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Merck: Key(truda) To The Kingdom

Written by: | josh.slatko@medadnews.com | Dated: Wednesday, October 11th, 2017

 

Easily the fastest grower in Merck’s portfolio, the oncology drug Keytruda is piling up dollars and indications at an impressive rate.

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Merck & Co.

2000 Galloping Hill Road
Kenilworth, NJ 07033
Telephone: 908-740-4000
Website: merck.com

  

Best-Selling Products

Product 2016 Sales 2015 Sales
Januvia, Janumet $6,109 $6,014
Zetia, Vytorin $3,701 $3,777
Gardasil, Gardasil 9 $2,173 $1,908
ProQuad/M-M-R II/
Varivax

$1,640

$1,505

Keytruda    $1,402

$566   

Isentress

$1,387

$1,511

Remicade

$1,268

$1,794

Cubicin    $1,087 $1,127   
Singulair $915 $931
Pneumovax 23    $641 $542   

All sales are in millions of dollars.

 

Financial Performance

  2016 2015
Revenue $39,807 $39,498
Net income $5,712 $4,459
Diluted EPS $2.04 $1.56
R&D expense $7,194 $6,704
  1H2017 1H2016
Revenue $19,365 $19,156
Net income $3,507 $2,339
Diluted EPS $1.27 $0.83
R&D expense $3,545 $3,810

In millions of dollars, except EPS

 

 

Much about 2016 was static for Merck. The company’s top-line revenue barely budged from the year before, and many of its key brands did the same, if they did not go backwards. But at least one brand had a big year for the company in 2016: Keytruda. The company’s prize immuno-oncologic leaped past the $1 billion sales mark for the first time, and rolled on into 2017 with $3 billion in sales a distinct possibility. And the new approvals keep coming; in the four months between February and May, Keytruda added no less than five new indications from FDA.

“The performance of Merck’s broad and balanced portfolio allows us to remain committed to biomedical innovation that saves and improves lives and delivers long-term value to shareholders,” says Kenneth C. Frazier, chairman and CEO of Merck. “The momentum behind our pipeline and key product launches, including the continued growth and expansion of Keytruda into new indications and markets around the world, further reinforces our company’s strategic direction.”

“The momentum behind our pipeline and key product launches, including the continued growth and expansion of Keytruda into new indications and markets around the world, further reinforces our company’s strategic direction,” says Merck CEO Kenneth Frazier.

 

Merck’s total top-line sales in 2016 were $39.81 billion, an improvement of 0.8 percent over the previous year. GAAP net income rose by 28 percent to $5.71 billion and GAAP diluted earnings per share were up 48 cents to $2.04, though this was helped along considerably by a decrease in acquisition and divestiture-related costs and the absence of several other one-time items from the previous year. In the first half of 2017, the top line edged up by 1.1 percent to $19.37 billion, while net income was up an even 50 percent to $3.51 billion and EPS rose 44 cents to $1.27, again assisted by a significant drop in acquisition and divestiture-related costs. Merck executives are projecting full-year 2017 EPS at between $1.60 and $1.72.

 

Keytruda

The oncology drug Keytruda was easily the most impressive performer in Merck’s product portfolio in 2016, with sales leaping from $566 million to $1.4 billion. Keytruda has already more than matched that total during 2017, with first-half sales of $1.47 billion.

All of this impressive growth is being helped along by a glut of approvals and development milestones. In March, FDA approved Keytruda for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy. Under FDA’s accelerated approval regulations, this indication was approved based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In refractory or relapsed cHL, Keytruda is approved for use in adult patients at a fixed dose of 200 milligrams and in pediatric patients at a dose of 2 mg/kg (up to a maximum of 200 milligrams).

The approval was based on data in 210 patients from the KEYNOTE-087 trial, which demonstrated an overall response rate with Keytruda (200 milligrams every three weeks) of 69 percent with a complete remission rate of 22 percent and a partial remission rate of 47 percent. The median follow-up time was 9.4 months. Among the 145 responding patients, the median duration of response was 11.1 months (range 0.0+ to 11.1 months).
In May, FDA approved Keytruda for a first-of-its-kind indication: the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high or mismatch repair deficient, solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication was approved under the FDA’s accelerated approval regulations based on tumor response rate and durability of response.

