On February 14, 2018 Alkermes plc (Nasdaq: ALKS) today reported financial results for the twelve months ended Dec. 31, 2017 and provided financial expectations for 2018 (Press release, Alkermes, FEB 14, 2018, View Source [SID1234523962]).

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Quarter Ended Dec. 31, 2017 Financial Highlights

•Total revenues for the quarter were $275.4 million. This compared to $213.5 million for the same period in the prior year, representing an increase of 29%.

•Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $9.8 million, or a basic and diluted GAAP loss per share of $0.06. This compared to GAAP net loss of $21.1 million, or a basic and diluted GAAP loss per share of $0.14 for the same period in the prior year.

•Non-GAAP net income was $50.3 million, or a non-GAAP basic earnings per share of $0.33 and non-GAAP diluted earnings per share of $0.31, for the quarter. This compared to non-GAAP net income of $23.3 million, or a non-GAAP basic and diluted earnings per share of $0.15, for the same period in the prior year.

Quarter Ended Dec. 31, 2017 Financial Results

Revenues

•Net sales of VIVITROL were $75.6 million, compared to $62.1 million for the same period in the prior year, representing an increase of 22%.

•Net sales of ARISTADA were $28.3 million, compared to $17.3 million for the same period in the prior year, representing an increase of 64%.

•Manufacturing and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA were $78.2 million, compared to $74.0 million for the same period in the prior year.

•Manufacturing and royalty revenues from AMPYRA/FAMPYRA1 were $38.1 million, compared to $32.3 million for the same period in the prior year.

•Revenues from the collaboration with Biogen for BIIB098 (formerly ALKS 8700) included $28.0 million of license revenue and $2.3 million of R&D reimbursement.

Costs and Expenses

•Operating expenses were $269.5 million, compared to $237.1 million for the same period in the prior year.

•Income tax provision of $20.6 million included a $21.5 million tax charge related to the reduction in the value of our deferred tax assets due to the enactment of the Tax Cuts and Jobs Act of 2017. This compared to an income tax benefit of $3.2 million for the same period in the prior year.

Calendar Year 2017 Financial Highlights

•Total revenues increased 21% to $903.4 million in 2017, which included VIVITROL net sales of $269.3 million and ARISTADA net sales of $93.5 million. This compared to total revenues of $745.7 million for 2016, which included VIVITROL net sales of $209.0 million and ARISTADA net sales of $47.2 million. Please see the tables at the end of this press release for a detailed breakdown of the revenues from our key commercial products.

•GAAP net loss was $157.9 million, or a basic and diluted GAAP loss per share of $1.03, for 2017. This compared to a GAAP net loss of $208.4 million, or a basic and diluted GAAP loss per share of $1.38, for 2016.

•Non-GAAP net income was $27.8 million, or a non-GAAP basic earnings per share of $0.18 and non-GAAP diluted earnings per share of $0.17, for 2017. This compared to non-GAAP net loss of $10.3 million, or a non-GAAP basic and diluted loss per share of $0.07, for 2016.

•At Dec. 31, 2017, Alkermes recorded cash, cash equivalents and total investments of $590.7 million, compared to $619.2 million at Dec. 31, 2016. At Dec. 31, 2017, the company’s total debt outstanding was $281.4 million, compared to $283.7 million at Dec. 31, 2016.

"Our financial results in 2017 were driven by the strong year-over-year growth of our proprietary products, VIVITROL and ARISTADA, our base royalty and manufacturing business and our strategic alliance with Biogen for BIIB098. We exited the year well positioned to execute on our key strategic initiatives in 2018," commented James Frates, Chief Financial Officer of Alkermes. "Looking ahead, 2018 will be a transformative year for Alkermes. Our financial expectations for 2018 reflect important investments that will drive future value as we advance our late-stage pipeline and prepare for the anticipated launch of ALKS 5461, with the planned expansion of our commercial organization midyear. We also expect solid growth for VIVITROL and ARISTADA, and remain committed to driving awareness and advancing the treatment paradigm for these important medicines."

Recent Events:

•ALKS 5461: In January 2018, Alkermes submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ALKS 5461 for the adjunctive treatment of major depressive disorder (MDD). ALKS 5461 was granted Fast Track status by the FDA in October 2013 for the adjunctive treatment of MDD in patients with an inadequate response to standard antidepressant therapies.

