On March 19, 2019 Novavax, Inc., (Nasdaq: NVAX) reported its financial results and operational highlights for the fourth quarter and twelve months ended December 31, 2018 (Press release, Novavax, MAR 19, 2019, View Source [SID1234534516]).

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"In 2018, we committed to focus on our two lead programs, ResVax and Nanoflu, and reflecting on last year’s activities, I am proud to say we have achieved significant results for both," said Stanley C. Erck, President and CEO of Novavax, Inc. "Although we were disappointed to miss the primary endpoint of our Prepare trial, ResVax is the first RSV vaccine to demonstrate efficacy for the prevention of RSV disease in a Phase 3 clinical trial. In addition, the successful Phase 2 results for our NanoFlu vaccine provide an opportunity to now confirm with the FDA the use of accelerated approval for licensure. We are now prepared to make meaningful advances on these programs during 2019."

Fourth Quarter 2018 and Subsequent Operational Highlights

ResVax Program

·In February 2019, Novavax announced top-line data from the Prepare trial, which was initiated in December 2015 to determine the efficacy of ResVax against medically significant RSV-positive lower respiratory tract infection (LRTI) in infants. Although the Prepare trial results did not meet the pre-specified primary efficacy endpoint, they demonstrate efficacy against a secondary objective (RSV LRTI hospitalizations). In addition, other pre-specified exploratory endpoints and post-hoc analyses highlight ResVax’ potential to improve global health against serious RSV disease.

NanoFlu Program

·In January 2019, Novavax announced positive top-line results of its Phase 2 clinical trial of NanoFlu comparing various quadrivalent formulations, with or without Novavax’ Matrix-M adjuvant, with two U.S.-licensed influenza vaccines in older adults. These results show that NanoFlu with Matrix-M generated enhanced immune responses compared to the unadjuvanted formulation, and importantly, showed superior hemagglutination inhibition antibody (HAI) responses against wild-type A(H3N2) viruses, including drifted strains, when compared to Fluzone High-Dose, the leading flu vaccine in older adults.

Key Upcoming Events

·Continue ongoing discussions with the FDA, European regulatory agencies, and potentially other national regulatory agencies, to assess opportunities for submission of marketing license applications for ResVax.
·Reach agreement with the FDA during the second quarter of 2019 on a proposed Phase 3 study design for NanoFlu utilizing accelerated approval criteria.
·Present ResVax Phase 3 trial data at the 37th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) on May 7, 2019.

Financial Results for the Three and Twelve Months Ended December 31, 2018

Novavax reported a net loss of $49.3 million, or $0.13 per share, for the fourth quarter of 2018, compared to a net loss of $50.8 million, or $0.16 per share, for the fourth quarter of 2017. For the twelve months ended December 31, 2018, the net loss was $184.7 million, or $0.50 per share, compared to a net loss of $183.8 million, or $0.63 per share, for the same period in 2017.

Novavax revenue in the fourth quarter of 2018 was $6.1 million, compared to $10.4 million in the same period in 2017. This 41% decrease was driven by the completion of enrollment of participants in the Prepare trial in the second quarter of 2018.

Research and development expenses decreased 13% to $43.4 million in the fourth quarter of 2018, compared to $49.7 million for the same period in 2017. This decrease was primarily due to decreased development activities of ResVax and lower employee-related costs, partially offset by increased development activities of NanoFlu.

General and administrative expenses increased 8% to $9.2 million in the fourth quarter of 2018, compared to $8.5 million for the same period in 2017. The increase was primarily due to higher professional fees.

Interest income (expense), net for the fourth quarter of 2018 was ($2.8) million, compared to ($3.1) million for the same period of 2017.

As of December 31, 2018, Novavax had $103.9 million in cash, cash equivalents, marketable securities and restricted cash, compared to $186.4 million as of December 31, 2017. Net cash used in operating activities for the fourth quarter of 2018 was $45.3 million, compared to $43.4 million for same period in 2017.

