On April 25, 2019 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported financial results for the first quarter of 2019 (Press release, Alexion, APR 25, 2019, View Source [SID1234535384]). Total revenues in the first quarter were $1,140.4 million, a 23 percent increase compared to the same period in 2018. The negative impact of foreign currency on total revenues year-over-year was 1 percent, or $12.3 million, inclusive of hedging activities. On a GAAP basis, diluted EPS in the quarter was $2.61, a 135 percent increase versus the prior year. Non-GAAP diluted EPS for the first quarter of 2019 was $2.39, a 42 percent increase versus the first quarter of 2018.

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"We had a great start to 2019, with a strong launch in ULTOMIRIS’ first full quarter since FDA approval. We’ve also made significant progress executing and expanding our pipeline. This progress includes three business development deals, multiple filings under regulatory review and having begun dosing patients in two new ULTOMIRIS Phase 3 programs," said Ludwig Hantson, Ph.D., Chief Executive Officer of Alexion. "We look forward to continuing to build on our momentum as the year progresses, further growing our four durable franchises in hematology/nephrology, neurology, metabolics and FcRn."

First Quarter 2019 Financial Highlights

Total net product sales were $1,140.2 million in the first quarter of 2019, compared to $930.4 million in the first quarter of 2018.
SOLIRIS (eculizumab) net product sales were $962.0 million, compared to $800.1 million in the first quarter of 2018, representing a 20 percent increase. SOLIRIS volume increased 23 percent year-over-year.
ULTOMIRIS (ravulizumab-cwvz) net product sales were $24.6 million in its first full quarter since FDA approval.
STRENSIQ (asfotase alfa) net product sales were $130.1 million, compared to $110.7 million in the first quarter of 2018, representing an 18 percent increase. STRENSIQ volume increased 26 percent year-over-year.
KANUMA (sebelipase alfa) net product sales were $23.5 million, compared to $19.6 million in the first quarter of 2018, representing a 20 percent increase. KANUMA volume increased 28 percent year-over-year.
GAAP cost of sales was $85.8 million, compared to $91.6 million in the first quarter of 2018. Non-GAAP cost of sales was $82.1 million, compared to $83.0 million in the first quarter of 2018.
GAAP R&D expense was $195.9 million, compared to $176.6 million in the first quarter of 2018. Non-GAAP R&D expense was $159.4 million, compared to $161.6 million in the first quarter of 2018.
GAAP SG&A expense was $281.5 million, compared to $257.1 million in the first quarter of 2018. Non-GAAP SG&A expense was $243.7 million, compared to $220.4 million in the first quarter of 2018.
GAAP income tax benefit was $46.1 million, compared to income tax expense of $102.5 million in the first quarter of 2018. GAAP income tax benefit for the first quarter 2019 includes deferred tax benefits of $95.7 million and $30.3 million associated with a tax election related to intellectual property and release of an existing valuation allowance, respectively. Non-GAAP income tax expense was $100.9 million, compared to $68.6 million in the first quarter of 2018.
GAAP diluted EPS was $2.61, compared to $1.11 in the first quarter of 2018. GAAP diluted EPS for the first quarter 2019 includes deferred tax benefits of $95.7 million and $30.3 million associated with a tax election related to intellectual property and release of an existing valuation allowance, respectively. Non-GAAP diluted EPS was $2.39, compared to $1.68 in the first quarter of 2018.
Research and Development