•BIIB098: Biogen and Alkermes announced a license and collaboration agreement for the development and commercialization of BIIB098 for the treatment of relapsing forms of Multiple Sclerosis (MS). Under the terms of the agreement, Alkermes granted Biogen an exclusive, worldwide license to develop and commercialize BIIB098 and Biogen will pay Alkermes a mid-teens royalty on worldwide net sales of BIIB098. Biogen is responsible for all development and commercialization expenses, effective Jan. 1, 2018. Alkermes may also receive milestone payments for BIIB098 with a maximum aggregate value of $200 million upon certain clinical and regulatory achievements.

•ARISTADA: A NDA was filed with the FDA for Aripiprazole Lauroxil NanoCrystal Dispersion (ALNCD), a novel, investigational product designed for initiation onto ARISTADA. A target action date of June 30, 2018 was assigned to the ALNCD NDA under the Prescription Drug User Fee Act (PDUFA).

•VIVITROL: Results from the National Institute on Drug Abuse (NIDA)-funded X:BOT study, comparing extended-release naltrexone (VIVITROL) and buprenorphine-naloxone, were published in The Lancet. Data from the study demonstrated that, once treatment was initiated, both medications were equally safe and effective in preventing relapse to opioid dependence.

•ALKS 4230: Preclinical data on ALKS 4230 was presented at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The data showed that treatment with ALKS 4230 significantly delayed tumor growth and led to accumulation of tumor-killing T cells in the tumor microenvironment in individualized and humanized melanoma xenograft models of tumor immunology.

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"We are making significant progress in advancing our pipeline of late-stage CNS development candidates, highlighted by the recent submission of the ALKS 5461 NDA, the recently announced license and collaboration agreement with Biogen to develop and commercialize BIIB098, and as we near completion of enrollment in the six-month pivotal weight study for ALKS 3831," said Richard Pops, Chief Executive Officer of Alkermes. "Alkermes has worked for many years toward this moment. With a diversified CNS business and significant news flow expected across our pipeline of development candidates in 2018, we are focused on executing on our business strategy to bring these important potential new medicines to patients and creating value for our shareholders."

2018 Expected Milestones

The following outlines the company’s expected milestones for 2018. The following statements are forward-looking, and actual results may differ materially. Please see "Note Regarding Forward-Looking Statements" at the end of this press release for risks that could cause results to differ materially from these forward-looking statements.

•VIVITROL

oPublication and presentation of detoxification protocols for induction onto VIVITROL from recent clinical trials (H1)

•ARISTADA

oALNCD for initiation onto ARISTADA PDUFA target action date (June 30, 2018)

•ALKS 5461

oAssignment of PDUFA target action date, following NDA acceptance (Q2)

oPotential Advisory Committee meeting and FDA action (H2)

•ALKS 3831

oENLIGHTEN-2 six-month weight study enrollment completion (Q1)

oPhase 1 human metabolic study data presentation (H1)

oENLIGHTEN-2 topline results (Fall)

•BIIB098 (formerly ALKS 8700)

oPotential receipt of $50 million payment following initial data from EVOLVE-MS-2 gastrointestinal head-to-head study (mid-2018)

oPlanned NDA submission for treatment of MS (H2)

•ALKS 4230

oDose escalation data and dose expansion initiation (H2)

oPlanned submission of Investigational New Drug (IND) application for subcutaneous dosing phase 1 study (H2)

Financial Expectations for 2018

The following outlines the company’s financial expectations for 2018, which include investments in commercial infrastructure in preparation for the expected launch of ALKS 5461 and in the company’s pipeline of late-stage development candidates. The following statements are forward-looking, and actual results may differ materially. Please see "Note Regarding Forward-Looking Statements" at the end of this press release for risks that could cause results to differ materially from these forward-looking statements.

•Revenues: The company expects total revenues to range from $975 million to $1.025 billion, driven by continuing growth of VIVITROL and ARISTADA. Included in this total revenue expectation, Alkermes expects VIVITROL net sales to range from $300 million to $330 million, and ARISTADA net sales to range from $140 million to $160 million.

•Cost of Goods Manufactured and Sold: The company expects cost of goods manufactured and sold to range from $180 million to $190 million.

•Research and Development (R&D) Expenses: The company expects R&D expenses to range from $415 million to $445 million.

•Selling, General and Administrative (SG&A) Expenses: The company expects SG&A expenses to range from $555 million to $585 million. This increase reflects important planned investment in the

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expansion of our commercial organization in preparation for the anticipated launch of ALKS 5461.

•Amortization of Intangible Assets: The company expects amortization of intangibles to be approximately $65 million.