Conference Call

Novavax will host its quarterly conference call today at 4:30 p.m. ET. The dial-in numbers for the conference call are (877) 212-6076 (Domestic) or (707) 287-9331 (International), passcode 9559037. A replay of the conference call will be available starting at 7:30 p.m. ET on March 18, 2019 until 7:30 p.m. ET on March 25, 2019. To access the replay by telephone, dial (855) 859-2056 (Domestic) or (404) 537-3406 (International) and use passcode 9559037.

A webcast of the conference call can also be accessed via a link on the home page of the Novavax website (novavax.com) or through the "Investor Info"/"Events" tab on the Novavax website. A replay of the webcast will be available on the Novavax website until June 18, 2019.

About RSV in Infants

Globally, RSV (respiratory syncytial virus) is the leading viral cause of severe lower respiratory tract disease in infants and young children.1 It is the second leading cause of death in children under one year of age.2 Estimated annual hospitalizations of 1.4 million and an estimated 27,300 in-hospital deaths were due to RSV acute lower respiratory infection in children under six months of age.3 RSV results in a total global economic burden of $6.2 billion annually.

In the U.S., RSV is the leading cause of hospitalization of infants.4 Estimated annual hospitalizations are up to 76,000.5,6 While RSV can impact all infants, babies under six months of age are among those at highest risk, as approximately 77% of all first-year RSV infections occur before six months. In the U.S., the total economic burden is $2.7 billion annually.

About ResVax

ResVax is an RSV fusion (F) protein recombinant nanoparticle vaccine with aluminum phosphate as an adjuvant. It is being developed to protect infants from RSV disease via maternal immunization, which may offer the best method of protection from RSV disease in infants through the first months of life. In February 2019, Novavax announced top-line data from Prepare, a global Phase 3 clinical trial in 4,636 pregnant women, at least 3,000 of whom have received the vaccine, and their infants. Prepare is supported by an $89.1 million grant from the Bill & Melinda Gates Foundation (BMGF).

About Influenza

Influenza is a world-wide infectious disease that causes illness in humans with symptoms ranging from mild to life-threatening or even death. Serious illness occurs not only in susceptible populations such as infants, young children and older adults, but also in the general population largely because of infection by continuously evolving strains of influenza which can evade the existing protective antibodies in humans. An estimated one million deaths globally each year are attributed to influenza.7 Current estimates for seasonal influenza vaccine growth in the top seven markets (U.S., Japan, France, Germany, Italy, Spain and UK), show a potential increase from approximately $3.2 billion in 2012-13 season to $5.3 billion by the 2021-22 season.8

1 Nair, H., et al. (2010) Lancet. 375:1545-1555

2 Losano R., et al. (2012/Dec15) Lancet. 380: 2095

3 Ting S/Nair H. Lancet. 2017/Sep2;390:946

4 Leader S., et al. (2003) J Pediatr. 143: S127

5 Hall CB. N Engl J Med 2009;360:588

6 CDC-Stockman LJ. Pediatr Infect Dis J 2012;31:5

7 Resolution of the World Health Assembly. (2003) WHA56.19.28

8 Influenza Vaccines Forecasts. Datamonitor (2013)

About NanoFluand Matrix M

NanoFlu is a recombinant hemagglutinin (HA) protein nanoparticle influenza vaccine produced by Novavax in its SF9 insect cell baculovirus system. NanoFlu uses HA protein amino acid sequences that are the same as the recommended wild-type circulating virus HA sequences. NanoFlu contains Novavax’ patented saponin-based Matrix-M adjuvant, which is potent and well- stimulates both high quality and durable antibody responses as well as multifunctional CD4 and CD8 T-cell responses. In January 2019, Novavax announced positive top-line data from its Phase 2 clinical trial in older adults of quadrivalent formulations of NanoFlu in 1,375 healthy older adults across clinical sites in the U.S.

