On September 19, 2020 Novartis reported results of the final overall survival (OS) analysis from the SOLAR-1 trial, which evaluated Piqray (alpelisib) in combination with fulvestrant, compared to fulvestrant alone, in hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer patients with tumors harboring a PIK3CA mutation (Press release, Novartis, SEP 19, 2020, View Source [SID1234565375]). Piqray is the only treatment approved in Europe, the United States and 15 other countries specifically for people with HR+/HER2- advanced breast cancer with a PIK3CA mutation. These data will be presented as a late-breaking oral presentation during the ESMO (Free ESMO Whitepaper) Virtual Congress 2020.

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In the study, there was a clinically relevant improvement in OS of eight months for patients with a PIK3CA mutation taking Piqray plus fulvestrant compared to fulvestrant alone (median OS 39.3 months vs. 31.4 months; one-sided p≤0.0161; HR=0.86; 95% CI: 0.64-1.15; p=0.15)1. This difference did not reach the prespecified threshold of statistical significance set for the secondary objective of OS in patients with PIK3CA-mutated breast cancer. A more than 14 month OS improvement was observed in patients with lung or liver metastases, which signify more aggressive disease (median OS 37.2 months vs. 22.8 months; HR=0.68; 95% CI: 0.46-1.00)1-3.

"These results build on previous data showing that alpelisib nearly doubled median progression-free survival in this patient population," said Fabrice André, MD, PhD, research director and head of INSERM Unit U981, professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France, and global SOLAR-1 principal investigator. "Patients whose tumors have a PIK3CA mutation, particularly those with lung or liver metastases, have a more aggressive, harder to treat cancer, so these results showing alpelisib offers longer life, are promising."
In addition, data showed the need for chemotherapy was delayed in patients taking Piqray plus fulvestrant by nine months compared to those taking fulvestrant alone (23.3 months vs. 14.8 months; HR=0.72; 95% CI: 0.54-0.95)1. Quality of life (QOL) was maintained for people taking Piqray plus fulvestrant.

"These data demonstrating survival benefit give the 40% of HR+/HER2- advanced breast cancer patients with PIK3CA mutations in their tumors more time to spend with loved ones and do what they value most," said Susanne Schaffert, PhD, President, Novartis Oncology. "We are committed to reimagining a world where advanced breast cancer becomes a curable disease, and these data reinforce our confidence as we continue to explore the potential use of Piqray in other types of breast cancer with PIK3CA mutations."

No new safety signals were observed; adverse events were consistent with previously reported SOLAR-1 results.

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In July 2020, the European Commission (EC) approved Piqray in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2- locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy.

About Piqray (alpelisib)
Piqray is a kinase inhibitor developed for use in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after endocrine-based regimen. Piqray is approved in 48 countries, including the US and European member states.

About SOLAR-1
SOLAR-1 is a global, Phase III, randomized, double-blind, placebo-controlled trial studying Piqray in combination with fulvestrant for postmenopausal women, and men, with PIK3CA-mutated HR+/HER2- advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor7-9.

The trial randomized 572 patients. Patients were allocated based on central tumor tissue assessment to either a PIK3CA-mutated cohort (n=341) or a PIK3CA non-mutated cohort (n=231). Within each cohort, patients were randomized in a 1:1 ratio to receive continuous oral treatment with Piqray (300 mg once daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or placebo plus fulvestrant. Stratification was based on visceral metastases and prior CDK4/6 inhibitor treatment7-9. Patients and investigators are blinded to PIK3CA mutation status and treatment.

The primary endpoint is local investigator assessed PFS using RECIST 1.1 for patients with a PIK3CA mutation. The key secondary endpoint is overall survival, and additional secondary endpoints include, but are not limited to, overall response rate, clinical benefit rate, health-related quality of life, efficacy in PIK3CA non-mutated cohort, safety and tolerability7-9.

