On February 5, 2019 Premier Inc. (NASDAQ: PINC) reported financial results for the fiscal 2019 second quarter ended Dec. 31, 2018 (Press release, Premier, FEB 5, 2019, View Source [SID1234533073]).

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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, results of operations under the new revenue standard ASC 606 are not indicative of what results of operations were under the previous standard ASC 605. However, for informational purposes, current period results under the previous standard are included in the tables at the back of this press release.

Q2 2019 Highlights:

GAAP net revenue increased to $421.9 million from $411.4 million a year ago; Supply Chain Services segment revenue of $327.0 million increased from $324.9 million a year ago and Performance Services segment revenue of $94.9 million increased from $86.5 million.
GAAP net income of $104.8 million increased from $19.8 million and diluted net income of $0.69 per share compared with $0.06 per diluted share a year ago.
Non-GAAP adjusted EBITDA* increased to $142.0 million from $133.5 million a year ago.
Non-GAAP adjusted fully distributed net income* increased to $88.4 million, representing $0.66 per diluted share, compared with $70.0 million, or $0.50 per diluted share a year ago.
Management reaffirms full-year fiscal 2019 guidance ranges and underlying assumptions.
* 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.

"Premier delivered another successful quarter this fiscal year, characterized by steady revenue and earnings growth across our business segments and for the company as a whole," said Susan DeVore, president and chief executive officer. "We finished the quarter with continued strong liquidity, as year-over-year non-GAAP free cash flow increased 29 percent to $114.8 million. We used our strong balance sheet and cash flow to grow our capabilities with the acquisition of Stanson Health Inc., and to return cash to stockholders through our ongoing $250.0 million stock repurchase program.

"Our financial outlook remains consistent with the full-year guidance ranges we discussed last quarter and we are reaffirming these guidance ranges today," DeVore said. "We plan to continue to move forward as a leader of our industry’s transformation to value-based care, expanding and integrating our capabilities and working closely with our member providers to help ensure ongoing success in this rapidly evolving marketplace."

(b) Earnings per share attributable to stockholders excludes the adjustment of redeemable limited partners’ capital to redemption amount and the net income attributable to non-controlling interest in Premier LP if Class B common stock is determined to be dilutive. Likewise, earnings per share attributable to stockholders includes the adjustment of redeemable limited partners’ capital to redemption amount and the net income attributable to non-controlling interest in Premier LP if Class B common stock is determined to be antidilutive. The company has corrected prior period information within the current period financial statements related to a specific component used in calculating the tax effect on Premier Inc. net income for purposes of diluted earnings (loss) per share. Diluted earnings (loss) per share for the three months ended December 31, 2017 was previously stated at ($1.66) per share and has been corrected to $0.06 per share. Diluted earnings (loss) per share for the six months ended December 31, 2017 was previously stated at ($1.30) per share and has been corrected to $0.36 per share. The company believes the correction is immaterial and the amount had no impact on the company’s overall financial condition, results of operations or cash flows.

(c) See attached supplemental financial information for reconciliation of reported GAAP results to Non-GAAP results.

For the fiscal second-quarter ended Dec. 31, 2018, Premier generated GAAP net revenue of $421.9 million, an increase of $10.5 million from net revenue of $411.4 million for the same period a year ago.

GAAP net income for the fiscal second quarter was $104.8 million, compared with $19.8 million a year ago. Year-ago net income was impacted by a decrease in the effective tax rate due to federal tax reform, resulting in a re-measurement of tax receivable agreement liabilities totaling $177.2 million, offset by an increase in tax expense of $221.2 million attributable to the re-measurement of deferred tax balances. This resulted in income tax expense of $231.5 million in the year-ago quarter, compared with $1.8 million in the current quarter. In accordance with GAAP, fiscal 2019 and 2018 second-quarter net income attributable to stockholders included non-cash adjustments of $651.7 million and $317.9 million, respectively, to reflect the change in the redemption value of limited partners’ Class B common unit ownership at the end of each period. These non-cash adjustments result primarily from changes in the number of Class B common units outstanding and the company’s stock price between periods and do not reflect results of the company’s business operations. After these non-cash adjustments, the company reported net income attributable to stockholders of $693.9 million, compared with $281.2 million for the same period a year ago. Second-quarter net income of $0.69 per diluted share compared with $0.06 for the same period a year ago. See "Calculation of GAAP Earnings per Share" in the income statement section of this press release.

