On May 7, 2019 Pfizer Inc. (NYSE: PFE) reported that the European Commission (EC) granted conditional marketing authorization for LORVIQUA (lorlatinib, available in the U.S., Canada and Japan under the brand name LORBRENA), as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI (Press release, Pfizer, MAY 7, 2019, View Source [SID1234535832]). LORVIQUA is a third-generation ALK TKI that was specifically developed to penetrate the blood brain barrier, in the presence or absence of resistance mutations.

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"Pfizer has worked to pioneer biomarker-driven medicine for patients with ALK-positive non-small cell lung cancer and we continue to advance patient care with the approval of LORVIQUA," said Andreas Penk, M.D., regional president, Oncology International Developed Markets at Pfizer. "We are proud that LORVIQUA is our second lung cancer medication approved in Europe within two months and our third biomarker-driven medicine for lung cancer. We look forward to making LORVIQUA available for European patients with ALK-positive non-small cell lung cancer who have progressed on prior therapy with a second generation ALK medicine."

The conditional marketing authorization was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs. A total of 139 patients with ALK-positive metastatic NSCLC after treatment with at least one second-generation ALK TKI, such as alectinib, brigatinib or ceritinib, were enrolled in the Phase 2 portion of the study. Among these patients, the overall response rate (ORR) for those who have been treated with one prior ALK TKI (N=28) was 42.9% (95% CI: 24.5, 62.8) and 39.6% (95% CI: 30.5, 49.4) for those with two or more prior ALK TKI treatments (N=111). In the trial, 67% of patients had a history of brain metastases.

"Over the last decade, our understanding of ALK-positive non-small cell lung cancer has advanced dramatically, leading to multiple medications for patients. However, the common challenges associated with treating the disease, including resistance and brain metastases have created an urgent need for additional treatment options," said Enriqueta Felip, M.D., Ph.D., Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology in Spain. "The LORVIQUA approval marks an exciting time in lung cancer innovation and I look forward to using this next-generation ALK inhibitor to treat my patients."

Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received LORVIQUA 100 mg once daily in study B7461001, the most common (≥ 20%) adverse reactions were hypercholesterolemia (84.4%), hypertriglyceridemia (67.1%), edema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%), arthralgia (24.7%), mood effects (22.7%) and diarrhea (22.7%).

Conditional approval is granted to a medicinal product that fulfils an unmet medical need, where the benefit-risk balance is positive and the benefit of the product’s immediate availability outweighs the risk of less comprehensive data than normally required.1 Under the provisions of the conditional approval, Pfizer will provide additional data from the post-marketing studies, including the Phase 3 CROWN study of LORVIQUA versus crizotinib in the first-line treatment of patients with ALK-positive NSCLC, which is currently ongoing.

About LORVIQUA (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORVIQUA is approved in the EU as monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after:

alectinib or ceritinib as the first ALK TKI therapy; or
crizotinib and at least one other ALK TKI.
LORVIQUA is also approved:

Under the brand name LORBRENA in Japan for the treatment of ALK fusion gene-positive unresectable advanced and/or recurrent NSCLC with resistance or intolerance to ALK tyrosine kinase inhibitor(s).
Under the brand name LORBRENA in Canada, where it is conditionally approved as monotherapy for the treatment of adult patients with ALK-positive metastatic NSCLC who have progressed on: crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib or alectinib.
Under the brand name LORBRENA 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.
The U.S. 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.

LORBRENA (lorlatinib) IMPORTANT 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. 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. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume at the 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. 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. 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 edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea; the most common (≥20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

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. Concomitant use of LORBRENA decreases the concentration of CYP3A 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.

Please see full prescribing information for LORBRENA in the U.S. here.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.2 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis.3

ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients.4,5 Epidemiology studies suggest that approximately three to five percent of NSCLC tumors are ALK-positive.6

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.

On May 7, 2019 Premier Inc. (NASDAQ: PINC) reported financial results for the fiscal 2019 third quarter ended March 31, 2019 (Press release, Premier, MAY 7, 2019, View Source [SID1234535849]).

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The company adopted new revenue recognition standard ASC 606 on July 1, 2018, in conjunction with the beginning of fiscal 2019, using the modified retrospective approach and did not restate prior periods. Therefore, fiscal 2019 results of operations under the new revenue standard ASC 606 are compared with fiscal 2018 results under the previous revenue standard ASC 605 in the body of this press release, and the comparisons are not necessarily meaningful. However, solely for informational purposes, current period results under the previous standard are included in the tables at the back of this press release.

