialization in the U.S. of five biosimilar product candidates (Press release, Teva, AUG 5, 2020, View Source [SID1234562952]). This strategic partnership combines Teva’s long-standing commercial presence and extensive infrastructure in the U.S. market with Alvotech’s scientific experience and state-of-the-art biologics manufacturing. The initial pipeline contains biosimilar candidates addressing multiple therapeutic areas.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Robert Wessman, Alvotech’s founder and Chairman said, "We are very proud to announce our strategic alliance with Teva – a leading global pharmaceutical company, to accelerate the introduction and adoption of new biosimilar medicines for patients in the U.S. market. This is not only a big moment for the biosimilar industry but also a very special moment for Alvotech, as we continue to join forces with leading global and regional partners around the world."

"This commercial partnership with Alvotech will enable Teva to lend its technical expertise in working with the FDA to bring products to the U.S. market while broadening its growing biosimilar portfolio and continuing to leverage its unique cross-functional expertise across both specialty and generic medicines," said Brendan O’Grady, Executive Vice President and Head of North America Commercial at Teva. "This collaboration is another step in our unwavering commitment to develop and enable access to quality medications to help improve the lives of patients."

Under this partnership agreement, Alvotech will be responsible for the development, registration and supply of the biosimilars, while Teva will be exclusively commercializing the products in the U.S. The originator products of these five candidates currently generate around $35 billion in U.S. sales. The agreement includes an upfront payment, with subsequent milestone payments over the next several years. Teva and Alvotech will share profit from the commercialization of the biosimilars. All other financial terms and product details remain confidential.

On August 5, 2020 Exicure, Inc. (NASDAQ:XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported that David Giljohann, CEO, will present a Fireside Chat at the BTIG Virtual Biotechnology Conference 2020 on Monday, August 10, 2020 (Press release, Exicure, AUG 5, 2020, View Source [SID1234562951]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Date: Monday, August 10, 2020
Time: 1:30 PM Eastern Time
Location: Virtual Webcast

The presentation will be available for live streaming via View Source and will also be available on BTIG’s conference portal.

Replays of the webcast will be available on Exicure’s website for 30 days following the webcast.