•Net Interest Expense: The company expects net interest expense to be approximately $10 million.

•Income Tax Expense: The company expects income tax expense of up to $10 million.

•GAAP Net Loss: The company expects GAAP net loss to range from $250 million to $280 million, or a basic and diluted loss per share of $1.61 to $1.81, based on a weighted average basic and diluted share count of approximately 155 million shares outstanding.

•Non-GAAP Net Loss: The company expects non-GAAP net loss to range from $5 million to $35 million, or a non-GAAP basic and diluted loss per share of $0.03 to $0.23, based on a weighted average basic and diluted share count of approximately 155 million shares outstanding.

•Capital Expenditures: The company expects capital expenditures to range from $80 million to $90 million.

Conference Call

Alkermes will host a conference call at 8:30 a.m. ET (1:30 p.m. GMT) on Wednesday, Feb. 14, 2018, to discuss these financial results and provide an update on the company. The conference call may be accessed by visiting Alkermes’ website or by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988. In addition, a replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. GMT) on Wednesday, Feb. 14, 2018, through 5:00 p.m. ET (10:00 p.m. GMT) on Wednesday, Feb. 21, 2018, and may be accessed by visiting Alkermes’ website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.

On February 14, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported its financial results for the second quarter ended December 31, 2017 (Press release, DelMar Pharmaceuticals, FEB 14, 2018, View Source [SID1234523988]). DelMar executive management will host a business update conference call for investors, analysts and other interested parties on Tuesday, February 20, 2018 at 4:30 p.m. Eastern Standard Time.

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"This quarter has been an exciting period for DelMar. Our priority is to leverage VAL-083’s unique mechanism of action to efficiently advance it into the most promising indications, including MGMT-unmethylated glioblastoma and platinum-resistant ovarian cancer. We now have a revised VAL-083 development strategy that is focused on MGMT methylation status in glioblastoma, which has become routine in clinical practice as a biomarker which correlates with resistance to the standard-of-care chemotherapy with temozolomide (Temodar "TMZ"), and patient outcomes. We believe using this biomarker will allow us to optimize patient selection for treatment with our lead drug candidate, VAL-083, thereby streamlining development and enhancing opportunities for success in our clinical development programs," commented Saiid Zarrabian, Interim President and Chief Executive Officer.

KEY DEVELOPMENTS AND UPDATED STRATEGIC PLAN

● Evaluation of MGMT promoter methylation status has increasingly become common practice in the diagnostic assessment of glioblastoma multiforme (GBM). DelMar believes that this provides it with an enhanced ability to leverage MGMT methylation as a biomarker to optimize patient selection for DelMar’s novel DNA-targeting agent in the treatment of GBM.

● The National Comprehensive Cancer Network (NCCN), provided updated guidelines for the standard treatment of GBM based on MGMT methylation status. DelMar believes these recently published guidelines may allow the Company to capitalize on VAL-083’s unique mechanism of action and activity in the estimated 60 percent of GBM patients whose tumors are MGMT-unmethylated.

● The U.S. Food and Drug Administration (FDA) allowed a second Investigational New Drug Application (IND) to enable DelMar to study its lead drug candidate, VAL-083, as a potential treatment for ovarian cancer.

● In November 2017, at the annual meeting of the Society for NeuroOncology (SNO), DelMar presented a positive interim update from its ongoing open label Phase 2 clinical trial in patients with MGMT-unmethylated recurrent GBM (rGBM) whose tumors have recurred following treatment with temozolomide (Avastin naïve). This study, which was initiated in February 2017, is being conducted at the University of Texas MD Anderson Cancer Center.

● In December 2017, the FDA fully approved Avastin (bevacizumab) which may impact our ability to recruit suitable patients for our STAR-3 Phase 3 clinical trial.

● In December 2017, the FDA granted Fast Track designation for VAL-083, in recurrent glioblastoma.

● Based on the above developments, and other factors as stated in DelMar’s Quarterly Report on Form 10-Q for the quarter ended December 31, 2017 (10-Q) filed with the Securities and Exchange Commission (SEC) on February 14, 2018, DelMar has decided to put the STAR-3 program on hold for up to 12 months and will suspend further site or patient enrollment. This will allow DelMar to fully evaluate the possible impact of Avastin’s recent approval by the FDA on patient enrollment for this study, and possible protocol amendments, non-dilutive financing sources, as well as to increase focus on the MGMT-unmethylated clinical studies currently underway as further described in the SEC filings. During this interim evaluation period, DelMar will continue to provide treatment to patients already enrolled in the STAR-3 trial, and consider, on a case-by-case basis, and subject to required institutional and regulatory approvals, providing VAL-083 to patients in accordance with our expanded access policy

● Based on this updated strategy, DelMar believes it has cash available into the second quarter of calendar 2019.