Q3 2019 Highlights:

GAAP net revenue was $422.9 million, compared with $425.3 million a year ago; Supply Chain Services segment revenue was $330.2 million, compared with $330.7 million a year ago; and Performance Services segment revenue was $92.6 million, compared with $94.6 million a year ago.
GAAP net income was $73.8 million, compared with $76.5 million a year ago, and diluted net income was $0.48 per share, compared with a loss of $1.93 per share a year ago.
Non-GAAP adjusted EBITDA* was $137.6 million, compared with $142.2 million a year ago.
Non-GAAP adjusted fully distributed net income* was $84.7 million, or $0.66 per diluted share, compared with $90.6 million, or $0.67 per diluted share a year ago.
Nine-month results demonstrate financial performance remains on track with existing guidance ranges for the full fiscal year, with net administrative fees up 4% from a year ago, supply chain services and performance services revenue up 1% and 3%, respectively, non-GAAP adjusted EBITDA up 6% and non-GAAP adjusted fully distributed earnings per share up 22%.
For full fiscal-year, Supply Chain Services revenue projected to perform near midpoint of existing range, Performance Services segment revenue near higher end of the range, non-GAAP adjusted EBITDA near lower end of the range, and non-GAAP adjusted fully distributed earnings per share near midpoint of the range.
Outlook raised for full fiscal-year non-GAAP free cash flow, which is now expected to exceed 55% of non-GAAP adjusted EBITDA for the full fiscal year.
On April 26, 2019, Premier’s board of directors authorized an additional $300.0 million for the potential repurchase of Class A stock, following the completion of the previous $250.0 million repurchase program during the fiscal third quarter.
* Descriptions of non-GAAP financial measures are provided in "Use and Definition of Non-GAAP Financial Measures," and reconciliations are provided in the tables at the end of this release.

"Our fiscal third-quarter results reflect the timing-related impact of revenue recognition under the new ASC 606 revenue standard, continuing headwinds in our products business, and, to a lesser extent, incremental investments in future growth opportunities that we believe will enhance our core capabilities across the supply chain, enterprise analytics and performance improvement businesses," said Susan DeVore, chief executive officer. "While our results are consistent with our expectation that the second half of our fiscal year would be less profitable than the first half, we remain on track to deliver full fiscal-year 2019 results within our previously disclosed guidance ranges.

"We are actively managing Premier’s portfolio, as underscored by our decision to exit the specialty pharmacy business, and focusing on our core capabilities to deliver best-in-class solutions for our member health systems and sustainable, long-term value creation for stockholders," DeVore continued. "The company’s flexible balance sheet and strong cash flow provide a solid foundation and support our balanced approach to pursuing both organic and external growth opportunities while returning capital to stockholders. The board’s decision to authorize a new $300.0 million stock repurchase program underscores its continued confidence in our strategy."

On May 7, 2019 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL), reported financial results for the first quarter ended March 31, 2019, including sales of TAVALISSE (fostamatinib disodium hexahydrate), for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, MAY 7, 2019, View Source [SID1234535865]).

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"Since the U.S. launch of TAVALISSE one year ago, a growing number of physicians are utilizing our product in earlier lines of therapy and with an increasing number of their chronic ITP patients," stated Raul Rodriguez, president and CEO. "Internationally, the recent collaboration with Grifols in Europe enhances our potential access to a majority of the ex-U.S. ITP market. Meanwhile, our pipeline is expanding with the initiation of our Phase 3 trial in warm autoimmune hemolytic anemia and additional ongoing clinical and research projects."

Financial Update

For the first quarter of 2019, Rigel reported a net loss of $17.6 million, or $0.11 per share, compared to a net loss of $24.4 million, or $0.17 per share, in the same period of 2018.

For the first quarter of 2019, Rigel reported total revenues of $12.6 million, consisting of $8.1 million in net product sales of TAVALISSE and $4.6 million in contract revenues from collaborations. The increase in net product sales of TAVALISSE reflects the continuing growth of its business since commercial launch in May 2018. There were no net product sales nor contract revenues from collaborations in the first quarter of 2018.

Contract revenues from collaborations of $4.6 million during the three months ended March 31, 2019 primarily related to a portion of the $30.0 million upfront fee recognized as revenue upon delivery of license rights to Grifols, S.A. and Rigel’s performance of certain research and development services. There were no contract revenues from collaborations during the three months ended March 31, 2018.