Fiscal second-quarter non-GAAP adjusted EBITDA increased to $142.0 million from $133.5 million for the same period the prior year.

Non-GAAP adjusted fully distributed net income for the fiscal second quarter of $88.4 million increased $18.4 million from $70.0 million for the same period a year ago. Non-GAAP adjusted fully distributed earnings per share totaled $0.66, compared with $0.50 for the same period a year ago. Adjusted fully distributed earnings per share is a non-GAAP financial measure that represents net income, adjusted for non-recurring and non-cash items, attributable to all stockholders as if all Class B stockholders exchanged their Class B common units and associated Class B common shares for Class A common shares.

Segment Results

Supply Chain Services
For the fiscal second quarter ended Dec. 31, 2018, Supply Chain Services segment net revenue of $327.0 million increased $2.1 million from $324.9 million a year ago. Net administrative fees revenue of $165.7 million increased by $6.4 million, or 4%, from the prior year primarily driven by further contract penetration of existing members and, to a lesser degree, the impact of conversion of new members. Net administrative fees in the fiscal 2019 second quarter under the previous revenue recognition standard totaled $169.8 million, an increase of 7% over a year ago, reflecting the impact of timing associated with certain cash collections between quarters.

Products revenue of $157.5 million decreased $4.6 million from $162.1 million a year ago. Growth in oncology and respiratory-related drug revenue was offset primarily by the impact of gross to net revenue recognition changes associated with the adoption of ASC 606, which negatively impacted revenue by $11.9 million, and to a lesser extent by reimbursement compression in the integrated pharmacy business.

Supply Chain Services segment non-GAAP adjusted EBITDA for the fiscal 2019 second quarter increased to $134.1 million from $132.0 million for the same period a year ago. Growth in net administrative fees revenue and decreased selling, general and administrative expenses were partially offset by reimbursement compression in the integrated pharmacy business and by increases in certain product-related costs in the direct sourcing business.

Performance Services
For the fiscal second quarter ended Dec. 31, 2018, Performance Services segment net revenue of $94.9 million increased $8.4 million from $86.5 million for the same quarter last year, driven by growth in applied sciences and analytics services as well as by growth in cost management consulting services. Under the new accounting standard, consulting services revenue is now recognized proportionally to when services are provided, and the company generally no longer is required to defer recognition until certain performance conditions are met.

Performance Services segment non-GAAP adjusted EBITDA totaled $37.1 million for the fiscal 2019 second quarter, a $9.2 million increase from $27.9 million for the same quarter last year. The increase was primarily the result of higher revenue partially offset by increases in selling, general and administrative expenses.

Results of Operations for the Six Months Ended Dec. 31, 2018
For the six months ended Dec. 31, 2018, GAAP net revenue increased to $823.4 million from net revenue of $802.0 million for the same period a year ago.

For the six-month period, GAAP net income totaled $186.8 million, compared with $80.4 million for the same period a year ago. Year-ago net income was impacted by a decrease in the effective tax rate due to federal tax reform, resulting in a re-measurement of tax receivable agreement liabilities totaling $177.2 million, offset by an increase in tax expense of $221.2 million attributable to the re-measurement of deferred tax balances. This resulted in income tax expense of $244.3 million in the year-ago quarter, compared with $12.6 million in the current quarter. Fiscal 2019 and 2018 six-month GAAP net income attributable to stockholders required non-cash adjustments of $(56.5) million and $638.3 million, respectively, to reflect changes in redemption value of the limited partners Class B common unit ownership at the end of each period. These non-cash adjustments result primarily from changes in the number of Class B common units outstanding and the company’s stock price between periods and do not reflect results of the company’s business operations. After these non-cash adjustments, the company reported net income attributable to stockholders of $12.6 million compared with $617.6 million a year ago. On a diluted per-share basis, net income totaled $0.22 compared with $0.36 for the same period a year ago. See "Calculation of GAAP Earnings per Share" in the income statement section of this press release.

For the six months ended Dec. 31, 2018, non-GAAP adjusted EBITDA of $280.6 million increased from $252.7 million for the same period last year. Non-GAAP adjusted fully distributed net income of $175.3 million increased from $131.7 million for the same period a year ago, while non-GAAP adjusted fully distributed earnings per share increased to $1.31 from $0.94.