The accelerated approval was based on efficacy data evaluated in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors enrolled in one of five uncontrolled, open-label, multi-cohort, multi-center, single-arm trials. Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible across the five trials. Across all studies, patients received either Keytruda 200 milligrams every three weeks or 10 mg/kg every two weeks until unacceptable toxicity; or disease progression that was symptomatic, was rapidly progressive, required urgent intervention, or occurred with a decline in performance status; or a maximum of 24 months. For the purpose of assessment of anti-tumor activity across these five trials, the major efficacy outcome measures were overall response rate as assessed by blinded independent central radiologists’ review according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and duration of response. Across all five trials, the efficacy analysis showed an ORR of 39.6 percent with a complete response rate of 7.4 percent and a partial response rate of 32.2 percent. At the time of data cutoff, median duration of response had not yet been reached (range 1.6+ to 22.7+ months), with 78 percent of responding patients having responses of six months or longer.

Also in May, FDA approved Keytruda in combination with pemetrexed (brand name Alimta) and carboplatin (pem/carbo), a commonly used chemotherapy regimen, for the first-line treatment of metastatic nonsquamous NSCLC, irrespective of PD-L1 expression. Under the FDA’s accelerated approval regulations, this indication was approved based on tumor response rate and progression-free survival.

The approval was based on data from KEYNOTE-021, Cohort G1, in 123 previously untreated patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations and irrespective of PD-L1 expression. In this trial, Keytruda + pem/carbo demonstrated an objective response rate that was nearly double the ORR of pem/carbo alone (55 percent compared to 29 percent, respectively; all responses were partial responses). Among patients who received Keytruda + pem/carbo, 93 percent had a duration of response of six months or more (range 1.4+ to 13.0+ months) compared to 81 percent who received pem/carbo alone (range 1.4+ to 15.2+ months). In addition, findings demonstrated an improvement in PFS, with a median PFS of 13.0 months for patients treated with Keytruda + pem/carbo compared to 8.9 months with pem/carbo alone.

Also in May, FDA approved two other new indications for Keytruda: for certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. In the first-line setting, Keytruda is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. This indication was approved under accelerated approval based on tumor response rate and duration of response. In the second-line setting, Keytruda is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The first-line approval was based on data from a multicenter, open-label, single-arm trial, KEYNOTE-052, investigating Keytruda in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. The major efficacy outcome measures were objective response rate, according to the Response Evaluation Criteria In Solid Tumors 1.1, as assessed by independent radiology review, and duration of response. The efficacy analysis showed an ORR of 29 percent, with a complete response rate of 7 percent and a partial response rate of 22 percent.

The second-line approval was based on data from a multicenter, randomized, active-controlled trial, KEYNOTE-045, investigating Keytruda in patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients were randomized to receive either Keytruda 200 milligrams every three weeks or investigator’s choice of any of the following chemotherapy regimens, all given intravenously, every three weeks: paclitaxel 175 mg/m2, docetaxel 75 mg/m2, or vinflunine 320 mg/m2. The major efficacy outcomes were overall survival and progression-free survival, as assessed by a blinded independent central review per RECIST 1.1; additional efficacy outcome measures were ORR, as assessed by BICR per RECIST 1.1, and duration of response.

Keytruda demonstrated superior OS compared to chemotherapy. Findings demonstrated that Keytruda resulted in a 27 percent reduction in the risk of death compared to chemotherapy – with 155 events (57 percent) observed in the Keytruda arm, compared to 179 events (66 percent) in the chemotherapy arm; the median OS was 10.3 months in the Keytruda arm, compared to 7.4 months in the chemotherapy arm. In October 2016, the study was stopped early at the recommendation of an independent Data Monitoring Committee following an interim analysis that showed Keytruda met the superiority thresholds for OS in the overall study population.

Also in May, FDA accepted for review a supplemental biologics license application for Keytruda seeking approval for treatment of patients with recurrent or advanced gastric or gastroesophageal junction adenocarcinoma who have already received two or more lines of chemotherapy. FDA granted Priority Review with a PDUFA date of Sept. 22, 2017. The application was based on data from cohort one of the Phase 2 KEYNOTE-059 trial investigating Keytruda in heavily pretreated patients with recurrent or advanced gastric or gastroesophageal junction adenocarcinoma that has progressed after two or more lines of chemotherapy.

