On July 26, 2016 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported that it has received a $50 million milestone payment from its worldwide collaboration partner, Valeant Pharmaceuticals International, Inc. (NYSE:VRX), resulting from the US Food and Drug Administration’s marketing approval last week of RELISTOR Tablets for the treatment of opioid-induced constipation in adults with chronic non-cancer pain (Press release, Progenics Pharmaceuticals, JUL 26, 2016, View Source [SID:1234514031]).

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"We are pleased that our partner Valeant can now offer RELISTOR in a more convenient tablet form to patients in need," said Mark Baker, Chief Executive Officer of Progenics. "This and other sales milestone payments that we may receive from sales of RELISTOR provide an important source of non-dilutive financing for our Company as we approach topline, registrational data on AZEDRA and advance our diverse pipeline of prostate cancer imaging agents and therapeutics."

Under a 2011 collaboration with Salix Pharmaceuticals, Inc. (acquired by Valeant in April 2015), Progenics is also entitled to receive up to $200 million of sales milestone payments based on specified U.S. sales targets. The sales milestone payments range from $10 million when calendar-year U.S. net sales first exceed $100 million, to $75 million when such sales first exceed $1 billion. Each sales milestone payment is payable one time only, and one or more, or all, sales milestones could become payable within the same calendar year if the specified sales levels are met. Progenics also earns tiered royalties on total RELISTOR U.S. net sales, as follows: 15% on U.S. net sales up to $100 million, 17% on the next $400 million in U.S. net sales, and 19% on U.S. net sales over $500 million. Outside of the U.S. Progenics is entitled to receive 60% of any up-front milestone, royalty and other revenue, net of certain costs, as specified in our license agreement with Valeant.

About RELISTOR

Progenics has exclusively licensed development and commercialization rights for its first commercial product, RELISTOR, to Valeant. RELISTOR Tablets (450 mg once daily) is approved in the United States for the treatment of OIC in patients with chronic non-cancer pain. RELISTOR Subcutaneous Injection (12 mg and 8 mg) is a treatment for opioid-induced constipation approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.

Important Safety Information about RELISTOR

RELISTOR (methylnaltrexone bromide) Tablets is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR.

Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

The most common adverse reactions (≥ 12%) in adult patients with opioid-induced constipation and chronic non-cancer pain receiving RELISTOR tablets were abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

Please see complete Prescribing Information for RELISTOR at valeant.com. For more information about RELISTOR, please visit www.relistor.com.

On July 26, 2016 BIND Therapeutics, Inc. (NASDAQ: BIND), a biotechnology company developing targeted and programmable therapeutics called ACCURINS, reported that Pfizer Inc. (NYSE: PFE) prevailed at a Section 363 auction to purchase substantially all of BIND’s assets (Press release, BIND Therapeutics, JUL 26, 2016, View Source [SID1234556287]). The winning bid of $40 million, subject to U.S. Bankruptcy Court approval for which a hearing is scheduled to take place on July 27, 2016, was selected as the highest and best bid. NanoCarrier Co., Ltd. has been selected as the back-up bidder. The Company plans to disclose additional terms of its agreement with Pfizer upon Court approval.

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BIND initiated voluntary Chapter 11 bankruptcy protection on May 1, 2016 and conducted a sale of assets, pursuant to Section 363 of the Bankruptcy Code, during an auction held on July 25 and 26, 2016.

On July 26, 2016 RedHill Biopharma Ltd. (NASDAQ:RDHL) (TASE:RDHL) ("RedHill" or the "Company"), a biopharmaceutical company primarily focused on development and commercialization of late clinical-stage, proprietary, orally-administered, small molecule drugs for inflammatory and gastrointestinal diseases and cancer, reported its financial results for the quarter ended June 30, 2016 (Press release, RedHill Biopharma, JUL 26, 2016, View Source [SID:1234514032]).

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The Company will host a conference call on Tuesday, July 26, 2016, at 9:00 am EDT to review the financial results and business highlights, dial-in details are included below.