About Novartis in Advanced Breast Cancer
Novartis tackles breast cancer with superior science, collaboration and a passion for transforming patient care. We’ve taken a bold approach to our research by including patient populations often neglected in clinical trials, identifying new pathways or mutations that may play a role in disease progression and developing therapies that not only maintain, but also improve, quality of life for patients. Our priority over the past 30 years and today is to deliver treatments proven to improve and extend lives for those diagnosed with advanced breast cancer.

Important Safety Information from the PIQRAY EU SmPC
The most common ADRs and the most common grade 3 / 4 ADRs (reported at a frequency >20% and ≥2%, respectively) were plasma glucose increased, creatinine increased, gamma-glutamyltransferase increased, rash, lymphocyte count decreased, nausea, alanine aminotransferase increased, anaemia, fatigue, lipase increased, decreased appetite*, stomatitis, vomiting*, weight decreased, hypocalcaemia, plasma glucose decreased*, activated partial thromboplastin time prolonged*, alopecia**, diarrhoea, hypokalaemia, hypertension, nausea, creatinine increased, and mucosal inflammation (*<2% grade 3/4 ADRs reported, ** no grade 3/4 ADRs reported).

Piqray can cause serious side effects such as severe hypersensitivity, severe cutaneous reactions, hyperglycaemia, pneumonitis, diarrhoea and osteonecrosis of the jaw.

The following should be taken into consideration prior to or during treatment with Piqray:

Piqray should be permanently discontinued in patients with serious hypersensitivity reactions.

Piqray should not be initiated in patients with a history of severe cutaneous reactions, should be interrupted if signs or symptoms of severe cutaneous reactions are present, and permanently discontinued if a severe cutaneous reaction is confirmed.

Fasting glucose and HbA1c levels should be monitored frequently in the first 4 weeks of treatment, and patients should be advised of the signs and symptoms of hyperglycaemia.

In case of new or worsening respiratory symptoms, the patient should be evaluated for pneumonitis.

Patients should be advised to notify their physician if diarrhoea occurs.

Caution should be exercised when Piqray and bisphosphonates or denosumab are used together or sequentially. Piqray should not be initiated in patients with ongoing osteonecrosis of the jaw.

The efficacy and safety of Piqray has not been studied in patients with symptomatic visceral disease.

Animal studies suggest that Piqray may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Piqray during treatment and at least 1 week after stopping treatment. Women should not breast feed for at least 1 week after the last dose of Piqray. Piqray may affect fertility in males and females.

On September 19, 2020 Novartis reported detailed results from the Phase III COMBI-i trial evaluating the investigational immunotherapy spartalizumab (PDR001) in combination with the targeted therapies Tafinlar (dabrafenib) and Mekinist (trametinib) compared to Tafinlar + Mekinist alone1 (Press release, Novartis, SEP 19, 2020, View Source [SID1234565374]). The efficacy data achieved in the trial’s control arm among patients treated with Tafinlar + Mekinist represent the longest progression-free survival results (PFS) observed across multiple Phase III studies. The trial did not meet its primary endpoint of investigator-assessed progression-free survival (PFS) for patients treated with the investigational triplet therapy1-4.

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The COMBI-i study was conducted among treatment-naive patients with advanced BRAF V600 mutation-positive cutaneous melanoma. Results were presented today as a late-breaking oral presentation during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 20201.

"For treating physicians and patients alike, the durable, progression-free survival seen with dabrafenib + trametinib in COMBI-i confirms that this targeted therapy combination remains a gold standard treatment for people with advanced BRAF-mutated melanoma," said Dr. Paul Nathan, consultant medical oncologist, Mount Vernon Cancer Centre, United Kingdom, and COMBI-i principal investigator. "The good news is that the control arm of the study performed better than we originally expected, with the efficacy of dabrafenib + trametinib improving consistently over time. Although the study did not meet its primary endpoint, an important trend was seen in favor of the triple therapy arm. There is clearly more for us to learn about patients who may benefit from the potential addition of an immunotherapy."