About Accelerated Approval

Accelerated approval may be granted for certain biological products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments. Such an approval will be based on adequate and well-controlled clinical trials establishing that the biological product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. For seasonal influenza vaccines, the hemagglutination inhibition (HAI) antibody response may be an acceptable surrogate marker of activity that is reasonably likely to predict clinical benefit. To be considered for accelerated approval, a biologics license application for a new seasonal influenza vaccine should include results from one or more well-controlled studies designed to meet immunogenicity endpoints and a commitment to conduct confirmatory post-marketing studies of clinical effectiveness in preventing influenza.

On March 19, 2019 Bristol-Myers Squibb Company (NYSE: BMY) reported that it has filed a new investor presentation with the Securities and Exchange Commission (SEC) in connection with its previously announced definitive merger agreement with Celgene Corporation (NASDAQ: CELG) (Press release, Bristol-Myers Squibb, MAR 19, 2019, View Source [SID1234534470]).

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The investor presentation is available on the SEC’s website at www.SEC.gov and on Bristol-Myers Squibb’s website at View Source Highlights of the presentation include:

The Celgene acquisition is a financially and strategically compelling transaction.
Enhanced product leadership and pipeline: The combined company will be #1 in oncology, #1 in cardiovascular, and top 5 in immunology and inflammation with nine current products over $1 billion in annual sales, six near-term launches, and robust early-stage pipeline and cutting edge technologies and discovery platforms;
Attractive value: Value of approximately $55 billion from marketed products and in excess of $20 billion from synergies implies that the Celgene pipeline was acquired for a highly attractive price when compared to the aggregate purchase price of $90 billion;
Ideal timing: Trading ratio at two-year lows and Celgene P/E near an all-time low when deal was announced;
Sustainable financial strength: Sales and earnings projected to grow every year through 2025; Significant margin improvement of approximately 800 basis points to 36% on a 2018 pro forma basis before the impact of cost synergies compared to 28% on a standalone basis.
Bristol-Myers Squibb has generated a track-record of financial and operational outperformance.
Strong operating performance drives long-term value creation: Five year CAGRs for net revenue and adjusted EPS of 7% and 17%, respectively, both in excess of peer median, with adjusted operating margin up 725 basis points over that time period. Bristol-Myers Squibb has met or exceeded top line and EPS guidance and estimates on an annual basis each year since 2013;
Industry-leading commercialization: Opdivo is one of the most successful commercial oncology launches and has a leadership position in 16 FDA approved indications and delivered $6.7 billion in 2018 sales, up 36% year-over-year. Additionally, Eliquis is the #1 world-wide novel anti-coagulant despite being the third entrant to market and generated $6.4 billion in 2018 sales, up 32% year-over-year;
Portfolio transition success: Transitioned portfolio through multiple Losses of Exclusivity over the last five years, with approximately 60% of 2018 sales coming from new products launched during that period.
The transaction is the result of a robust process characterized by strong oversight, extensive diligence and focused planning.
Comprehensive process: Prioritized more than 20 transformational and ‘string-of-pearls’ opportunities, and Celgene selected as most attractive opportunity;
Thorough Board oversight: Consistent Board involvement throughout process, with eight meetings to discuss Celgene opportunity;
Extensive diligence: Six-month deep-dive analysis and five subsequent weeks of confidential due diligence provided comprehensive view of Celgene’s opportunities and risks;
Focused and committed to a successful integration: Complementary nature of businesses, strong team in place to manage integration and rigorous planning approach.
The Bristol-Myers Squibb Board unanimously recommends that Bristol-Myers Squibb shareholders vote their shares "FOR" the approval of the issuance of shares of the Company’s common stock in connection with our proposed acquisition of Celgene prior to the Special Meeting, which will be held on April 12, 2019. All Bristol-Myers Squibb shareholders of record as of the close of business on March 1, 2019 will be entitled to vote their shares.