Financial highlights for the quarter ended June 30, 20161:

Research and Development Expenses for the second quarter of 2016 were $6.0 million, an increase of $0.9 million, compared to $5.1 million in the second quarter of 2015. Research and Development Expenses for the six months ended June 30, 2016 were $10.7 million, an increase of $1.8 million, compared to $8.9 million in the comparable period of 2015. The increase in 2016 resulted primarily from clinical trial costs related to the ongoing Phase III MAP US study with RHB-104 (Crohn’s disease) and from preparations for several Phase I/II studies with YELIVA for multiple oncology, inflammatory and gastrointestinal indications.

General, Administrative and Business Development Expenses in the second quarter of 2016 were $1.2 million, an increase of $0.4 million, compared to $0.8 million in the second quarter of 2015. General, Administrative and Business Development Expenses for the six months ended June 30, 2016 were $2.4 million, an increase of $0.7 million, compared to $1.7 million in the comparable period of 2015. The increase was mainly due to enhanced business development activities.

Operating Loss in the second quarter of 2016 was $7.2 million, an increase of $1.3 million, compared to $5.9 million in the second quarter of 2015. Operating Loss for the six months ended June 30, 2016 were $13.1 million, an increase of $2.5 million, compared to $10.6 million in the comparable period of 2015. The increase was mainly due to increases in Research and Development Expenses, as detailed above.

Net Cash Used in Operating Activities in the second quarter of 2016 was $5.7 million, an increase of $1.0 million, compared to $4.7 million in the second quarter of 2015. Net Cash Used in Operating Activities for the six months ended June 30, 2016 was $10.7 million, an increase of $2.6 million, compared to $8.1 million in the comparable period of 2015. The increase mainly reflects the increase in Operating Loss, as detailed above.

Net Cash Used in Investment Activities in the second quarter of 2016 was $2.9 million, compared to Net Cashed Provided by Investment Activities of $3.5 million in the second quarter of 2015. Net Cash Used in Investment Activities for the six months ended June 30, 2016 was $7.5 million, an increase of $3.9 million, compared to $3.6 million in the comparable period of 2015. The increase in Net Cash Used in Investment Activities was mainly due to an increase in bank deposits and marketable securities in 2016.

Net Cash Provided by Financing Activities in the second quarter of 2016 was $0.1 million, compared to an immaterial amount in the second quarter of 2015. Net Cash Provided by Financing Activities for the six months ended June 30, 2016 was $0.1 million, compared to $13.2 million in the comparable period of 2015, which resulted mainly from the Company’s public offering in February 2015.

Cash Balance2 as of June 30, 2016 was $47.7 million, a decrease of $10.4 million, compared to $58.4 million as of December 31, 2015. The decrease was a result of the ongoing operations, mainly related to research and development activities.

"We have achieved several significant clinical and operational milestones this quarter, while continuing to maintain our financial discipline," said Mr. Micha Ben Chorin, RedHill’s CFO. "With a strong cash position of $47.7 million at the end of the second quarter we are well-positioned to advance our strategic and operational plans, including the establishment of commercial operations in the U.S. During the second quarter, we continued to actively advance our three Phase III-stage gastrointestinal programs. We are working towards several anticipated milestones, including interim DSMB analysis of the RHB-104 Phase III study for Crohn’s disease, final results from the Phase IIa study with RHB-104 for multiple sclerosis, initiation of a confirmatory Phase III study with RHB-105 for the treatment of H. pylori infection and top-line results from the BEKINDA Phase III study for gastroenteritis. In the coming weeks, we expect to provide a mid-year business update that will highlight the status and timelines for RedHill’s main operations."

Conference Call and Webcast Information:

The Company will host a conference call on Tuesday, July 26, 2016, at 9:00 am EDT to review the financial results and business highlights.

To participate in the conference call, please dial the following numbers 5-10 minutes prior to the start of the call: United States: +1-877-280-1254; International: +1-646-254-3388; and Israel: +972-3-763-0147. The access code for the call is 539724.

The conference call will be broadcasted live and available for replay on the Company’s website, View Source, for 30 days. Please access the Company’s website at least 15 minutes ahead of the conference to register, download, and install any necessary audio software.