For further details on the Company’s operating and financial results, as well as more detail about its updated strategy, refer to DelMar’s 10-Q filed with the SEC on February 14, 2018, View Source

CONFERENCE CALL DETAILS

DelMar plans to host a conference call to discuss its financial results for the quarter ended December 31, 2017 and provide a corporate update on Tuesday, February 20, 2018, at 4:30 p.m. Eastern Time. For both "listen-only" participants and those who wish to take part in the question and answer portion of the call, the telephone Dial-in Number is 1 888 632 3384 (toll free) with Conference ID DELMAR.

A replay of the conference call will be available on the IR Calendar of the Investors section of the Company’s website at www.delmarpharma.com and will be archived for 30 days.

SUMMARY OF FINANCIAL RESULTS FOR THE PERIOD ENDED DECEMBER 31, 2017

At December 31, 2017, the Company had cash and clinical trial deposits on hand of approximately $12.0 million (unaudited).

For the three months ended December 31, 2017, the Company reported a net loss of $3,161,598 or $0.14 per share, compared to a net loss of $1,321,973, or $0.13 per share, for the three months ended December 31, 2016. For the six months ended December 31, 2017, the Company reported a net loss of $5,828,004 or $0.31 per share, compared to a net loss of $3,612,312, or $0.36 per share, for the six months ended December 31, 2016.

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The following represents selected financial information as of December 31, 2017. The Company’s financial information has been prepared in accordance with U.S. GAAP and this selected information should be read in conjunction with DelMar’s consolidated financial statements and management’s discussion and analysis ("MD&A"), as filed.

DelMar’s financial statements as filed with the U.S. Securities Exchange Commission can be viewed on the company’s website at: View Source

Selected Balance Sheet Data

December 31,
2017
$

June 30,
2017
$

Cash 11,021,568 6,586,014
Working capital 9,959,948 6,566,371
Total assets 12,216,116 7,911,021
Derivative liability 5,549 61,228
Total stockholders’ equity 9,983,574 6,578,524

Selected Statement of Operations Data

For the three months ended:

December 31, December 31,
2017 2016
$ $

Research and development 2,141,945 1,120,910
General and administrative 1,011,879 571,286
Change in fair value of stock option and derivative liabilities 889 (361,668 )
Foreign exchange loss (gain) 7,120 (8,495 )
Interest income (235 ) (60 )
Net and comprehensive loss for the period 3,161,598 1,321,973
Series B Preferred stock dividend 54,066 159,756
Net and comprehensive loss available to common stockholders 3,215,664 1,481,729
Basic weighted average number of shares outstanding 22,559,234 11,424,485
Basic and fully diluted loss per share 0.14 0.13

Excluding the impact of non-cash expense, research and development expenses increased to $2,015,570 during the current quarter compared to $1,186,637 for the same period in the prior year. The increase was largely attributable to an increase in clinical development costs related to the three clinical studies ongoing for VAL-083, as well as personnel, and preclinical research costs. Excluding the impact of non-cash expenses, general and administrative expenses increased in the quarter ended December 31, 2017 to $909,747 from $580,761 for the quarter ended December 31, 2016.

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For the six months ended:

December 31, December 31,
2017 2016
$ $

Research and development 4,076,588 1,853,639
General and administrative 1,756,500 1,887,925
Change in fair value of stock option and derivative liabilities (55,679 ) (135,980 )
Foreign exchange loss 50,986 6,829
Interest income (391 ) (101 )
Net and comprehensive loss for the period 5,828,004 3,612,312
Series B Preferred stock dividend 95,732 467,054
Net and comprehensive loss available to common stockholders 5,923,736 4,079,366
Basic weighted average number of shares outstanding 18,882,259 11,363,237
Basic and fully diluted loss per share 0.31 0.36

Excluding the impact of non-cash expense, research and development expenses increased to $3,955,187 during the six months ended December 31, 2017 compared to $1,863,529 for the same period in the prior year. The increase was largely attributable to VAL-083 clinical development and manufacturing costs related to the Company’s STAR-3 refractory-GBM clinical trial and two Phase 2 clinical trials in MGMT-unmethylated GBM.

Excluding the impact of non-cash expenses, general and administrative expenses increased in the current six months to $1,586,005 compared to $1,307,175 for the six months ended December 31, 2016.