Bristol-Myers Squibb urges shareholders to discard any blue proxy cards and disregard any related solicitation materials sent to you by Starboard Value LP, which is soliciting proxies from Bristol-Myers Squibb shareholders against approving the merger. Irrespective of whether shareholders previously submitted a blue proxy card pertaining to the proposals contained in Bristol-Myers Squibb’s definitive proxy statement, the Company urges shareholders to cast their vote on the WHITE proxy card "FOR" the proposal to approve the transaction.

On March 19, 2019 SOTIO, a biotechnology company owned by the PPF Group, reported results from SOV02, its Phase II clinical trial evaluating DCVAC/OvCa, an active cellular immunotherapy product, in patients with recurrent ovarian cancer at 2019 SGO’s 50th Annual Meeting on Women’s Cancer today (Press release, SOTIO, MAR 19, 2019, View Source [SID1234534471]). Final analysis of SOV02 shows that DCVAC/OvCa decreased the risk of death significantly compared to patients who did not receive DCVAC/OvCa. Clinical trial results were presented during today’s SGO 2019 Plenary Session by SOV02 principal investigator David Cibula, MD, PhD from General University Hospital in Prague (Czech Republic).

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In the randomized, open label SOV02 clinical trial, patients with recurrent ovarian cancer received DCVAC/OvCa in combination with platinum-based chemotherapy. Compared to patients who did not receive DCVAC, it decreased the risk of death by 62%. The combination of chemotherapy and immunotherapy corresponded with 73% survival at two years, compared to 41% survival when chemotherapy was used alone. Overall survival results are statistically significant with a p-value of 0.0032. Progression Free Survival (PFS) increased from 9.5 to 11.3 months. Treatment with DCVAC/OvCa was very well tolerated and did not lead to any treatment discontinuation.

"Results from final data analysis of SOV02 clinical trial show that patients with recurrent ovarian cancer treated with DCVAC/OvCa are living significantly longer than patients in the control group. This outcome stands out very positively in this highly competitive clinical development landscape," said David Cibula, MD, PhD, General University Hospital (Prague, Czech Republic), Past-President of European Society of Gynaecological Oncology (ESGO), principal investigator of SOV02 study.

Radek Spisek, MD, PhD, Chief Executive Officer of SOTIO commented: "We are very happy that the results of SOV02 study in the second line treatment of ovarian cancer confirm the promising data of SOV01 trial in the first line, reported at ASCO (Free ASCO Whitepaper) 2018. In cooperation with ENGOT, we are now setting up the design of the pivotal trial that will build on the results of the Phase II program. With the development of DCVAC/OvCa and the latest result we are addressing the medical need in this harmful disease."

More information and details about the SOV02 clinical trial results can be found in the slides from the oral presentation at SGO 2019 posted on SOTIO’s webpage.

About SOV02 clinical trial:
SOV02 is a randomized, open-label, parallel-group, multi-center Phase II clinical trial evaluating the effect of adding DCVAC/OvCa to standard chemotherapy (carboplatin and gemcitabine) in women with first relapse of platinum-sensitive epithelial ovarian cancer.

On March 19, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) approved Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Hoffmann-La Roche, MAR 19, 2019, View Source [SID1234534499]). This approval is based on results from the Phase III IMpower133 study, which showed that Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS]=12.3 vs. 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54–0.91; p=0.0069) in the intention-to-treat (ITT) population.[1] The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77, 95% CI: 0.62-0.96; p=0.017). Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq.

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"Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.

Results from the Phase III IMpower133 study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.

In the US, Tecentriq is approved in combination with Avastin (bevacizumab), paclitaxel and carboplatin (chemotherapy), for the initial (first-line) treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumour aberrations. In Europe, the Tecentriq and Avastin combination is approved for the initial treatment of people with metastatic non-squamous NSCLC, including people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumour aberrations should have disease progression on FDA approved therapy for NSCLC harbouring these aberrations prior to receiving Tecentriq.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) vs. chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve adults with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were progression-free survival (PFS) as determined by the investigator using RECIST v1.1 and OS in the ITT population.