Recent operational highlights:

On April 11, 2016, RedHill announced that it had initiated a randomized, double-blind, placebo-controlled, 2-arm parallel group Phase II clinical study in the U.S. evaluating the safety and efficacy of BEKINDA 12 mg in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). The study is expected to be conducted in 12 clinical sites in the U.S. and to enroll 120 patients who will be randomized 60:40 to receive either BEKINDA 12 mg or a placebo, once daily, for a period of eight weeks. The primary endpoint for the study is the proportion of patients in each treatment group with response in stool consistency as compared to baseline, per U.S. Food and Drug Administration (FDA) guidance definition. Secondary endpoints include the proportion of patients in each treatment group who are pain responders and the proportion of patients in each treatment group who are responders to the combined endpoints of stool consistency and pain, per FDA guidance definition. RedHill further announced, on June 20, 2016, that the first patients in the Phase II study had been dosed.

On April 18, 2016, RedHill announced that it had concluded a positive Type B Meeting with the FDA regarding the path to marketing approval of RHB-105 and the planned confirmatory Phase III study for the treatment of H. pylori infection. The FDA confirmed, subject to final minutes of the meeting, the planned two-arm, randomized, double-blind, active comparator design of the confirmatory Phase III study. Based on FDA feedback, and subject to successful completion, the planned confirmatory Phase III study, along with the successfully completed first Phase III study and data from a supportive PK program, are expected to support a U.S. New Drug Application (NDA) for RHB-105.

The FDA Type B meeting announcement followed the successful final results from the first Phase III clinical study with RHB-105 (the ERADICATE Hp study) reported in March 2016, confirming that the ERADICATE Hp study successfully met its primary endpoint of superiority over historical standard-of-care (SoC) eradication rate levels of 70%, with high statistical significance (p < 0.001). The results demonstrated 89.4% efficacy in eradicating H. pylori infection with RHB-105. RHB-105 has been granted Qualifying Infectious Disease Product (QIDP) designation by the FDA, providing a Fast-Track development pathway, as well as Priority Review status, potentially leading to a shorter review time by the FDA of a NDA, if filed. If approved, RHB-105 will have a total of 8 years of market exclusivity.

On May 4, 2016, RedHill announced that the U.S. National Cancer Institute (NCI) has awarded the Medical University of South Carolina (MUSC) a $1.8 million grant to support a broad range of studies on the feasibility of targeting sphingolipid metabolism for the treatment of a variety of solid tumor cancers. One component of the studies includes a planned Phase II study with YELIVA (ABC294640) for the treatment of advanced hepatocellular carcinoma (HCC), the most common primary malignant cancer of the liver3. The Phase II study, planned to be initiated in the third quarter of 2016, will be conducted at MUSC and additional clinical sites and is intended to evaluate the efficacy and safety of YELIVA as a second-line monotherapy in patients with advanced HCC. The NCI grant covers a five-year period. The Phase II HCC study will be further supported by additional funding from RedHill, which acquired the exclusive worldwide rights to YELIVA from Apogee Biotechnology Corp. (Apogee).

On June 21, 2016, RedHill announced positive final results from the Phase I study with YELIVA in advanced solid tumors. The results confirmed that the study successfully met both its primary and secondary endpoints, demonstrating that YELIVA can be safely administered to cancer patients at doses that provide circulating drug levels that are predicted to have therapeutic activity, based on levels required in preclinical models. The study included the first-ever longitudinal analyses of plasma S1P levels as a potential pharmacodynamic biomarker for activity of a sphingolipid-targeted drug. Administration of YELIVA resulted in a rapid and pronounced decrease in S1P levels over the first 12 hours, with return to baseline at 24 hours, which is consistent with clearance of the drug. YELIVA was well tolerated over a prolonged period at doses inducing the expected pharmacodynamic effects.

On June 22, 2016, RedHill announced the publication of an article4 demonstrating that the triple combination of the RHB-104 active components provides excellent synergistic activity in the inhibition of mycobacterial growth, potentially leading to a new and effective treatment for Crohn’s disease associated with Mycobacterium avium subspecies paratuberculosis (MAP) infection. The article, entitled "RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis" describes a pre-clinical study intended to determine the efficacy of the RHB-104 active components (the antibiotics clarithromycin, clofazimine and rifabutin) against MAP strains isolated from the blood, tissue and milk of Crohn’s disease patients. The results of the study demonstrated that the RHB-104 active components, in their individual concentrations or in dual combinations, were not as effective against all microorganisms, compared to the triple combination at minimum inhibitory concentrations level.