In June, Merck announced results from the Phase II I-SPY 2 TRIAL investigating Keytruda in combination with standard therapy (paclitaxel followed by doxorubicin and cyclophosphamide) as a neoadjuvant (pre-operative) treatment for patients with locally advanced triple-negative breast cancer or hormone receptor-positive/HER2-negative breast cancer. Findings showed that the addition of Keytruda increased the estimated pathologic complete response rate nearly threefold in patients with TNBC (60 percent vs 20 percent) and in patients with HR+/HER2- breast cancer (34 percent vs 13 percent) compared to standard therapy. Overall, based on Bayesian predictive probability of success in a confirmatory Phase III trial, Keytruda has graduated from the I-SPY 2 TRIAL for all signatures in which it was tested.

Additionally in June, Merck announced updated longer-term overall survival data from KEYNOTE-006, the Phase III study evaluating Keytruda in patients with unresectable or metastatic melanoma. The data showed sustained superior survival outcomes for patients receiving Keytruda (monotherapy) compared to ipilimumab in patients who were treatment-naïve or received one prior line of therapy for the treatment of advanced melanoma. The survival benefit was sustained in patients who completed the planned two years of treatment with Keytruda.

In this trial, treatment with Keytruda was associated with a 30 percent improvement in survival; 50 percent of patients in the Keytruda group were alive nearly three years after starting treatment, compared to 39 percent of patients in the ipilimumab group. In addition, Keytruda nearly doubled the rate of progression-free survival at 33.9 months: 31 percent of patients in the Keytruda group were alive and their disease had not progressed, compared to 14 percent of patients in the ipilimumab group.

Also in June, Merck announced updated overall survival findings from KEYNOTE-024, the Phase III study evaluating Keytruda as a monotherapy compared to platinum-containing chemotherapy in the first-line treatment of patients with advanced non-small cell lung cancer whose tumors express high levels of PD-L1 (tumor proportion score of 50 percent or more). The study included patients with squamous and non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations and demonstrated a reduction in the risk of death by 37 percent for Keytruda compared to chemotherapy based on 19 months of median follow-up. Additionally, in an exploratory analysis, progression-free survival 2 (PFS2) – a clinical endpoint used to assess the impact of next-line treatment on disease control – was substantially improved for patients in the Keytruda group compared to the chemotherapy group.

With about eight additional months of follow-up, data showed continued OS benefit with Keytruda over chemotherapy in the first-line treatment of patients with advanced NSCLC whose tumors expressed high levels of PD-L1 – showing an 18-month OS rate of 61.2 percent in the Keytruda group compared to 43 percent in the chemotherapy group; the 12-month OS rate was 70.3 percent in the Keytruda group compared to 54.8 percent in the chemotherapy group. For PFS2, findings based on 19 months of median follow-up showed a 46 percent reduction in the risk of progression after the start of the second-line regimen or death in patients initially randomized to Keytruda compared to patients initially randomized to chemotherapy

In September, Merck announced results of the Phase III KEYNOTE-040 trial investigating Keytruda compared to standard treatment (methotrexate, docetaxel, or cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. The study did not meet its pre-specified primary endpoint of overall survival. The findings include updated survival data showing a 19 percent reduction in the risk of death over standard treatment in the intent-to-treat population, and a median OS of 8.4 months with Keytruda compared to 7.1 months with standard treatment.

Keytruda crossed the blockbuster mark for the first time in 2016 and is tracking to double its sales during 2017.

 

Acquisitions & Collaborations

During May, Merck entered into an exclusive worldwide license agreement with Teijin Pharma for the development, manufacture, and commercialization of an investigational preclinical antibody candidate targeting the protein tau. Changes in tau are associated with a number of diseases affecting the nervous system, including Alzheimer’s disease.

Under terms of the agreement Merck has exclusive world-wide rights to develop, manufacture, and commercialize the anti-tau antibody. In exchange, Merck will make an upfront payment to Teijin Pharma, which is also eligible to receive development, regulatory and sales milestone payments. In addition, Teijin Pharma will receive royalties on product sales and retains an option to co-promote an approved product in Japan.
According to company leaders, the addition of this antibody targeting tau will complement Merck’s portfolio of candidates being investigated for the treatment of Alzheimer’s disease. These include [18F]-MK-6240, a tau ligand being evaluated as a potential Positron Emission Tomography imaging agent for quantifying the brain burden of neurofibrillary tangle pathology in people with AD. Merck is also evaluating verubecestat (MK-8931), an small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1, in a Phase III study of people with prodromal AD.