Findings from this randomized, double-blind, placebo-controlled study showed a median time of PFS of 16.2 months for patients treated with the triple therapy (n=267) compared to 12.0 months for patients receiving the combination Tafinlar + Mekinist alone (n=265; hazard ratio [HR] 0.82; 95% CI 0.655-1.027; p=0.042)1. Overall response rate was 68.5% for spartalizumab with Tafinlar + Mekinist (95% CI, 62.6-74.1%) compared to 64.2% for Tafinlar + Mekinist alone (95% CI, 58.1-69.9%)1. A significant duration of response (DOR) was seen in the study as median DOR for the triple therapy was not reached at two-year data cutoff, compared to 20.7 months with Tafinlar + Mekinist1.

"Working with our clinical investigator partners and melanoma patients around the world, we undertook the COMBI-i study to learn more about how we can continue to improve patient outcomes, and we are proud that it advanced the community’s scientific understanding about potential triplet therapies," said Jeff Legos, Ph.D., MBA, Senior Vice President and Head of Oncology Drug Development. "The study results reinforce that patients taking Tafinlar + Mekinist continue to see durable responses and a meaningful progression-free survival benefit, consistent with data reported in previous Phase III studies."

"As we continue to deliver Tafinlar + Mekinist to patients around the world, Novartis will continue to advance the science with bold investigations into uses for immunotherapy in cancer, including the ongoing development of spartalizumab, across a range of tumor types," Legos added.

About the COMBI-i Study1
COMBI-i was a Phase III, double-blinded global study (NCT02967692) evaluating the investigational anti-PD1 therapy spartalizumab in combination with Tafinlar + Mekinist compared to Tafinlar + Mekinist and placebo as first-line therapy in patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma. The study was conducted in three parts. In the safety run-in (part 1), the primary endpoint was incidence of dose-limiting toxicities, and in the biomarker cohort (part 2), the primary endpoint was immune microenvironment and biomarker modulation. In the randomized portion of the study (part 3), the primary endpoint was investigator-assessed progression-free survival.

COMBI-i study participants were classified as having either Stage IIIC (unresectable) or Stage IV (metastatic) disease and received study treatments as first-line therapy. No new side effects were seen and the safety profile in the control arm was consistent with what has been observed in previous studies. COMBI-i also evaluated a new side effect management protocol to address pyrexia – or fever – a common side effect seen among targeted therapies.

Serious treatment-related adverse events (TRAEs) grade ≥3 occurred in 23.2% of patients in the triple therapy arm compared to 11% in the Tafinlar + Mekinist arm. The most common grade ≥3 adverse events independent of treatment relationship observed in the triple therapy and Tafinlar + Mekinist arms were blood creatine phosphokinase increase (7.9% vs 7.2%), pyrexia (5.2% vs 3.0%), aspartate aminotransferase increase (3.7% vs 1.1%), fatigue (3.4% vs 1.9%), rash (3.4% vs 0.4%), asthenia (2.2% vs. 1.1%), headache (1.1% vs. 1.5%), diarrhea (0.7% vs. 1.9%), nausea (0.7% vs 0.4), arthralgia (0.7% vs 1.5%), and chills (zero vs. 0.8%). TRAEs leading to discontinuation of all 3 study drugs occurred in 12% compared to 8% of patients, respectively.

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About Spartalizumab (PDR001)
Spartalizumab is an investigational monoclonal antibody directed against the human programmed death-1 (PD-1) receptor. Its development program continues, investigating the immunotherapy across a range of tumor types.

About Tafinlar + Mekinist2-4
The combination of the targeted therapies Tafinlar + Mekinist, the worldwide leader in BRAF/MEK-inhibition, is approved for the treatment of patients with unresectable or metastatic BRAF-mutated melanoma by the US Food and Drug Administration (FDA) and European Commission based on data from the pivotal Phase III COMBI-d and COMBI-v trials.

In COMBI-d, Tafinlar + Mekinist achieved a statistically significant overall survival (OS) benefit compared to Tafinlar monotherapy (median of 25.1 months vs 18.7 months; Hazard Ratio [HR] 0.71 [95% Confidence Interval (CI), 0.55-0.92], p=0.01). The median progression-free survival (PFS) was 9.3 months in the 211 patients receiving combination therapy compared to 8.8 months in the 212 patients receiving monotherapy (HR 0.75 [95% CI, 0.57-0.99], p=0.035).