On July 5, 2016, RedHill and its co-development partner, IntelGenx Corp. (IntelGenx), announced the signing of an exclusive license agreement with Grupo JUSTE S.A.Q.F (Grupo JUSTE), for the commercialization of RIZAPORT oral thin-film for acute migraines. Under the terms of the agreement, RedHill granted Grupo JUSTE the exclusive rights to register and commercialize RIZAPORT in Spain and a right of first refusal for a predefined term for the territories of Belize, Carribean, Chile, Colombia, Costa Rica, Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, the Middle East and Morocco. RedHill and IntelGenx are entitled to receive an upfront payment and additional milestone payments upon the achievement of certain predefined regulatory and commercial targets, as well as tiered royalties. Financial terms of the agreement were not disclosed. The initial term of the agreement is for ten years from the date of the first commercial sale and shall automatically renew for an additional two-year term. Commercial launch in Spain is expected to take place in the second half of 2017.

On July 13, 2016, RedHill announced the signing of a research collaboration agreement with the U.S. National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), intended to evaluate RedHill’s proprietary experimental therapy for the treatment of Ebola virus disease. The new research collaboration follows encouraging results from preliminary non-clinical studies conducted in conjunction with the NIAID using RedHill’s proprietary experimental therapy. If successful, this study is intended to provide supportive data for discussions with the FDA for potential use of the Animal Rule pathway for approval. Ebola virus disease is a severe and often fatal illness, which can cause severe hemorrhagic fever in humans and has a mortality rate ranging from 25% to 90%5. There is currently no FDA approved treatment for Ebola virus disease.

On July 21, 2016, RedHill announced that it had received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a new patent covering RHB-105. The patent application, entitled "Pharmaceutical Compositions For The Treatment Of Helicobacter Pylori" expands RedHill’s patent portfolio covering RHB-105 and is expected to be valid until 2034, once granted. The Company is currently prosecuting additional U.S. and international patent applications covering RHB-105.

On July 26, 2016 Baxter International Inc. (NYSE:BAX) reported results for the second quarter of 2016, and increased its sales and earnings per share outlook for full-year 2016. Baxter’s second quarter worldwide sales totaled $2.6 billion, an increase of 4 percent on a reported basis and 6 percent on a constant currency basis as compared to the prior-year period (Press release, Baxter, JUL 26, 2016, View Source [SID:1234514034]).

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"Our second quarter results reflect the steady progress we are making on our strategy to drive industry-leading performance through a disciplined focus on portfolio management and innovation, operational excellence and capital allocation," said José (Joe) E. Almeida, chairman and chief executive officer.

Financial Results

During the quarter, Baxter reported income from continuing operations of $1.2 billion, or $2.19 per diluted share, on a GAAP (Generally Accepted Accounting Principles) basis. These results included an after-tax net gain of approximately $1.1 billion from the disposition of the company’s remaining shares of Baxalta Incorporated (Baxalta), which the company spun-off in July 2015. Partially offsetting these results were net after-tax special items totaling $192 million primarily related to business optimization initiatives, intangible asset amortization, asset impairment and Baxalta related spin-off costs.

On an adjusted basis, excluding special items, Baxter’s second quarter income from continuing operations totaled $256 million, or $0.46 per diluted share, exceeding the company’s previously-issued guidance of $0.38 to $0.40 per diluted share.

Baxter’s second quarter worldwide sales totaled $2.6 billion, an increase of 4 percent on a reported basis and 6 percent on a constant currency basis as compared to the prior-year period. Sales within the United States were $1.1 billion, advancing 10 percent, while international sales totaled $1.5 billion, representing a 1 percent increase on a reported basis, and an increase of 3 percent on a constant currency basis. Adjusting for the impact of foreign exchange and a generic market entrant in the United States for the company’s oncology injectable, cyclophosphamide, Baxter’s sales increased 12 percent in the U.S. and globally rose 7 percent in the second quarter.