PHASE 3

SOLIRIS – Neuromyelitis Optica Spectrum Disorder (NMOSD): In February 2019, Alexion announced that the U.S. Food and Drug Administration (FDA) granted Priority Review for SOLIRIS in NMOSD and set a Prescription Drug User Fee Act (PDUFA) action date of June 28, 2019. Alexion has filed for regulatory approval in the European Union (EU) and Japan, and orphan drug priority review has been granted in Japan. These filings are based on previously announced results from the Phase 3 PREVENT study, in which 97.9 percent of patients with anti-aquaporin-4 (AQP4) auto antibody-positive NMOSD who received SOLIRIS on top of stable standard-of-care therapy were relapse free at 48 weeks compared to 63.2 percent of patients who received placebo.
ULTOMIRIS – Paroxysmal Nocturnal Hemoglobinuria (PNH): Applications for approval in the EU and Japan are currently under review. In addition, a Phase 3 study of ULTOMIRIS in children and adolescents with PNH is underway.
ULTOMIRIS – Atypical Hemolytic Uremic Syndrome (aHUS): In April 2019, Alexion submitted an application in the U.S. for the approval of ULTOMIRIS in patients with aHUS. The filing was based on previously announced positive topline results from a Phase 3 study of ULTOMIRIS in complement inhibitor naïve patients with aHUS. Alexion plans to file for regulatory approval in the EU and Japan in 2019. In addition, a Phase 3 study of ULTOMIRIS in adolescents and children with aHUS is underway.
ULTOMIRIS – Subcutaneous: Enrollment and dosing are underway in a single, PK-based Phase 3 study of ULTOMIRIS delivered subcutaneously once per week to support registration in PNH and aHUS. Data are expected in early 2020.
ULTOMIRIS – Generalized Myasthenia Gravis (gMG): In the first quarter of 2019, Alexion initiated a Phase 3 study of ULTOMIRIS in gMG.
ULTOMIRIS – Neuromyelitis Optica Spectrum Disorder (NMOSD): Alexion plans to initiate a Phase 3 study of ULTOMIRIS in NMOSD by the end of 2019.
ALXN1840 (WTX101) – Wilson Disease: Enrollment and dosing are underway in a Phase 3 study of ALXN1840 (WTX101) in Wilson disease, a rare genetic disorder with devastating hepatic and neurological consequences. The study is now powered for superiority versus standard-of-care therapy. ALXN1840 is a first-in-class oral copper-binding agent with a unique mechanism of action to bind serum copper and promote its removal from the liver.

PHASE 1/2

ALXN1830 (SYNT001): Alexion plans to initiate two Phase 2/3 trials of ALXN1830 (SYNT001) in late 2019 or early 2020 – one in warm autoimmune hemolytic anemia (WAIHA) and one in gMG.
ALXN1810 – Subcutaneous: In the first quarter of 2019, Alexion completed dosing in a Phase 1 study of subcutaneous ALXN1210 co-administered with Halozyme’s ENHANZE drug-delivery technology, recombinant human hyaluronidase enzyme (rHuPH20), a next-generation subcutaneous formulation called ALXN1810.
ULTOMIRIS – Amyotrophic Lateral Sclerosis (ALS): Alexion plans to initiate a proof-of-concept study for ULTOMIRIS in ALS.
ULTOMIRIS – Primary Progressive Multiple Sclerosis (PPMS): Alexion plans to initiate an exploratory clinical study of ULTOMIRIS in PPMS.
Caelum Biosciences – CAEL-101 – Light Chain (AL) Amyloidosis: In January 2019, Alexion entered into a collaboration with Caelum Biosciences to develop CAEL-101 for AL amyloidosis, a rare systemic disorder that causes misfolded immunoglobulin light chain protein to build up in and around tissues, resulting in progressive and widespread organ damage. CAEL-101 is a first-in-class amyloid fibril targeted therapy designed to improve organ function by reducing or eliminating amyloid deposits in patients with AL amyloidosis. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in patients with relapsed and refractory AL amyloidosis. Pending regulatory feedback, a Phase 2/3 study investigating CAEL-101 as an add-on to current standard-of-care therapy is planned to begin in early 2020.
Affibody AB – ABY-039: In March 2019, Alexion announced a partnership with Affibody AB to co-develop ABY-039 for rare Immunoglobulin G (IgG)-mediated autoimmune diseases. Pending relevant regulatory approvals, the transaction is expected to close in the second quarter of 2019. Currently in Phase 1 development, ABY-039 is a bivalent antibody-mimetic that targets the neonatal Fc receptor (FcRn). ABY-039 has been specifically designed to combine Affibody’s protein therapeutics platform (Affibody molecules) and Albumod technology to achieve a long half-life, which, along with its small size provides the potential for less frequent, convenient, at-home subcutaneous administration.