Supply Chain Services segment net revenue for the first six months of fiscal 2019 increased to $642.8 million from $630.7 million a year earlier. Supply Chain Services segment adjusted EBITDA increased to $269.5 million from $257.7 million for the prior year.

Performance Services segment net revenue for the six months of fiscal 2019 increased to $180.6 million from $171.3 million a year earlier. Segment adjusted EBITDA increased to $67.7 million from $49.2 million.

Cash Flows and Liquidity

Net cash provided by operating activities was $212.3 million for the six-month period ended Dec. 31, 2018, compared with $206.5 million for the same period last year. The increase in cash flow from operations was primarily driven by increased net administrative fees and other services and support revenue and decreased cost of services revenue and selling, general and administrative expenses in the current period, partially offset by increased working capital needs. At Dec. 31, 2018, the company’s cash and cash equivalents totaled $110.6 million, compared with $152.4 million at June 30, 2018. At Dec. 31, 2018, the company had an outstanding balance of $100.0 million on its five-year, $1.0 billion revolving credit facility.

Non-GAAP free cash flow for the six-month period ended Dec. 31, 2018 was $116.6 million, compared with $122.2 million for the same period a year ago and was impacted by the $18.0 million TRA payment made to member owners in the current period. Timing of the payment shifted to July in the current year from June in previous years due to a change in the company’s federal tax filing deadline. The company expects free cash flow to exceed 50% of non-GAAP adjusted EBITDA for the full fiscal year. The company defines free cash flow as cash provided by operating activities less quarterly tax distributions and annual TRA payments to limited partners and purchases of property and equipment (see free cash flow reconciliation to net cash provided by operating activities in the tables section of this press release).

Through the close of trading on Dec. 31, 2018, the company repurchased approximately 2.9 million shares of Class A common stock for $109.5 million. The repurchases took place under the company’s ongoing $250.0 million stock repurchase program for fiscal 2019, and had the impact of adding approximately $0.01 to diluted per-share results for the period. The repurchase authorization may be expanded, suspended, delayed or discontinued at any time at the discretion of the Board of Directors.

Fiscal 2019 Outlook and Guidance

Based on results for the six months ended Dec. 31, 2018, management’s current expectations for the remainder of fiscal 2019 and the realization of previously disclosed underlying assumptions, the company reaffirms its full fiscal-year 2019 guidance ranges for consolidated net revenue, non-GAAP Supply Chain Services and Performance Services segment revenue, non-GAAP adjusted EBITDA and non-GAAP adjusted fully distributed earnings per share. Underlying assumptions have not changed with the exception of stock-based compensation expense, which is now estimated in a range of $29 million to $31 million.

* The company does not meaningfully reconcile guidance for non-GAAP adjusted EBITDA and non-GAAP adjusted fully distributed earnings per share to net income attributable to stockholders or earnings per share attributable to stockholders because the company cannot provide guidance for more significant reconciling items between net income attributable to stockholders and adjusted EBITDA and between earnings per share attributable to stockholders and non-GAAP adjusted fully distributed earnings per share without unreasonable effort. This is due to two primary reasons:

• Reasonable guidance cannot be provided for reconciling the adjustment of redeemable limited partners’ capital to redemption amount – historically the largest adjustment in the reconciliation from non-GAAP to GAAP amounts – due to the fact that the increase or decrease in this item is based on the change in the number of Class B common units outstanding and change in stock price between quarters, which the company cannot predict, control or reasonably estimate.

• Reasonable guidance cannot be provided for earnings per share attributable to stockholders because the ongoing quarterly member-owner exchange of Class B common units and corresponding Class B common stock into shares of Class A common stock impacts the number of shares of Class A common stock outstanding each quarter, which the company cannot predict, control or reasonably estimate. Member owners have the right, but not the obligation, to exchange class B common units on a quarterly basis, and the company has the discretion to settle any exchanged units for Class A common stock, cash, or a combination thereof, neither of which can be predicted, controlled or reasonably estimated at this time.