Rigel reported total costs and expenses of $31.0 million in the first quarter of 2019, compared to $24.7 million for the same period in 2018. The increase in costs and expense was primarily due to the increases in personnel costs, including its customer-facing and medical affairs teams, and third-party costs to support Rigel’s commercialization of TAVALISSE.

As of March 31, 2019, Rigel had cash, cash equivalents and short-term investments of $127.9 million, compared to $128.5 million as of December 31, 2018.

Business Update

Rigel’s launch of TAVALISSE in the U.S. continued to build upon its early success with growth driven by expansion of the prescriber base, steady use of the product as an early treatment option in steroid refractory patients, physicians prescribing to an increased number of patients, and strong reimbursement from the payer community.
Rigel advanced the regulatory review of fostamatinib in chronic ITP by responding to day-120 questions from the European Medicines Agency (EMA) and remains on track for potential approval in the EU by the end of 2019.
In January, Rigel entered into a collaboration with Grifols, S.A. for the rights to fostamatinib in all indications in Europe and Turkey enabling a commercial launch preparation well ahead of the anticipated approval date.
Kissei Pharmaceuticals, Rigel’s collaborator in Japan, has initiated discussions with the Pharmaceuticals and Medical Devices Agency (PMDA) to define a path towards fostamatinib approval in Japan.
In warm AIHA, Rigel opened clinical trial sites for its pivotal Phase 3 clinical study of fostamatinib. The clinical trial protocol calls for approximately 80 patients in a 24-week study with enrollment of the first patient expected this month. Topline trial results are projected in early 2021, positioning fostamatinib to potentially be the first FDA-approved treatment for this indication.
The company’s research and development team continues to investigate potential molecules that modulate the immune system, including R835, Rigel’s IRAK 1/4 inhibitor currently in Phase 1 development. In addition, Rigel has four partnered programs that are in Phase 1 and 2 of their clinical development and continue to advance.
About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients are adequately treated with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA
AIHA is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body’s own red blood cells. AIHA affects approximately 40,000 adult patients in the U.S. and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients.

About R8351
The investigational candidate, R835, is an orally available, potent and selective inhibitor of IRAK1 and IRAK4 that has been shown preclinically to block inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 (IL-1R) family receptor signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to a variety of inflammatory conditions. R835 is active in multiple rodent models of inflammatory disease including psoriasis, arthritis, lupus, multiple sclerosis and gout. The safety and efficacy of R835 has not been established by the FDA or any healthcare authority.

Conference Call and Webcast with Slides Today at 4:30PM Eastern Time
Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time).

Participants can access the live conference call by dialing 855-892-1489 (domestic) or 720-634-2939 (international) and using the Conference ID number 3999559. The webcast, with slide presentation, can be accessed from Rigel’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (e.g., rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (e.g., digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

On May 7, 2019 AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) reported unaudited consolidated financial results for the first quarter ended March 31, 2019 and provided a business update (Press release, AMAG Pharmaceuticals, MAY 7, 2019, View Source [SID1234535793]).

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Total revenue for the first quarter of 2019 was $75.8 million, compared with $117.4 million in the same period last year. Makena (hydroxyprogesterone caproate injection) revenues were $31.3 million in the first quarter, compared with $90.0 million in the same period last year. This decline was primarily due to the mid-2018 entry of generic competition to the Makena intramuscular (IM) product, as well as IM supply constraints in the quarter (described below). Feraheme (ferumoxytol injection) first quarter 2019 revenues increased to a record $40.0 million, or 59%, over the same period last year. Intrarosa (prasterone) realized significant growth in net price as well as volume growth in the first quarter of 2019, as compared to the prior year period.

The company reported an operating loss of $117.7 million in the first quarter of 2019, compared with an operating loss of $50.8 million in the first quarter of 2018. Included in the loss in the first quarter of 2019 was a $74.9 million accounting impact related to the acquisition of Perosphere Pharmaceuticals Inc., which closed in the quarter. Consistent with its strategic plan and 2019 financial guidance, the company reported negative adjusted EBITDA of $26.6 million in the first quarter of 2019, compared with positive adjusted EBITDA of $30.0 million in the first quarter of 2018.1

"While total Makena revenues in the first quarter were adversely impacted by a number of non-recurring charges, we are encouraged by the strong underlying demand for the subcutaneous auto-injector, and the progress made to replace our previous primary supplier of Makena IM with new inventory from two suppliers this second quarter," said William Heiden, AMAG’s president and chief executive officer. "We’re also proud of our Feraheme team and the continued growth that product has realized. The significant cash flow from these products helps fund the development of our novel pipeline assets, which we believe are the future value drivers of the company."