In COMBI-v, Tafinlar + Mekinist demonstrated a statistically significant OS benefit compared to vemurafenib monotherapy (median not reached vs 17.2 months; HR 0.69 [95% CI, 0.53-0.89], p=0.005). The median PFS was 11.4 months in the 352 patients receiving the Tafinlar + Mekinist combination compared to 7.3 months in the 352 patients receiving vemurafenib monotherapy (HR 0.56 [95% CI, 0.46-0.69], p<0.001).

Tafinlar + Mekinist Indication and Important Safety Information
Tafinlar and Mekinist are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
That has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene
Tafinlar and Mekinist are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

That has spread to other parts of the body and you have no satisfactory treatment options, and
That has a certain type of abnormal "BRAF" gene
Tafinlar, in combination with Mekinist, should not be used to treat people with wild-type BRAF melanoma. Mekinist should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that Tafinlar and Mekinist, in combination, are right for you.

It is not known if Tafinlar and Mekinist are safe and effective in children.

Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.
Tafinlar may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with Tafinlar and Mekinist and for at least 4 months after the last dose of Tafinlar and Mekinist. For women of reproductive potential, Tafinlar and Mekinist, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with Tafinlar and Mekinist in combination, and for 4 months after stopping treatment with Tafinlar and Mekinist. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

On September 19, 2020 Novartis reported FDA approval for its breast cancer drug Piqray in HR-positive/HER2-negative patients with PIK3CA mutations last year, early survival data was impressive: Combining the drug with AstraZeneca’s Faslodex nearly doubled the time to disease progression or death to 11 months over Faslodex alone (Press release, Novartis, SEP 19, 2020, View Source [SID1234565372]).

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Now the final survival data from that trial, called Solar-1, is out. And while the overall survival rate wasn’t quite as dramatic, Novartis sees reason to celebrate—particularly for one subset of very sick patients.

The Piqray-Faslodex combo boosted overall survival for patients in the trial by eight months over Faslodex alone—too small a difference to reach statistical significance, Novartis announced during the virtual meeting of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper).

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But among patients with lung or liver metastases, overall survival improved by more than 14 months, to a median of 37.2 months.

"That was really impressive and very clinically meaningful," Jeff Legos, senior vice president and global program head of Novartis Oncology, said in an interview. "Patients with advanced breast cancer who have had their disease metastasize to the lung or liver generally do much worse on available therapy. I think this further reiterates the benefit [Piqray] can provide."

The data showed that overall, patients taking Piqray plus Faslodex had a 14% lower risk of disease progression or death—a number that might not look that impressive on the surface, Legos acknowledged.

"But what’s also important for patients is their median overall survival," he said. "Here we show that patients are living on average eight months longer, which gives them that much more time to spend with family and friends and celebrate milestones."

RELATED: Novartis grabs blockbuster cancer nod for Piqray on double good news day

Novartis hopes the new data will help elucidate some key points of the marketing pitch for Piqray. One of those is quality of life. Patients in the trial taking the Piqray-Faslodex combination were able to delay chemotherapy by a median time of 23.3 months, versus 14.8 months for the patients taking Faslodex alone. Although the combination did produce some side effects—hyperglycemia was the most common complaint—toxicity overall was lower than it typically is for patients on chemotherapy, Legos said. "So they had eight-and-a-half months of a higher quality of life," he said.

Novartis was also able to parse the data from the trial using a biomarker called circulating tumor DNA. When a patient’s tumors are shedding so much of their genetic material that the cancer can be detected in blood, that’s a sign of aggressive disease and a poor prognosis, Legos said.

In patients who had detectable circulating tumor DNA at the start of the trial, Piqray plus Faslodex reduced the risk of death by 26%. "It’s just more evidence that there are patients who definitely are underserved with existing therapy and that [Piqray] does demonstrate a survival advantage," Legos said.