Conference Call

Premier management will host a conference call and live audio webcast on Tuesday, Feb. 5, 2019, at 8:00 a.m. ET, to discuss the company’s financial results. The conference call can be accessed through a link provided on the investor relations page on Premier’s website at investors.premierinc.com. Those wanting to participate by phone may do so by dialing 844.296.7719 and providing the operator with conference ID number: 6890785. International callers should dial 574.990.1041 and provide the same passcode. The company encourages callers to dial in at least five minutes before the start of the call to register. The archived webcast will be accessible on Premier’s investor relations page.

On February 5, 2019 NanOlogy, a clinical-stage oncology company, reported its Chief Medical Officer, Gere diZerega, MD, will participate on an immuno-oncology panel at the BIO CEO and Investor Conference February 11, 2019 9:00-9:55 am, Schubert Complex, 6th floor, New York Marriot Marquis (Press release, NanOlogy, FEB 5, 2019, View Source [SID1234533072]).

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The panel, entitled "Reshaping Tumor Microenvironments via Immunotherapies," will examine the next wave of innovation in immunotherapies for leveraging knowledge of how tumor microenvironments develop to create treatments able to demonstrate more durable effects on shrinking tumors across wider ranges of patients.

Based on a proprietary production technology platform, NanOlogy is developing patented submicron particle forms of paclitaxel and docetaxel designed for local delivery directly to the disease site. Preclinical and clinical data across broad therapeutic areas, including genitourinary, gastrointestinal, peritoneal, and lung cancers indicate targeted delivery of the submicron particles of pure drug enhance tumor kill and generate significant immune stimulation with minimal systemic side effects. The data underscore the potential for NanOlogy investigational drugs to be ideal companions to IO therapy for certain solid tumors.

The company is in clinical development of its investigational drugs for prostate cancer, bladder cancer, renal cancer, peritoneal/ovarian cancers, pancreatic cancer, pancreatic mucinous cysts, and lung cancer.

BioSpace recently named NanOlogy to its list of Top 20 Life Sciences companies to watch in 2019.

Joining Dr. diZerega on the panel are: Moderator: Jotin Marango, MD, PhD, Managing Director, Senior Research Analyst, ROTH Capitol; Lewis H. Bender, Chief Executive Officer, Intensity Therapeutics; Sabine Chlosta, MD, PhD, Chief Medical Officer, Triumvira Therapeutics; and Eric Falcand, Vice President of Business Development & Licensing, Servier.

NanOlogy investigational drugs are progressing under the FDA streamlined 505(b) (2) regulatory pathway. The NanOlogy submicron particle technology platform is based on a patented production process that reduces the size of paclitaxel and docetaxel API crystals by up to 400 times into stable submicron particles of pure drug with exponentially increased surface area and unique geometry. The submicron particles are so unique that they are protected under a composition of matter patent (US 9,814,685) valid until 2036, which provides new molecular entity-like advantages without the risks and timeline associated with NME drug development.

On February 5, 2019 OPKO Health, Inc. ("OPKO Health" or the "Company") (NASDAQ: OPK) reported the pricing of its offering of $200 million aggregate principal amount of Convertible Senior Notes due 2025 (the "Notes") (Press release, Opko Health, FEB 5, 2019, View Source [SID1234533071]). The Notes will be general senior unsecured obligations of the Company, will pay interest semiannually in arrears at a rate of 4.50% per annum, and will mature on February 15, 2025, unless earlier repurchased, redeemed or converted. The Notes will be convertible into, at the Company’s election, cash, shares of the Company’s common stock, or a combination of cash and common stock, as further described in the prospectus supplement. The conversion rate for the Notes will initially be 236.7424 shares of common stock per $1,000 principal amount of the Notes, which is equivalent to an initial conversion price of approximately $4.22 per share of common stock, and is subject to adjustment under the terms of the Notes. The Company has granted the underwriter an option to purchase up to an additional $30 million aggregate principal amount of the Notes to cover over-allotments, if any. The sale of the Notes is expected to close on February 7, 2019.

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The Company may not redeem the Notes prior to February 15, 2022, but may redeem the Notes, at its option, on or after February 15, 2022 if the last reported sale price of the Company’s common stock has been at least 130% of the conversion price for the Notes for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which the Company provides notice of redemption. The redemption price will equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

The Company intends to use the net proceeds received from the offering of the Notes to fund research and development to further develop and commercialize its portfolio of proprietary pharmaceutical and diagnostic products and for working capital, capital expenditures, acquisitions and other general corporate purposes, which will include the repayment or repurchase of indebtedness or debt securities outstanding from time to time, including $28.8 million principal amount and accrued but unpaid interest currently outstanding under the Company’s line of credit with an affiliate of the Company’s Chairman and Chief Executive Officer.