"In the first quarter, our development pipeline continued to progress nicely. We are eagerly awaiting a decision on the upcoming PDUFA date for VyleesiTM (bremelanotide) and the mid-year initiation of the Phase 3a clinical studies for ciraparantag," continued Mr. Heiden. "We look forward to discussing more about AMAG’s future at our Analyst Day that will be held on May 22 in New York, which will include panels for AMAG-423, Vyleesi and ciraparantag of key opinion leaders who will provide their expert views on the opportunity for and value of these new product candidates."

1 See summaries of GAAP to non-GAAP adjustments at the conclusion of this press release.

1

First Quarter 2019 and Recent Business Highlights:
•
Promoted Tony Casciano to chief commercial officer; Mr. Casciano led the successful launches of the Makena SC auto-injector and the Feraheme broad label
•
Achieved 59% growth in Feraheme net sales year-over-year
•
Makena SC auto-injector achieved 40% volume growth and captured 54% market share of all FDA-approved hydroxyprogesterone caproate prescription volume over the fourth quarter of 2018
•
Improved first quarter 2019 Intrarosa gross-to-net price by more than 30% over the fourth quarter of 2018; successfully combined and cross trained the women’s health and maternal health sales forces into one team of approximately 125 sales representatives
•
Acquired Perosphere Pharmaceuticals, including ciraparantag, a development-stage drug candidate to reverse the anticoagulant effects of novel oral anticoagulants (NOACs) and low molecular weight heparin (LMWH)
•
Completed the study and submitted ambulatory blood pressure data to the FDA and continued activities supporting the potential launch of Vyleesi (PDUFA date: June 23, 2019)
•
Data presentations:
–
New and encore data related to Vyleesi for the treatment of hypoactive sexual desire disorder (HSDD) at the International Society for the Study of Women’s Sexual Health (ISSWSH)/International Society for Sexual Medicine (ISSM) joint meeting
–
New data related to Vyleesi for the treatment of HSDD and Feraheme related to iron deficiency anemia (IDA) resulting from abnormal uterine bleeding at the American College of Obstetricians and Gynecologists (ACOG) Annual Clinical and Scientific Meeting
•
Reaffirmed 2019 financial guidance

First Quarter Ended March 31, 2019 (unaudited)
Total revenues for the first quarter of 2019 were $75.8 million, compared with $117.4 million in the first quarter of 2018. First quarter 2019 net product sales of Makena were $31.3 million, which were lower than the $90.0 million reported in the first quarter of 2018, primarily due to the mid-2018 entry of generic competition to the Makena IM product, as well as IM supply constraints. Makena revenues in the first quarter of 2019 were further impacted by a number of gross-to-net charges, including: (i) $3.5 million of failure-to-supply penalties related to a temporary authorized generic (AGx) IM out of stock situation that occurred during the first quarter, (ii) approximately $5.0 million of increased Medicaid rebates related to the IM supply constraints in the quarter and best price implications, and (iii) $6.0 million change in estimate for Medicaid liability for prior period sales of the Makena IM product. The company expects to resolve its Makena IM supply constraints in the second quarter of 2019 and, therefore, believes charges (i) and (ii) described above are non-recurring in nature. During the first quarter of 2019, the company did not record any branded Makena IM revenues, and revenues for the AGx were adversely impacted by IM supply constraints. Sales of the Makena SC auto-injector totaled $37.8 million in the first quarter of 2019, which is net of the $5.0 million additional Medicaid rebates referenced above. Sales of Feraheme and MuGard increased 59% to $40.1 million in the first quarter of 2019, compared with $25.2 million in the first quarter of 2018. Intrarosa contributed $4.4 million in net sales during the first quarter of 2019, compared with $2.2 million in the same period last year.

Operating expenses, including cost of product sales, were aligned with expectations, totaling $193.5 million in the first quarter of 2019, compared with $168.2 million for the same period in 2018. This increase was primarily due to: (i) the $74.9 million acquired in-process research and development charge related to the acquisition of Perosphere, (ii) a one-time restructuring charge of $7.4 million related to combining the company’s women’s health and maternal health sales forces, and (iii) higher research and development costs of $7.3 million related to the company’s ongoing clinical development programs. These increases in operating expenses were partially off-set by a $45.4 million reduction in cost of product sales, driven primarily by lower intangible amortization expense.