RELATED: Novartis, after 5 blockbuster nods in 2019, hopes for 25 more in the coming years

Novartis has often cited Piqray as a likely blockbuster. There are other PIK3 inhibitors on the market, including Verastem Oncology’s Copiktra and Gilead’s Zydelig, but Piqray was the first to gain a breast cancer nod.

Novartis has an ambitious development plan for the drug going forward. It’s preparing to file for approval in patients with a rare disorder called PIK3CA overgrowth syndrome. Novartis is also hoping to move the drug into triple-negative and HER2-positive breast cancer, as well as ovarian and head and neck cancer.

Piqray brought in sales of $79 million in the second quarter of this year, up from $74 million in the previous quarter. The European Commission approved Piqray in July, and analysts are expecting total sales to surpass $700 million in 2024, according to EvaluatePharma. Moody’s predicts sales will peak at $1 billion a year.

Piqray’s first FDA nod came courtesy of the agency’s Real-Time Oncology Review program—a boon for Novartis, Legos said. "The overall submission and review cycle was incredibly fast," he said. "As soon as data became available we were able to share it with the FDA and engage with them. It was a collaborative relationship, with the patient in mind."

On September 18, 2020, Vertex Pharmaceuticals Incorporated, a Massachusetts corporation (the "Company" or "we") reported that entered into a Credit Agreement (the "Credit Agreement"), with Vertex Pharmaceuticals (Europe) Limited, a private limited company incorporated in England and Wales and a wholly-owned subsidiary of the Company, as a co-borrower, Vertex Pharmaceuticals (Ireland) Limited, a private company limited by shares incorporated in Ireland and a wholly-owned subsidiary of the Company, as a co-borrower, certain other wholly-owned subsidiaries of the Company as subsidiary guarantors, Bank of America, N.A and the other lenders referred to therein, which is summarized below (Filing, 8-K, Vertex Pharmaceuticals, SEP 18, 2020, View Source [SID1234565429]). The Credit Agreement provides for a $2.0 billion senior unsecured revolving facility. The Credit Agreement also provides that, subject to satisfaction of certain conditions, we may request that the borrowing capacity under the Credit Agreement be increased by an additional $500 million. The Credit Agreement matures on September 18, 2022.

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Proceeds of borrowings under the Credit Agreement will be used for general corporate purposes. Loans will bear interest, at our option, at either a base rate or a Eurocurrency rate, in each case plus an applicable margin. Under the Credit Agreement, the applicable margin on base rate loans ranges from 0.500% to 0.875% and the applicable margin on Eurocurrency loans ranges from 1.500% to 1.875%, in each case, based on our consolidated leverage ratio (the ratio of our total consolidated funded indebtedness to our consolidated EBITDA for the most recently completed four fiscal quarter period). Loans under the Credit Agreement may be prepaid at par and commitments under the Credit Agreement may be reduced at any time, in whole or in part, without premium or penalty (except for LIBOR breakage costs).

Loans will be guaranteed by certain of our existing and future domestic subsidiaries, subject to certain exceptions.

The Credit Agreement contains customary representations and warranties and affirmative and negative covenants, including financial covenants to maintain (x) subject to certain limited exceptions, a consolidated leverage ratio of 3.50 to 1.00, subject to an increase to 4.00 to 1.00 following a material acquisition and (y) a consolidated interest coverage ratio of 2.50 to 1.00, in each case to be measured on a quarterly basis. The Credit Agreement also contains customary events of default. In the case of a continuing event of default, the administrative agent would be entitled to exercise various remedies, including the acceleration of amounts due under any outstanding loan.

On September 18, 2020 Baudax Bio, Inc. (NASDAQ:BXRX), a pharmaceutical company focused on therapeutics for acute care settings, reported Gerri Henwood, the Company’s President and Chief Executive Officer, will present at the Oppenheimer Fall Healthcare Life Sciences & Medtech Summit on Tuesday, September 22, 2020 at 3:20 p.m. ET (Press release, Baudax Bio, SEP 18, 2020, View Source [SID1234572274]).

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A live webcast of the presentation will be available on the "Presentations" page within the Investors section of the Baudax Bio website at View Source A replay will be available on the Baudax Bio website for a period of 30 days following the event.