In connection with the Company’s offering of the Notes, the Company has entered into a share lending agreement with an affiliate of Jefferies LLC (the "Share Borrower"), under which it will lend to the Share Borrower a total of up to 30 million shares of the Company’s common stock. The borrowed shares will be newly-issued shares issued in connection with the offering of the Notes and will be cancelled or held as treasury shares upon the expiration or early termination of the share lending agreement.

Purchasers of the Notes may separately sell up to 30 million shares of the Company’s common stock that they may borrow through the Share Borrower. The Company expects that the selling stockholders will use the short position created by such sales to establish their initial hedge with respect to their investments in the Notes. The Company will not receive any proceeds from the sale of the borrowed shares.

Jefferies LLC is acting the sole book-running manager for the offering.

The offering of the Notes and the offering of the Company’s common stock is being made by means of separate prospectus supplements to the prospectus forming a part of the Company’s effective shelf registration statement filed with the Securities and Exchange Commission (the "SEC") on January 28, 2019 and other related documents. You may obtain these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the preliminary prospectus supplements may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY, 10022, by email at [email protected] or by phone at +1 877 821 7388. Before you invest, you should read the prospectus supplements and accompanying base prospectus along with other documents that the Company has filed with the SEC for more complete information about the Company and these offerings.

This press release shall not constitute an offer to sell, or a solicitation of an offer to buy, the Notes, the Company’s common stock or any other securities, nor will there be any sale of convertible notes, the Company’s common stock or any other securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

On February 5, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) ("Actinium" or "the Company") reported that its novel Phase 1/2 combination trial of Actimab-A and venetoclax has been initiated (Press release, Actinium Pharmaceuticals, FEB 5, 2019, View Source [SID1234533070]). Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center will serve as Principal Investigator for this study. The Phase 1/2 combination trial will enroll patients with relapsed or refractory AML or Acute Myeloid Leukemia that have been previously treated with venetoclax and patients that have never received venetoclax.

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Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie and Genentech. BCL-2 is one of several proteins encoded by the BCL2 gene family, which regulates apoptosis or programmed cell death. MCL-1 is another protein encoded by the BCL2 gene family that is also overexpressed in cancers, including relapsed or refractory AML, that prevents apoptosis and promotes resistance to venetoclax, which does not bind to MCL-1. It has been demonstrated that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium believes that the targeted radiation from Actimab-A can more effectively deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. In preclinical studies, Actinium demonstrated this synergistic effect when combining Actimab-A with venetoclax that led to increased cancer cell death, the results of which were highlighted in a webinar hosted by Actinium that can be accessed here.

Dr. Dale Ludwig, Actinium’s Chief Scientific Officer said, "The ability to deplete MCL-1, a known resistance mechanism to venetoclax, by selectively targeting AML cells that express CD33 with Actimab-A and hitting them with potent alpha radiation from Actinium-225 is very compelling. I am excited to see this study enter the clinic as I believe Actimab-A’s targeted radiation will prove to be synergistic with venetoclax as we have shown in our preclinical work. With our powerful Antibody Warhead Enabling technology platform we are excited to deploy targeted radiation as a weapon against cancer cells by exploiting their susceptibility to radiation and leveraging potential synergies with other therapeutic modalities."

Dr. Mark Berger, Chief Medical Officer of Actinium said’ "Despite advancements and recent approvals of AML therapies including venetoclax, there is a real need to improve their incremental benefits and produce more durable responses as well as curative outcomes for patients with relapsed and refractory disease. We are excited about this trial as our recent phase 2 study with Actimab-A demonstrated an ability to produce complete responses in difficult to treat AML patients. We attribute this efficacy to ARCs being agnostic to cytogenetic factors, the ubiquitous expression of CD33 in AML and potency of the Actinium-225 warhead. We are hopeful that the combination of Actimab-A and venetoclax will in the clinic will validate our preclinical studies showing synergy and result in improved patient outcomes."