PRE-CLINICAL

ALXN1720: In March 2019, Alexion announced the development of ALXN1720, a novel anti-C5 albumin-binding bi-specific mini-body that binds and prevents activation of human C5. Alexion plans to initiate a first-in-human study of ALXN1720 in late 2019.
Zealand Pharma A/S: In March 2019, Alexion began a collaboration with Zealand Pharma A/S to discover and develop novel peptide therapies for up to four targets in the complement pathway. Peptides offer a number of advantages, including being highly selective and potent, allowing low dosage volumes for ease of administration, and having the potential to treat a broad range of complement-mediated diseases.
Dicerna – GalXC: Alexion is collaborating with Dicerna Pharmaceuticals to jointly discover and develop up to four subcutaneously delivered GalXC RNA interference (RNAi) candidates, currently in pre-clinical development, for the treatment of complement-mediated diseases.
Complement Pharma – CP010: Alexion is collaborating with Complement Pharma to co-develop CP010, a pre-clinical C6 inhibitor that has the potential to treat multiple neurological disorders.

GAAP guidance reflects the financial impact of the announced collaboration with Affibody.
GAAP effective tax rate of 7 to 9 percent; non-GAAP effective tax rate of 14 to 16 percent.
Alexion’s financial guidance is based on current foreign exchange rates net of hedging activities and does not include the effect of acquisitions, license and collaboration agreements, intangible asset impairments, litigation charges, changes in fair value of contingent consideration or restructuring and related activity outside of the previously announced activities that may occur after the issuance of this press release.

Conference Call/Webcast Information:

Alexion will host a conference call/audio webcast to discuss the first quarter 2019 results today at 8:00 a.m. Eastern Time. To participate in the call, dial 866-762-3111 (USA) or 210-874-7712 (International), conference ID 1692605 shortly before 8:00 a.m. Eastern Time. A replay of the call will be available for a limited period following the call. The audio webcast can be accessed on the Investor page of Alexion’s website at: View Source

On April 25, 2019 Amgen (NASDAQ:AMGN) reported that it will report its first quarter financial results on Tuesday, April 30, 2019, after the close of the U.S. financial markets (Press release, Amgen, APR 25, 2019, View Source;p=RssLanding&cat=news&id=2395774 [SID1234535383]). The announcement will be followed by a conference call with the investment community at 2 p.m. PT. Participating in the call from Amgen will be Robert A. Bradway, chairman and chief executive officer, and other members of Amgen’s senior management team.

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Live audio of the conference call will be simultaneously broadcast over the internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On April 25, 2019 Eli Lilly and Company (NYSE: LLY) reported that the company has been working to facilitate the withdrawal of Lartruvo (olaratumab) from the market for the treatment of advanced soft tissue sarcoma (STS) (Press release, Eli Lilly, APR 25, 2019, View Source [SID1234535382]). Lilly’s actions to withdraw Lartruvo from the market follow the failure of the Phase 3 ANNOUNCE clinical trial, in which Lartruvo did not improve survival for patients. Lilly is establishing a program to ensure current patients will have access to Lartruvo with limited interruption after it is withdrawn from the market. The program will be established as allowed by local country regulations.

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Lilly is working to ensure that patients who are currently receiving Lartruvo may, in consultation with their physician, continue their course of therapy if they have been informed of the risks of Lartruvo and the results of the ANNOUNCE study and wish to continue, subject to local laws and regulations. No new patients should receive Lartruvo outside of participation in ongoing clinical trials.

Lilly also is working to establish a program to allow patients who are currently receiving Lartruvo to continue treatment with limited interruption after Lartruvo is withdrawn from the market, subject to local laws and regulations. More information regarding this program will be provided directly to healthcare professionals in the coming weeks.

"Lilly wants to ensure that patients and physicians feel supported during this important time," said Anne White, president, Lilly Oncology. "Advanced soft tissue sarcoma is a rare and difficult-to-treat cancer. Establishing this program will give patients who are currently taking Lartruvo the opportunity to continue their treatment program uninterrupted."

Lilly plans to present the ANNOUNCE data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019 annual meeting and will publish the results in a medical journal.

About Soft Tissue Sarcoma
Sarcomas are a diverse and relatively rare type of cancer that usually develop in the connective tissue of the body, which include fat, blood vessels, nerves, bones, muscles, deep skin tissues and cartilage. Soft tissue sarcoma (STS) is a complex disease with multiple subtypes, making it hard to diagnose and difficult to treat. According to the American Cancer Society, in 2019, an estimated 12,750 new STS cases will be diagnosed, and more than 5,000 people will not survive their disease in the U.S. alone. For decades, there have been no first-line therapeutic advancements for STS that have improved overall survival (OS).