By business, Hospital Products sales of $1.6 billion increased 6 percent on a reported basis and 7 percent on a constant currency basis. Adjusting for the impact of foreign exchange and U.S. cyclophosphamide, Hospital Products sales advanced 9 percent from the prior year period. Hospital Products performance in the quarter benefited from strong sales across the portfolio, particularly within its U.S. Fluid Systems franchise, driven by solid demand for Baxter’s next-generation SIGMA SPECTRUM infusion pump as well as favorable demand and pricing for IV solutions. Strength internationally in anesthesia products and hospital pharmacy compounding services also contributed to growth in the quarter.

Baxter’s Renal sales totaled $965 million, representing a 2 percent increase on a reported basis, and a 4 percent increase on a constant currency basis. Increased demand globally for continuous renal replacement therapies along with strong sales of peritoneal dialysis products contributed to growth in the quarter. Baxter’s new AMIA Automated Peritoneal Dialysis (APD) System with the SHARESOURCE Connectivity Platform, which was launched in the U.S. in late 2015 and was recently approved by Health Canada, is contributing to growth with more than 500 patients now being treated with AMIA in the U.S. The AMIA APD and SHARESOURCE system is the first APD device cleared in the United States and Canada to include patient-centric features such as voice guidance, a touchscreen control panel and two-way telemedicine capabilities for remote patient management.

During the second quarter, Baxter also completed the disposition of its retained stake in Baxalta, which included an equity contribution of approximately $700 million to the company’s U.S. pension plan. It also included completion of an equity-for-equity share exchange which resulted in a reduction of Baxter’s outstanding share count of approximately 11 million.

"The successful disposition of the retained equity stake in Baxalta allowed us to effectively restructure our balance sheet and provides us with significant flexibility to invest in both organic and inorganic growth initiatives while also returning value to shareholders through dividends and stock repurchases," said Jay Saccaro, Baxter’s chief financial officer.

Financial Outlook

Based on the company’s strong performance in the first six months of the year, Baxter is raising its financial outlook for full-year 2016. For full-year 2016, Baxter now expects reported sales growth of 1 percent to 2 percent and on a constant currency basis, sales growth of 3 percent to 4 percent. In addition, the company now expects earnings from continuing operations, before special items, of $1.69 to $1.74 per diluted share for the full year as compared to previous guidance of $1.59 to $1.67 per diluted share.

For the third quarter, the company expects reported sales growth of 2 percent to 3 percent and on a constant currency basis, sales growth of 3 percent to 4 percent. Baxter expects earnings from continuing operations, before special items, of $0.43 to $0.45 per diluted share for the third quarter of 2016.

The earnings guidance for the third quarter and full-year 2016 excludes $0.05 and $0.22, respectively, per diluted share of intangible asset amortization expense; an estimated $0.02 and $0.08, respectively, per diluted share of Baxalta separation-related expense activities; an estimated $0.09 to $0.11 and $0.38 to $0.40, respectively, per diluted share of business optimization charges; and $7.88 per diluted share of asset impairment, debt extinguishment loss, product related reserve adjustments, and Baxalta retained stake gains for full-year 2016. These estimates are based on information reasonably available at the time of this release and future events or new information may result in different actual results. Reconciling for the inclusion of these items results in GAAP earnings of $0.25 to $0.29 per diluted share for the third quarter of 2016, and $8.87 to $8.94 per diluted share for full-year 2016.