2

The company reported an operating loss from continuing operations in the first quarter of 2019 of $117.7 million, compared with an operating loss of $50.8 million for the same period last year, largely due to the Perosphere acquisition described above. The company reported a net loss from continuing operations of $122.1 million, or $3.54 loss per basic and diluted share, for the first quarter of 2019, compared with a net loss from continuing operations of $58.1 million, or $1.70 loss per basic and diluted share, for the same period in 2018. The net loss reported during the first quarter on 2019 was favorably impacted by a reduction in interest expense incurred, as compared to the prior year period. This was the result of the company retiring $475 million in high-yield bonds in the third quarter of 2018.

Non-GAAP adjusted EBITDA from continuing operations for the first quarter of 2019 was ($26.6) million, compared with $30.0 million in the first quarter of 2018.

Balance Sheet Highlights
As of March 31, 2019, the company’s cash and investments totaled $266.5 million, and long-term total debt totaled $320.0 million (representing the principal amounts outstanding of the 2022 convertible notes). Cash used during the first quarter of 2019 included: (i) $70.8 million related to the acquisition of Perosphere Pharmaceuticals, (ii) $21.4 million for the repayment of the balance of the company’s 2019 Convertible Note, and (iii) $13.7 million for the repurchase of approximately 1.1 million shares of common stock.

2 See reconciliations of 2019 GAAP to non-GAAP financial guidance at conclusion of this press release.
3 As previously reported, the 2019 operating loss guidance range issued in January 2019 excluded the potential accounting impact for the acquisition of Perosphere, which had not closed at that time. The operating loss guidance range has now been adjusted to incorporate the $74.9 million accounting impact of the Perosphere acquisition, which was recorded in the first quarter of 2019.

"We’re pleased with the market uptake of the Makena SC auto-injector, which captured more than 50 percent share of patients treated with FDA-approved hydroxyprogesterone caproate in the first quarter, underscoring continued strong physician demand of this differentiated product and the sustainability of the Makena franchise," said Ted Myles, AMAG’s chief financial officer. "With the expected return of Makena IM supply in the second quarter, continued strong underlying demand for the SC auto-injector, impressive performance from Feraheme, as well as encouraging leading indicators from our Intrarosa direct-to-consumer campaign, we are reiterating our full year guidance for 2019."

Conference Call and Webcast Access
AMAG Pharmaceuticals, Inc. will host a conference call and webcast today at 8:00 a.m. ET to discuss the company’s first quarter 2019 financial results, recent business highlights and 2019 outlook.

Dial-in Number
U.S./Canada dial-in number: (877) 412-6083
International dial-in number: (702) 495-1202
Conference ID: 6850648

Replay dial-in number: (855) 859-2056
Replay International dial-in number: (404) 537-3406
Conference ID: 6850648

A telephone replay will be available from approximately 11:00 a.m. ET on May 7, 2019 through midnight on May 14, 2019. The webcast with slides will be accessible through the Investors section of AMAG’s website at www.amagpharma.com. A replay of the webcast will be archived on the website for 30 days.

Use of Non-GAAP Financial Measures
AMAG has presented certain non-GAAP financial measures, including non-GAAP costs and expenses and non-GAAP adjusted EBITDA (earnings before income taxes, depreciation and amortization). These non-GAAP financial measures exclude certain amounts, expenses or income, from the corresponding financial measures determined in accordance with accounting principles generally accepted in the U.S. (GAAP). Management believes this non-GAAP information is useful for investors, taken in conjunction with AMAG’s GAAP financial statements, because it provides greater transparency regarding AMAG’s operating performance. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of AMAG’s operating results as reported under GAAP, not as a substitute for GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.

On May 7, 2019 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the first quarter 2019 and provided an operational update (Press release, Bellicum Pharmaceuticals, MAY 7, 2019, View Source [SID1234535817]).

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"We made strong progress in advancing our programs in the first quarter," said Rick Fair, President and Chief Executive Officer of Bellicum Pharmaceuticals. "In our GoCAR-T pipeline, we received acceptance of our abstract with new data from the BPX-601 Phase 1/2 clinical trial for the upcoming ASCO (Free ASCO Whitepaper) Annual Meeting, and made progress toward IND clearance and Phase 1 study start for BPX-603 later this year. In addition, we remain on track to announce topline results from the rivo-cel pediatric registrational trial by the end of the second quarter."