About LARTRUVO (olaratumab)
LARTRUVO is a platelet-derived growth factor receptor alpha (PDGFR-α) blocking antibody that specifically binds PDGFR-α and prevents receptor activation. LARTRUVO exhibits in vitro and in vivo anti-tumor activity against selected sarcoma cell lines and disrupted the PDGFR-α signaling pathway in in vivo tumor implant models.

About the ANNOUNCE Trial
ANNOUNCE was a randomized, double-blind, Phase 3 study of LARTRUVO in combination with doxorubicin, followed by LARTRUVO monotherapy, versus doxorubicin plus placebo followed by placebo, in patients with advanced or metastatic STS. The two primary endpoints were OS in the intent-to-treat (ITT) population and OS in the leiomyosarcoma (LMS) sub-population. Patients with locally advanced, unresectable or metastatic STS not amenable to curative treatment were enrolled and were eligible with any prior number of treatment regimens, provided they had not previously received treatment with an anthracycline.

LARTRUVO was administered at a loading dose of 20 mg/kg on days 1 and 8 of cycle 1 and 15 mg/kg on days 1 and 8 of all subsequent cycles in combination with doxorubicin 75 mg/m2 administered on day 1 of each cycle. Placebo was administered in combination with doxorubicin for 8 cycles. LARTRUVO was continued as monotherapy until disease progression.

Key secondary endpoints included safety, progression-free survival, objective response rate, and patient-reported outcomes.

INDICATION
LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery.

This indication was approved under Accelerated Approval. Continued approval for this indication was contingent upon verification and description of clinical benefit in the confirmatory trial.

IMPORTANT SAFETY INFORMATION FOR LARTRUVO

Warnings and Precautions

Infusion-Related Reactions

Infusion-related reactions (IRR) occurred in 70 (14%) of 485 patients who received at least one dose of LARTRUVO across clinical trials. For 68 of these 70 patients (97%), the first occurrence of IRR was in the first or second cycle. Grade ≥3 IRR occurred in 11 (2.3%) of 485 patients, with one (0.2%) fatality. Symptoms of IRR included flushing, shortness of breath, bronchospasm, or fever/chills, and in severe cases symptoms manifested as severe hypotension, anaphylactic shock, or cardiac arrest. Infusion-related reactions required permanent discontinuation in 2.3% of patients and interruption of infusion in 10% of patients. All 59 patients with Grade 1 or 2 IRR resumed LARTRUVO; 12 (20%) of these patients had a Grade 1 or 2 IRR with rechallenge. The incidence of IRR in the overall safety database (N = 485) was similar (18% versus 12%) between those who did (56%) and those who did not (44%) receive premedication. Monitor patients during and following LARTRUVO infusion for signs and symptoms of IRR in a setting with available resuscitation equipment. Immediately and permanently discontinue LARTRUVO for Grade 3 or 4 IRR.
Embryo-Fetal Toxicity

Based on animal data and its mechanism of action, LARTRUVO can cause fetal harm when administered to a pregnant woman. Animal knockout models link disruption of platelet-derived growth factor receptor alpha (PDGFR-α) signaling to adverse effects on embryo-fetal development. Administration of an anti-murine PDGFR-α antibody to pregnant mice during organogenesis caused malformations and skeletal variations. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LARTRUVO and for 3 months after the last dose.
Most Common Adverse Reactions/Lab Abnormalities