In July, Merck entered into a global strategic oncology collaboration to co-develop and co-commercialize AstraZeneca’s Lynparza for multiple cancer types. Lynparza is a first-in-class oral poly ADP ribose polymerase inhibitor currently approved for BRCA-mutated ovarian cancer in multiple lines of treatment.

Lynparza’s pipeline has grown significantly in the last few years, with 14 indications currently being developed across several tumor types, including breast, prostate, and pancreatic cancers. The strategic collaboration, company leaders say, is expected to further increase the number of treatment options available to patients.

The companies will develop and commercialize Lynparza jointly, both as monotherapy and in combination trials with other potential medicines. Independently, the companies will develop and commercialize Lynparza in combinations with their respective PD-L1 and PD-1 medicines, Imfinzi and Keytruda. The companies will also jointly develop and commercialize AstraZeneca’s selumetinib, an oral, potent, selective inhibitor of MEK, part of the mitogen-activated protein kinase pathway, currently being developed for multiple indications including thyroid cancer.

Under the terms of the agreement, AstraZeneca and Merck will share the development and commercialization costs for Lynparza and selumetinib monotherapy and non-PD-L1/PD-1 combination therapy opportunities. Gross profits from Lynparza and selumetinib product sales generated through monotherapies or combination therapies will be shared equally. Merck will fund all development and commercialization costs of Keytruda in combination with Lynparza or selumetinib. AstraZeneca will fund all development and commercialization costs of Imfinzi in combination with Lynparza or selumetinib.

As part of the agreement, Merck will pay AstraZeneca up to $8.5 billion in total consideration, including $1.6 billion upfront, $750 million for certain license options, and up to an additional $6.15 billion contingent upon successful achievement of future regulatory and sales milestones.

In September, Merck announced the acquisition of Rigontec, a pioneer in accessing the retinoic acid-inducible gene I pathway, part of the innate immune system, as a novel and distinct approach in cancer immunotherapy to induce both immediate and long-term anti-tumor immunity. Rigontec’s lead candidate, RGT100, is currently in Phase I development evaluating treatment in patients with various tumors. Under the terms of the agreement, Merck, through a subsidiary, will make an upfront cash payment of €115 million to Rigontec’s shareholders; based on the attainment of certain clinical, development, regulatory and commercial milestones, Merck may make additional contingent payments of up to €349 million.

 

In The Pipeline

In February, Merck announced results of the pivotal Phase III clinical study of letermovir, an investigational antiviral medicine for the prevention of clinically significant cytomegalovirus infection in adult (18 years and older) CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant, also known as bone marrow transplant. The study met its primary efficacy endpoint, showing that significantly fewer patients with undetectable CMV DNA at the start of study treatment developed clinically significant CMV infection through Week 24 post-HSCT (using a non-complete equals failure approach, in which patients who discontinued from the study prior to Week 24 post-transplant or had a missing outcome at Week 24 post-transplant were counted as failures). In the study, letermovir prophylaxis was associated with lower all-cause mortality through Week 24 post-HSCT. Based on these results, Merck plans to submit regulatory applications for the approval of letermovir in the United States and EU in 2017.

Also in February, Merck announced the first Phase III study results for V212, the company’s investigational inactivated varicella zoster virus vaccine for the prevention of herpes zoster, also known as shingles, in immunocompromised patients. This was a double-blind, randomized, placebo-controlled, multi-center trial to study safety, tolerability, efficacy and immunogenicity of inactivated VZV Vaccine in Recipients of Autologous Hematopoietic Stem Cell Transplants (auto-HSCT). In the trial, V212 met its primary endpoint and reduced the incidence of confirmed HZ cases by an estimated 64 percent in recipients of auto-HSCT.

Secondary endpoint findings from the study showed that V212 reduced the incidence of moderate-to-severe HZ pain by an estimated 69.5 percent, utilizing the Zoster Brief Pain Inventory (ZBPI) score. V212 demonstrated an estimated 83.7 percent reduction of the incidence of post-herpetic neuralgia beyond 90 days after onset of HZ. In the study PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0 to 10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following auto-HSCT.