We believe, based on our current estimates, that we will be able to fund our operations into the second quarter of calendar year 2019.

On February 14, 2018 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported that its abstract highlighting interim results of its Phase 2 study on HS-110 (viagenpumatucel-L) and nivolumab (Opdivo) combination therapy in the treatment of advanced non-small cell lung cancer (NSCLC), has been accepted as a scientific poster presentation during the 2018 Keystone Symposia Conference XI: Immunological Memory: Innate, Adaptive and Beyond, February 25 – March 1, 2018 in Austin (Press release, Heat Biologics, FEB 14, 2018, View Source [SID1234523971]).

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The poster presentation details are as follows:

Title: "Correlation of Adaptive Immune Response with Clinical Response after Treatment with Viagenpumatucel-L and Nivolumab in Previously Treated Non-Small Cell Lung Cancer (NSCLC) Patients"
Session Date/Time: February 27, 2018, 7:30 p.m. – 10 p.m. CT
Authors: Lori McDermott, MSc; Vamsidhar Velcheti, MD; Roger B. Cohen, MD; Jeff Hutchins, PhD; Daniel Morgensztern, MD
In addition, Heat will be hosting an analyst and investor event in New York City on February 28, 2018, at 8 a.m. ET, to discuss these results. Event details and webcast information to be provided prior to the event.

On February 14, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has approved ERLEADA (apalutamide), a next-generation androgen receptor inhibitor,1 for the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) (Press release, Johnson & Johnson, FEB 14, 2018, View Source [SID1234523973]). ERLEADA is the first FDA-approved treatment for these patients. Today’s approval follows an FDA Priority Review designation based upon data from the Phase 3 SPARTAN study, which demonstrated a 72 percent reduction in risk of distant metastasis or death, and an increase in median metastasis-free survival (MFS) by more than two years (difference of 24.31 months) in patients with NM-CRPC.

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"The need to delay metastasis is critical to the treatment of prostate cancer. Nearly 90 percent of patients with castration-resistant prostate cancer will eventually develop bone metastases, at which point the prognosis sharply worsens," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are excited about what this approval means for patients living with prostate cancer, and that physicians now have an important and much-needed treatment option that has been shown to delay the progression of castration-resistant prostate cancer."

ERLEADA received FDA approval based on the Phase 3 data from the SPARTAN clinical trial, which assessed the efficacy and safety of ERLEADA versus placebo in patients with NM-CRPC who had a rapidly rising PSA while receiving continuous androgen deprivation therapy.2 The study was recently presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) on Thursday, February 8, 2018 in San Francisco and published in The New England Journal of Medicine.2,3

"The SPARTAN trial results demonstrated impressive clinical benefits in patients with non-metastatic castration-resistant prostate cancer," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center, Professor of Medicine at Harvard Medical School, and co-principal investigator of the SPARTAN study. "As an oncologist and clinical investigator, I know how devastating it can be for patients and their families to hear that the cancer has spread. With this approval, doctors now have the chance to offer hope for delaying metastases in patients with castration-resistant prostate cancer."

"As the impact of prostate cancer continues to grow, we are reminded every day of the critical need for therapeutic options that offer patients with prostate cancer more time with their loved ones," Mark Scholz, M.D., Executive Director of the Prostate Cancer Research Institute. "Today’s approval is significant, as it means that patients with non-metastatic castration-resistant prostate cancer now have a treatment option that offers renewed hope."

SPARTAN, a Phase 3, randomized, double-blind, placebo-controlled, multi-center study, enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer.4 Patients were randomized 2:1 to receive either ERLEADA orally at a dose of 240 mg once daily (n=806), or placebo once daily (n=401).4 All patients in the SPARTAN trial received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy.4

ERLEADA decreased the risk of distant metastasis or death by 72 percent compared to placebo (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001).4 The median MFS was 40.51 months for ERLEADA compared to 16.20 months for placebo, prolonging MFS by more than two years (difference of 24.31 months).4 MFS benefit was consistently seen across patient subgroups including prostate specific antigen doubling time (PSADT) (≤6 months or >6 months), use of a prior bone-sparing agent (yes or no), and locoregional disease (N0 or N1).4