On February 5, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported completing the submission of a supplemental Biologics License Application to the U.S. Food and Drug Administration (FDA) for Kadcyla (ado-trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (EBC) with residual disease after neoadjuvant (before surgery) treatment (Press release, Genentech, FEB 5, 2019, View Source [SID1234533069]). The FDA is reviewing the application under the Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.

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"Kadcyla was granted Breakthrough Therapy Designation and is also the first Genentech medicine to be reviewed under the FDA’s Real-Time Oncology Review pilot program; both FDA initiatives aim to expedite reviews and bring medicines to patients sooner," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We are working closely with the FDA to bring Kadcyla to people with HER2-positive early breast cancer who have residual disease after neoadjuvant therapy as early as possible."

This application is based on results of the Phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50 percent (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin (trastuzumab) as an adjuvant treatment in people with HER2-positive EBC who have residual disease present following neoadjuvant treatment. People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease. At three years, 88.3 percent of people treated with Kadcyla did not have their breast cancer return compared to 77.0 percent treated with Herceptin, an absolute improvement of 11.3 percent.

The most common Grade 3-4 side effects (≥1 percent) with Kadcyla in the KATHERINE study were decreased platelet count; high blood pressure; radiation-induced skin injury; numbness, tingling or pain in the hands or feet; decreased neutrophil count; low blood potassium level; fatigue and decrease in red blood cells.

About the KATHERINE study

KATHERINE is an international, multi-center, two-arm, randomized, open-label, Phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive EBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomization free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include disease-free survival and overall survival.

About HER2-positive breast cancer

Breast cancer is the most common cancer among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20 percent of breast cancers are HER2-positive based on the result of a diagnostic test.

About Kadcyla

Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cells. It is designed to limit damage to healthy tissues, although it can still affect them. Kadcyla can cause serious side effects. It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved for the treatment of HER2-positive metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Kadcyla Indication Statement

Kadcyla, as a single agent, is indicated for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:

Received prior therapy for metastatic disease, or
Developed disease recurrence during or within six months of completing adjuvant therapy.
Important Safety Information

Most important safety information about Kadcyla

Kadcyla is not the same medicine as trastuzumab (Herceptin).

Liver problems

Kadcyla may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), stomach pain, dark urine or itching.
Heart problems

Kadcyla may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, rapid weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness, or irregular heartbeat.
Pregnancy

Receiving Kadcyla during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while receiving Kadcyla and for seven months after a patient’s last dose of Kadcyla.
If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
If a patient is exposed to Kadcyla during pregnancy, or becomes pregnant within seven months following her last dose of Kadcyla, she is encouraged to report Kadcyla exposure to Genentech at (888) 835-2555.
If a male patient has a female partner that could become pregnant, birth control should be used during treatment and for four months following his last dose of Kadcyla.
A patient should not breastfeed during treatment and for seven months after the last dose of Kadcyla.
A patient should contact their doctor right away if they experience symptoms associated with these side effects.

Additional possible serious side effects of Kadcyla

Lung problems

Kadcyla may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness and fluid in the lungs.
Infusion-related reactions

Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways or a fast heartbeat. A patient’s doctor will monitor the patient for infusion-related reactions.
Serious bleeding

Kadcyla can cause life-threatening bleeding. Taking Kadcyla with other medications used to thin the blood (antiplatelet) or prevent blood clots (anticoagulation) can increase the risk of bleeding. A patient’s doctor should provide additional monitoring if the patient is taking one of these other drugs while on Kadcyla. Life-threatening bleeding may also happen with Kadcyla, even when blood thinners are not also being taken.
Low platelet count

Low platelet count may happen during treatment with Kadcyla. Platelets help the blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms.
Nerve damage

Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, muscle weakness, or loss of muscle function.
Skin reactions around the infusion site

Kadcyla may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion.
HER2 testing and Kadcyla

A patient must have a HER2 test to determine if their breast cancer is HER2-positive before taking Kadcyla, because benefit has been shown only in patients whose tumors are HER2-positive.

Most common side effects of Kadcyla

The most common side effects seen in people taking Kadcyla are:

Tiredness
Nausea
Pain that affects the bones, muscles, ligaments and tendons
Bleeding
Low platelet count
Headache
Liver problems
Constipation
Nosebleeds
Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.