Also in February, Merck announced the halting of protocol 017, also known as the EPOCH study, a Phase II/III study evaluating verubecestat in people with mild-to-moderate Alzheimer’s disease. Merck is stopping the study following the recommendation of the external Data Monitoring Committee, which assessed overall benefit/risk during a recent interim safety analysis, and determined that there was “virtually no chance of finding a positive clinical effect.” The eDMC noted that safety signals observed in the study “are not sufficient to warrant stopping study 017,” and recommended that protocol 019, also known as APECS, which is evaluating verubecestat in people with prodromal Alzheimer’s disease, continue unchanged. Results from protocol 019 are expected in February 2019. Results from EPOCH will be analyzed and presented at an upcoming scientific meeting.

In April, Merck announced the first sustained virologic response results 12 weeks after completion of therapy (SVR12, considered virologic cure) from C-SURGE , an ongoing, open label Phase II clinical trial evaluating MK-3682B, the company’s investigational triple-combination therapy in treatment-experienced patients with hepatitis C virus genotype 1 infection for whom treatment with approved direct-acting antiviral regimens had failed. The study showed that 100 percent of patients who completed 16 weeks of treatment plus ribavirin achieved SVR12 and 100 percent of patients who completed 24 weeks of treatment achieved SVR12.

The Phase II C-SURGE study enrolled 94 patients who were randomized to receive a once-daily regimen of MK-3682B for either 16 weeks with ribavirin or 24 weeks without ribavirin; one patient in the 16-week arm withdrew prior to starting treatment. Of the 93 patients who received treatment, 57 had previously received a regimen of ledipasvir/sofosbuvir for 12 to 24 weeks, 14 had previously received ledipasvir/sofosbuvir for 8 weeks and 22 had previously received Zepatier for 12 weeks. Seventy-eight patients who received treatment had at least one baseline NS5A resistance-associated substitution at positions 28, 30, 31, or 93. Eighty patients who received treatment in C-SURGE had GT1a infection, and 40 patients had compensated cirrhosis. In the full analysis set, 98 percent of patients who received MK-3682B for 16 weeks with ribavirin and 100 percent of patients who received MK-3682B for 24 weeks without ribavirin achieved SVR12.

In June, Merck and partner developer Pfizer Inc. announced that two Phase III studies (VERTIS MET and VERTIS SITA) of ertugliflozin, an investigational oral SGLT-2 inhibitor in development to help improve glycemic control in adults with type 2 diabetes, met their primary endpoints. In the studies, both doses of ertugliflozin tested (5 milligrams and 15 milligrams daily) achieved statistically significant reductions in A1C, a measure of average blood glucose over a two- to three-month timeframe, when added to metformin or in initial co-administration with sitagliptin. The partners filed new drug applications for ertugliflozin with FDA and EMA in March; FDA’s PDUFA date is December 2017.

VERTIS MET, a 26-week study, evaluated the efficacy and safety of ertugliflozin in combination with metformin, compared with placebo and metformin, in adults with type 2 diabetes uncontrolled on metformin monotherapy. The study showed patients taking ertugliflozin 5 milligrams or 15 milligrams and metformin experienced greater reductions in A1C compared to placebo (0.7 percent and 0.9 percent, respectively, compared with 0 percent for placebo). Ertugliflozin in combination with metformin also met a secondary endpoint in the study, as significantly more patients taking either ertugliflozin 5 milligrams or 15 milligrams achieved the ADA’s recommended A1C treatment goal of less than 7.0 percent compared with placebo and metformin. As add-on therapy to metformin, treatment with ertugliflozin also resulted in significant reductions in fasting plasma glucose, body weight, systolic blood pressure, and diastolic blood pressure, compared with placebo.

The 26-week VERTIS SITA study compared the efficacy and safety of initial combination therapy with ertugliflozin and Merck’s DPP-4 inhibitor Januvia with placebo. In this study, patients taking ertugliflozin 5 milligrams or 15 milligrams, in combination with Januvia 100 milligrams, experienced greater reductions in A1C compared with patients taking placebo alone (1.6 percent and 1.7 percent, respectively, compared with 0.4 percent in patients taking placebo). Additionally, the co-administration of ertugliflozin and Januvia met a secondary endpoint in the study, as significantly more patients taking ertugliflozin 5 milligrams or 15 milligrams, in combination with Januvia 100 milligrams, achieved the A1C treatment goal of less than 7 percent. Treatment with the initial combination of ertugliflozin and Januvia also resulted in significant reductions in FPG, body weight and SBP, compared with placebo.