A summary of the ITT data from the IMpower133 study that support this approval is included below.[1]

Tecentriq in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the ITT population.
The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017).
Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of Tecentriq. Serious adverse reactions occurred in 37% of people receiving Tecentriq plus chemotherapy compared to 35% of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving Tecentriq plus chemotherapy were feeling tired or weak (fatigue/asthenia; 39%), nausea (38%), hair loss (alopecia; 37%), decreased appetite (27%) and constipation (26%) and vomiting (20%).
About SCLC
Lung cancer is the leading cause of cancer death globally.[2] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[2] Lung cancer can be broadly divided into two major types: NSCLC and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.[3]

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. Currently, Roche has nine Phase III lung cancer studies evaluating Tecentriq alone or in combination with other medicines.

In the United States Tecentriq in combination with nab-paclitaxel is approved for treatment of PD-L1-positive metastatic triple-negative breast cancer; and in combination with Avastin and chemotherapy for the initial treatment of people with metastatic non-squamous NSCLC. In the Europe Union, the non-squamous NSCLC indication includes people with EGFR mutant or ALK genomic tumour aberrations after failure of appropriate targeted therapies. Tecentriq is also approved in the European Union, United States and more than 85 countries for people with previously treated metastatic non-small cell lung cancer (NSCLC) and for certain types of untreated or previously treated metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer. By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source

On March 19, 2019 Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the US and Canada, and Pfizer Inc. (NYSE: PFE) reported the discontinuation of the ongoing Phase III JAVELIN Ovarian PARP 100 study evaluating the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib,* a poly (ADP-ribose) polymerase (PARP) inhibitor, versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV) (Press release, Merck KGaA, MAR 19, 2019, View Source [SID1234534472]). The alliance has notified health authorities and trial investigators of the decision to discontinue the trial.

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The decision was based on several emerging factors since the trial’s initiation, including the previously announced interim results from JAVELIN Ovarian PARP 100. The alliance determined that the degree of benefit observed with avelumab in frontline ovarian cancer in that study does not support continuation of the JAVELIN Ovarian PARP 100 trial in an unselected patient population and emphasizes the need to better understand the role of immunotherapy in ovarian cancer. Additional factors include the rapidly changing treatment landscape and the approval of a PARP inhibitor in the frontline maintenance setting. The decision to discontinue the JAVELIN Ovarian PARP 100 trial was not made for safety reasons.

The alliance between Merck KGaA, Darmstadt, Germany, and Pfizer was the first to test an immunotherapy in this indication, given the significant unmet need in the treatment of ovarian cancer. Four out of five women with ovarian cancer are diagnosed with disease that has spread to the lymph nodes or to distant organs.1 Most women with advanced ovarian cancer ultimately die within five years due to refractory, resistant or recurrent disease.2,3

JAVELIN Ovarian PARP 100 (B9991030) is an open-label, international, multi-center, randomized study designed to evaluate the efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III or Stage IV). The primary endpoint is progression-free survival (PFS) as determined based on blinded independent central review (BICR) assessment per RECIST v1.1.

The decision to discontinue the JAVELIN Ovarian PARP 100 trial does not impact the currently approved indications for avelumab or the remainder of the ongoing JAVELIN clinical development program. The program involves at least 30 clinical programs and more than 9,000 patients evaluated across more than 15 different tumor types, including breast, gastric/gastro-esophageal junction, and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.

*Avelumab and talazoparib are under clinical investigation for the treatment of advanced ovarian cancer and have not been demonstrated to be safe and effective for this use.