The most commonly reported adverse reactions (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were nausea (73% vs 52%; 2% vs 3%), fatigue (69% vs 69%; 9% vs 3%), musculoskeletal pain (64% vs 25%; 8% vs 2%), mucositis (53% vs 35%; 3% vs 5%), alopecia (52% vs 40%; 0% vs 0%), vomiting (45% vs 19%; 0% vs 0%), diarrhea (34% vs 23%; 3% vs 0%) decreased appetite (31% vs 20%; 2% vs 0%), abdominal pain (23% vs 14%; 3% vs 0%), neuropathy (22% vs 11%; 0% vs 0%), and headache (20% vs 9%; 0% vs 0%).
The most common laboratory abnormalities (all grades; grade 3-4) occurring in ≥20% of patients receiving LARTRUVO plus doxorubicin versus doxorubicin alone were lymphopenia (77% vs 73%; 44% vs 37%), neutropenia (65% vs 63%; 48% vs 38%) and thrombocytopenia (63% vs 44%; 6% vs 11%), hyperglycemia (52% vs 28%; 2% vs 3%), elevated aPTT (33% vs 13%; 5% vs 0%), hypokalemia (21% vs 15%; 8% vs 3%), and hypophosphatemia (21% vs 7%; 5% vs 3%).
Use in Specific Populations

Lactation: Because of the potential risk for serious adverse reactions in breastfeeding infants, advise women not to breastfeed during treatment with LARTRUVO and for at least 3 months following the last dose.
For more information about LARTRUVO, please see full Prescribing Information at View Source

About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.

On April 25, 2019 Athenex, Inc. (Nasdaq: ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that it will release first quarter ended March 31, 2019 financial results on May 9, 2019 before the market opens (Press release, Athenex, APR 25, 2019, View Source;p=RssLanding&cat=news&id=2395677 [SID1234535381]). The Company will host a conference call and live audio webcast on Thursday, May 9, 2019, at 8:00am Eastern Time to discuss the financial results and provide a business update.

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To participate in the call, dial 877-407-0784 (domestic) or 201-689-8560 (international) fifteen minutes before the conference call begins and reference the conference passcode 13689379. The live conference call and replay can also be accessed via audio webcast at the Investor Relations section of the Company’s website, located at View Source

On April 24, 2019 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), and Adagene Inc., an antibody engineering and discovery company, reported that they have entered into a discovery collaboration and license agreement (Press release, ADC Therapeutics, APR 24, 2019, View Source [SID1234596063]). ADC Therapeutics will use Adagene’s SAFEbody technology to generate a masked antibody that will be combined with ADC Therapeutics’ pyrrolobenzodiazepine (PBD) cytotoxic payload technology for the development of a novel ADC against a solid tumor target.

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Adagene has developed the SAFEbody technology to produce masked antibodies that are activated to bind to an antigen in the tumor microenvironment by factors present in tumor tissues but not in healthy tissues. This enables enhanced specificity for targeting of an ADC and minimizes off-target toxicity on healthy cells, potentially enhancing the therapeutic index of the ADC.

"The SAFEbody technology requires specific conditions within the tumor microenvironment to unleash the ADC’s full therapeutic potential," said Patrick van Berkel, Senior Vice President of Research and Development at ADC Therapeutics. "Combining a SAFEbody with highly potent PBD-based payloads will allow us to develop potent new tumor-specific ADCs that depend on the unique conditions in the local tumor microenvironment for full activation."

ADC Therapeutics has entered into the agreement with Adagene for one exclusive target, with the option to leverage SAFEbody technology for one additional exclusive target. Both potential programs will focus on targets in which healthy tissue expression does not permit development of ADCs incorporating traditional antibodies.

Under the terms of the agreement, Adagene will receive research funding for the discovery phase. Upon success of the discovery collaboration, Adagene will receive an upfront payment, development and commercial milestone payments, and royalties on net sales. ADC Therapeutics has granted Adagene certain commercial rights for Greater China. No other financial terms were disclosed.

"We are very pleased to partner our SAFEbody technology with ADC Therapeutics," said Peter Luo, Chief Executive Officer and Co-Founder of Adagene. "Adagene’s innovative protein engineering ability enables us to tailor-make products to limit their on-target off-tumor toxicity. Together with ADC Therapeutics’ experience in developing ADCs with highly potent PBD payloads, we have the potential to unlock new treatment options for patients with unmet medical needs."

"We’re excited to collaborate with Adagene to work toward the next generation of masked ADCs," said Chris Martin, Chief Executive Officer at ADC Therapeutics. "As we continue evaluating our potent ADCs in ongoing clinical trials, we look forward to exploring how Adagene’s SAFEbody technology incorporated in our ADCs may enable us to further improve anti-tumor activity while minimizing side effects."