In July, Merck announced the presentation of results from the DRIVE-AHEAD study, the second of two pivotal Phase III clinical trials evaluating the efficacy and safety of doravirine, the company’s investigational, non-nucleoside reverse transcriptase inhibitor, for the treatment of HIV-1 infection. At 48 weeks, the study showed that a once-daily single tablet, fixed-dose combination of doravirine (DOR), lamivudine (3TC), and tenofovir disoproxil fumarate (TDF) met its primary efficacy endpoint of non-inferiority based on the proportion of participants achieving levels of HIV-1 RNA less than 50 copies/mL at 48 weeks of treatment, compared to a fixed-dose combination of efavirenz (EFV), emtricitabine (FTC), and TDF, in treatment-naïve adults infected with HIV-1.

In addition, through 48 weeks, statistically significantly fewer patients taking DOR/3TC/TDF reported pre-specified categories of neuropsychiatric events (dizziness, sleep disorders and disturbances, and inability to think clearly or concentrate) than patients receiving the EFV/FTC/TDF regimen. Treatment with DOR/3TC/TDF also showed a statistically significant lower change from baseline in fasting low density lipoprotein cholesterol and non-high density lipoprotein cholesterol compared to EFV/FTC/TDF at Week 48.

Also in July, Merck announced the U.S. launch of Renflexis, a biosimilar of Remicade. Renflexis was approved by FDA on April 21 for all eligible indications and is the first medicine available in the United States under a global biosimilars development and commercialization agreement between Merck and Samsung Bioepis Co. Renflexis will be introduced in the United States at a list price of $753.39, representing a 35 percent discount to the list price of Remicade.

That same month, FDA granted tentative approval for Lusduna Nexvue (insulin glargine injection) 100 units/mL, a follow-on biologic basal insulin in a pre-filled dosing device. Lusduna Nexvue is being developed by Merck with funding from Samsung Bioepis.

With the tentative approval, Lusduna Nexvue has met all required regulatory standards for follow-on biologics of clinical and nonclinical safety, efficacy, and quality, but is subject to an automatic stay due to a lawsuit from Sanofi claiming patent infringement. Under the Hatch-Waxman Act, the initiation of Sanofi’s lawsuit in September 2016 automatically invoked a stay on final FDA approval of Lusduna Nexvue for a period of up to 30 months, or in the event a court finds in favor of Merck, whichever comes sooner.

In August, Merck announced the publication and presentation of results from the REVEAL outcomes study of anacetrapib, the company’s investigational cholesteryl ester transfer protein inhibitor. In the study of 30,449 patients with atherosclerotic vascular disease receiving LDL-C lowering treatment with atorvastatin, anacetrapib significantly reduced the risk of major coronary events (composite of coronary death, myocardial infarction, or coronary revascularization) by 9 percent relative to placebo (10.8 percent vs. 11.8 percent, respectively). The safety of anacetrapib was generally consistent with data from earlier trials of the drug. However, a sub-study also showed that anacetrapib accumulates in adipose tissue with prolonged dosing. Merck is reviewing the results of the trial with external experts and will consider whether to file new drug applications with FDA and other regulatory agencies.

Also in August, FDA granted approval of Lynparza for three indications: new use as a maintenance treatment for recurrent, epithelial ovarian, fallopian tube, or primary peritoneal adult cancer who are in response to platinum-based chemotherapy, regardless of BRCA status; new use of Lynparza tablets (2 tablets twice daily) as opposed to capsules (8 capsules twice daily); and conversion from the current accelerated approval for the use in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer, who have been treated with three or more prior lines of chemotherapy.

In July 2017, Merck entered into an agreement to jointly develop and commercialize AstraZeneca’s Lynparza; during the following month, the oncology drug earned three approvals from FDA.

 

Two randomized trials supported the new approvals and the conversion of accelerated approval to full approval which was originally based on a single-arm trial. The first, SOLO-2, confirmed the benefit of Lynparza in germline BRCA-mutated patients, demonstrating a 70 percent reduced risk of disease progression or death and improved progression-free survival to 19.1 versus 5.5 months for placebo by investigator-assessed analysis. The second, Study 19, showed that Lynparza reduced the risk of disease progression or death by 65 percent and improved PFS compared with placebo in patients of any BRCA status, with a median PFS of 8.4 months versus 4.8 months for placebo. Additionally, patients in Study 19, treated with Lynparza as a maintenance therapy, had a median OS of 29.8 months vs 27.8 months for placebo. Merck is developing Lynparza jointly with AstraZeneca.

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