On July 25, 2016 Janssen Research & Development, LLC reported that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation to the immunotherapy daratumumab (DARZALEX) in combination with lenalidomide (an immunomodulatory agent) and dexamethasone, or bortezomib (a proteasome inhibitor [PI]) and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy (Press release, Johnson & Johnson, JUL 25, 2016, View Source [SID:1234514044]). This marks the second time daratumumab has received a Breakthrough Therapy Designation, which is intended to expedite the development and review timelines of potential new medicines to treat serious or life-threatening diseases, where preliminary clinical evidence shows that the medicine may provide substantial improvement over existing therapies. 1 Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.2,3

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"Despite tremendous progress in the past 15 years, multiple myeloma remains a highly complex and difficult disease to treat, with most patients relapsing or becoming resistant to therapy," said MMY3003 (POLLUX) lead study author Meletios A. Dimopoulos, M.D., Department of Clinical Therapeutics, National and Kapodistrian 2 University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece. "Daratumumab has already shown pronounced activity as a monotherapy in heavily pre-treated patients. This designation underscores the potential of daratumumab in combination with either a proteasome inhibitor or an immunomodulatory agent to provide much-needed benefit to patients with at least one prior therapy."

Breakthrough Therapy Designation was granted to daratumumab based on data from two Phase 3 studies:

The MMY3004 (CASTOR) clinical trial evaluating daratumumab in combination with bortezomib and dexamethasone, compared to bortezomib and dexamethasone alone, in patients with multiple myeloma who received at least one prior therapy. Overall, the daratumumab combination therapy demonstrated a reduction in the risk of disease progression or death.
o These results were presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2016. More information can be found at www.ClinicalTrials.gov (NCT02136134).

The MMY3003 (POLLUX) clinical trial evaluating daratumumab in combination with lenalidomide and dexamethasone, compared to lenalidomide and dexamethasone alone, in patients with multiple myeloma who received at least one prior therapy. Overall, the addition of daratumumab reduced the risk of disease progression or death in these patients.
o These results were presented at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2016. More information can be found at www.ClinicalTrials.gov (NCT02076009).

"We are pleased that the FDA has granted a second Breakthrough Therapy Designation to daratumumab. This is an important recognition of the transformative potential of daratumumab and its possible benefit as a backbone therapy in combination with two of the most widely used regimens for multiple myeloma," said Craig L. Tendler, M.D., Vice President, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care, Janssen Research & Development, LLC. "We look forward to working closely with the FDA throughout the review process and remain committed to exploring the full clinical benefit of this promising compound for multiple myeloma patients who are eagerly awaiting new treatment options."

In November 2015, daratumumab (DARZALEX) was approved by the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.4

In May 2013, daratumumab received Breakthrough Therapy Designation from the FDA for this indication. 3 In May 2016, the European Commission (EC) granted conditional approval to DARZALEX for monotherapy of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.

About DARZALEX (daratumumab)

DARZALEX (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world.4 CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage. 5 Daratumumab is believed to induce tumor cell death through multiple immunemediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.4 Daratumumab is also believed to induce tumor cell death through immunomodulatory effects, according to a study recently presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper).6 DARZALEX is being evaluated in a comprehensive clinical development program that includes five Phase 3 studies across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases in which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor indication. DARZALEX was the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.4

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX. DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc. For more information, visit www.DARZALEX.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow.7,8 Refractory cancer occurs when a patient’s disease is resistant to treatment or in the case of multiple myeloma, patients progress within 60 days of their last therapy.9,10 Relapsed cancer means the disease has returned after a period of initial, partial or complete remission.7,11 Accounting for approximately one percent of all cancers and 15 percent to 20 percent of haematologic malignancies worldwide, multiple myeloma is designated as an orphan disease in both the U.S. and Europe. 11 Globally, it is estimated that 124,225 people were diagnosed, and 87,084 died from the disease in 2015. 12,13 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections.14 Patients who relapse after treatment with standard therapies (including PIs or immunomodulatory agents) typically have poor prognoses and few remaining options.3

DARZALEX (daratumumab) Important Safety Information – Professional 4

CONTRAINDICATIONS – None

WARNINGS AND PRECAUTIONS
Infusion Reactions – DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension. Signs and symptoms may include respiratory symptoms, such as cough, wheezing, larynx and throat tightness and irritation, laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis. Less common symptoms were hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions. Patients with a history of obstructive pulmonary disorders may require additional postinfusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with obstructive pulmonary disorders.

Interference with Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Interference with Determination of Complete Response – Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Adverse Reactions – The most frequently reported adverse reactions (incidence ≥20%) were: infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper respiratory tract infection (20%). 5 Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS – No drug interaction studies have been performed