About Avelumab (BAVENCIO)

Avelumab (BAVENCIO) is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.4-6 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.6-8 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Approved Indications in the US

In the US, the FDA granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Important Safety Information from the BAVENCIO US FDA-Approved Label

BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% (21/1738) of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis was reported in 0.9% (16/1738) of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis, and permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% (8/1738) of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% (98/1738) of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥ 3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% (2/1738) of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% (1/1738) of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO: myocarditis with fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Patients should be premedicated with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent doses based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% (439/1738) of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).

Please see full US Prescribing Information and Medication Guide available at View Source

Indication for talazoparib (TALZENNA) from the US Prescribing Information

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.

Important Safety Information from the TALZENNA US Prescribing Information

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) have been reported in patients who received TALZENNA. Overall, MDS/AML have been reported in 2 out of 584 (0.3%) solid tumor patients treated with TALZENNA in clinical studies.

Myelosuppression consisting of anemia, leukopenia/neutropenia, and/or thrombocytopenia have been reported in patients treated with TALZENNA. Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 39%, 21%, and 15% of patients receiving TALZENNA. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 0.7%, 0.3%, and 0.3% of patients.

Monitor complete blood counts for cytopenia at baseline and monthly thereafter. Do not start TALZENNA until patients have adequately recovered from hematological toxicity caused by previous therapy. If hematological toxicity occurs, dose modifications (dosing interruption with or without dose reduction) are recommended. With respect to MDS/AML, for prolonged hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If the levels have not recovered after 4 weeks, refer the patient to a hematologist for further investigations. If MDS/AML is confirmed, discontinue TALZENNA.

TALZENNA can cause fetal harm when administered to pregnant women. Advise women of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose. A pregnancy test is recommended for females of reproductive potential prior to initiating TALZENNA treatment. Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for at least 4 months after receiving the last dose. Based on animal studies, TALZENNA may impair fertility in males of reproductive potential. Advise women not to breastfeed while taking TALZENNA and for at least 1 month after receiving the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥20%) of any grade for TALZENNA vs chemotherapy were fatigue (62% vs 50%), anemia (53% vs 18%), nausea (49% vs 47%), neutropenia (35% vs 43%), headache (33% vs 22%), thrombocytopenia (27% vs 7%), vomiting (25% vs 23%), alopecia (25% vs 28%), diarrhea (22% vs 26%), and decreased appetite (21% vs 22%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) for TALZENNA vs chemotherapy were anemia (39% vs 5%), neutropenia (21% vs 36%), and thrombocytopenia (15% vs 2%).

The most common lab abnormalities (≥25%) for TALZENNA vs chemotherapy were decreases in hemoglobin (90% vs 77%), leukocytes (84% vs 73%), lymphocytes (76% vs 53%), neutrophils (68% vs 70%), platelets (55% vs 29%), and calcium (28% vs 16%) and increases in glucose (54% vs 51%), aspartate aminotransferase (37% vs 48%), alkaline phosphatase (36% vs 34%), and alanine aminotransferase (33% vs 37%).

Coadministration with P-gp inhibitors or BCRP inhibitors may increase TALZENNA exposure. If coadministering with the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil is unavoidable, reduce the TALZENNA dose to 0.75 mg once daily. When the P-gp inhibitor is discontinued, increase the TALZENNA dose (after 3–5 half-lives of the P-gp inhibitor) to the dose used prior to the initiation of the P-gp inhibitor. When co-administering TALZENNA with other known P-gp inhibitors or BCRP inhibitors, monitor patients for potential increased adverse reactions.

For patients with moderate renal impairment, the recommended dose of TALZENNA is 0.75 mg once daily. No dose adjustment is required for patients with mild renal impairment. TALZENNA has not been studied in patients with severe renal impairment or in patients requiring hemodialysis.

TALZENNA has not been studied in patients with moderate or severe hepatic impairment. No dose adjustment is required for patients with mild hepatic impairment.

Please see full US Prescribing Information available at View Source

Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US

Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find new ways to treat cancer.

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