PROGRAM HIGHLIGHTS AND CURRENT UPDATES

BPX-601 GoCAR-T

Bellicum presented initial clinical data from the dose-escalation phase of the Phase 1/2 study of BPX-601 at the Gastrointestinal Cancers Symposium in January that showed a promising safety profile. Additionally, in several patients reported, iMC activation from the administration of rimiducid led to enhanced cell expansion, prolonged cell persistence, and early evidence of clinical activity and disease control. The trial protocol was amended to incorporate a standard lymphodepletion conditioning regimen consisting of cyclophosphamide/fludarabine (Cy/Flu). Updated data from this study—including patients from this Cy/Flu cohort—have been accepted for presentation at ASCO (Free ASCO Whitepaper). As a next step in the study, Bellicum plans to enroll an additional cohort to evaluate repeat rimiducid dosing to re-activate iMC over time, which is intended to deepen and extend the treatment effect. Initial results from this cohort are expected in late 2019.
Controllable Dual-Switch GoCAR-T Product Candidates

Bellicum believes that its next-generation dual-switch GoCAR-T technology may enhance efficacy relative to current generation CAR-T therapy through iMC activation while enabling clinicians to manage certain treatment-emergent toxicities with CaspaCIDe. The company expects to complete an IND application and initiate a Phase 1 clinical trial for BPX-603, a dual-switch GoCAR-T targeting HER2-expressing solid tumors, later this year. The company also expects to submit an IND application by the end of the year for BPX-802, a dual-switch GoCAR-T product candidate targeting an antigen expressed in hematological malignancies.
Rivo-cel

The company expects to report topline results from the pediatric BP-004 study in the second quarter of 2019 and plans to submit Marketing Authorisation Applications (MAAs) for rivo-cel and rimiducid by year-end. Patient recruitment is ongoing in THRIVE, a pivotal randomized global Phase 2/3 clinical trial of rivo-cel in adult and adolescent patients 12 years and older with intermediate and high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
First Quarter 2019 Financial Results

Cash Position and Guidance: Bellicum reported cash, restricted cash and investments totaling $78.1 million as of March 31, 2019, compared to $98.0 million at December 31, 2018. Based on current operating plans, Bellicum expects that current cash resources will be sufficient to meet operating requirements through the end of 2019. During the first quarter, Bellicum utilized its at the market financing facility selling 1.4 million shares for net cash proceeds of $4.6 million.

R&D Expenses: Research and development (R&D) expenses were $16.8 million for the first quarter of 2019, compared to $16.5 million for the first quarter of 2018. The higher expenses in the first quarter of 2019 resulted primarily from higher expenditures related to the GoCAR-T platform including initiation of additional clinical sites and costs related to IND filing.

G&A Expenses: General and administrative (G&A) expenses were $7.5 million for the first quarter of 2019 compared to $5.7 million during the comparable period in 2018. The higher expenses in the first quarter 2019 relative to the comparable period in 2018 were primarily due to increased personnel related costs due to hiring additional employees as well as increased costs related to commercialization preparation activities.

Net Loss: Bellicum reported a net loss of $24.5 million for the first quarter of 2019 compared to a net loss of $22.8 million for the first quarter of 2018. The results included non-cash, share-based compensation charges of $2.1 million and $3.6 million for the first quarter of 2019 and 2018, respectively.

Shares Outstanding: At April 30, 2019, Bellicum had 46,009,066 shares of common stock outstanding.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for solid tumors expressing prostate stem cell antigen (PSCA), including pancreatic, gastric, and prostate cancers.

About Rivo-cel (BPX-501)

Rivo-cel (rivogenlecleucel) is an allogeneic polyclonal T-cell product designed to accelerate immune recovery after HSCT and to reduce relapse of leukemia following a stem cell transplant. The cell treatment contains a diverse repertoire of T cells which may contribute to a robust graft vs. leukemia effect. Rivo-cel’s anti-infective benefits may also reduce morbidity and mortality, as patients are highly susceptible to infection following a transplant. The product’s CaspaCIDe safety switch enables this approach by allowing physicians to reduce the number of alloreactive cells in the event of uncontrolled GvHD. Rivo-cel addresses a major unmet need in adult and pediatric leukemia, lymphoma and inherited blood disease patients following a haploidentical stem cell transplant.