The major efficacy outcome was supported by statistically significant improvements for the following secondary endpoints: time to metastasis (TTM), progression-free survival (PFS) and time to symptomatic progression.4 The median TTM was 40.51 months for ERLEADA compared to 16.59 months for placebo (HR=0.27; 95% CI, 0.22-0.34; P<0.0001) and the median PFS was 40.51 months compared to 14.72 months for placebo (HR=0.29; 95% CI, 0.24-0.36; P<0.0001).4 Overall survival data were not mature at the time of final MFS analysis (24% of the required number of events).4

Warnings and Precautions include seizure, falls and fractures.4 In the SPARTAN trial, the most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.4

About Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (NM-CRPC) refers to a disease state when the cancer no longer responds to medical or surgical treatments that lower testosterone, but has not yet been discovered in other parts of the body using a total body bone scan or CT scan.5 Features include: lack of detectable metastatic disease;5 rapidly rising prostate-specific antigen while on androgen deprivation therapy (ADT) and serum testosterone level below 50 ng/dL.6,7 Ninety percent of patients with CRPC will eventually develop bone metastases, which can lead to pain, fractures and spinal cord compression.8 The relative 5-year survival rate for patients with distant stage prostate cancer is 30 percent.9 It is critical to delay the onset of metastasis in patients with NM-CRPC.

About ERLEADA
ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.4

ERLEADA is an AR inhibitor that binds directly to the ligand-binding domain of the AR. ERLEADA inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.4 A major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of ERLEADA in an in vitro transcriptional reporter assay.4 ERLEADA administration caused decreased tumor cell proliferation and increased apoptosis leading to decreased tumor volume in mouse xenograft models of prostate cancer.4

Full prescribing information will be available soon at www.ERLEADA.com.

Important Safety Information4

CONTRAINDICATIONS

Pregnancy – ERLEADA can cause fetal harm and potential loss of pregnancy.

WARNINGS AND PRECAUTIONS

Falls and Fractures – In the SPARTAN study, falls and fractures occurred in 16% and 12% of patients treated with ERLEADA compared to 9% and 7% treated with placebo respectively. Falls were not associated with loss of consciousness or seizure. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone targeted agents.

Seizure – In a randomized study (SPARTAN), two patients (0.2%) treated with ERLEADA experienced a seizure. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

ADVERSE REACTIONS

Adverse Reactions – The most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.

Laboratory Abnormalities

Hematology: anemia ERLEADA 70% (Grade 3-4 0.4%) placebo 64% (Grade 3-4 0.5%) leukopenia ERLEADA 47% (Grade 3-4 0.3%) for, placebo 29% (Grades 3-4 0%), lymphopenia ERLEADA 41% (Grade 3-4 2%), placebo 21% (Grade 3-4 2%);
Chemistry – hypercholesterolemia ERLEADA 76%(Grade3-4 0.1%), placebo 46% (Grade 3-4 0%); hypertriglycemia ERLEADA 70%(Grade 3-4 2%) Placebo 59% (0.8%); hypertriglyceridemia ERLEADA 67%(Grade 3-4 2%) placebo 49%(Grade 3-4 0.8%); Hyperkalemia ERLEADA 32%(Grade 3-4 2%) Placebo 22%(Grade 3-4 0.5%)
Rash – Rash was most commonly described as macular or maculo-papular. Adverse reactions were 24% with ERLEADA versus 6% with placebo. Grade 3 rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA treatment (5%) versus placebo (0.3%).

The onset of rash occurred at a median of 82 days. Rash resolved in 81% of patients within a median of 60 days (range: 2 to 709 days) from onset of rash. Four (4%) of patients treated with ERLEADA received systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with ERLEADA.

Hypothyroidism – Hypothyroidism was reported for 8% of patients treated with ERLEADA and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was Day 113. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.

Effect of Other Drugs on ERLEADA – Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary however, reduce the ERLEADA dose based on tolerability [see Dosage and Administration (2.2)].

DRUG INTERACTIONS

Effect of ERLEADA on Other Drugs – ERLEADA is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA and evaluate for loss of activity.

P-gp, BCRP or OATP1B1 substrates – Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with ERLEADA and evaluate for loss of activity if medication is continued.

On February 14, 2018 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported that it will host a live conference call and webcast at 8:30 a.m. ET on Wednesday, February 21, 2018 to report its fourth quarter and full year 2017 financial results and provide a corporate update (Press release, Blueprint Medicines, FEB 14, 2018, View Source;p=RssLanding&cat=news&id=2332382 [SID1234523965]).

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To access the live conference call, please dial 1-855-728-4793 (domestic) or 1-503-343-6666 (international), and refer to conference ID 3391675. A live webcast will be available under "Events and Presentations" in the Investors section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.