First Year After Launch Special Feature 2019: Straight to the top
The members of the launch class of 2017 wasted no time in passing more established competitors.
Pharma does not seem to have much time for the long, slow rise in sales any more. Today’s brands launch with the hope of winning the pennant in season two, if not season one – and several of the new brands launched in 2017 did or nearly did so, performing as well or better than older peers in their respective markets right away. Mavyret, AbbVie’s newest drug for hep C, led its category in sales during its first full year on the market. Roche/Genentech’s Ocrevus placed third among all multiple sclerosis products in its own first full year. Three other new brands launched in 2017 each generated more than $500 million in 2018 sales. Impatience may not be a virtue, exactly, but in pharma it seems to be paying off.
AbbVie’s Mavyret was approved by FDA in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret was also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both. Mavyret was the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more. FDA’s approval came just a few days after the product was approved by the European Commission, in late July 2017.
“This approval provides a shorter treatment duration for many patients, and also a treatment option for certain patients with genotype 1 infection, the most common HCV genotype in the United States, who were not successfully treated with other direct-acting antiviral treatments in the past,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, upon the drug’s approval.
The safety and efficacy of Mavyret were evaluated during nine clinical trials enrolling about 2,300 adults with genotype 1, 2, 3, 4, 5, or 6 HCV infection without cirrhosis or with mild cirrhosis. Results of the trials demonstrated that 92-100 percent of patients who received Mavyret for eight, 12, or 16 weeks duration had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.
According to AbbVie leaders, up to 95 percent of HCV patients in the United States may be eligible for treatment with Mavyret, including patients with compensated cirrhosis or without cirrhosis and those with limited treatment options, such as patients with chronic kidney disease. About 3.4 million Americans are chronically infected with HCV, and more than 500,000 patients have both chronic HCV and CKD. Mavyret was designed to deliver a cure across all major genotypes and specific treatment challenges, such as patients with severe CKD, and GT1 patients not cured by a NS5A inhibitor or a NS3/4A protease inhibitor (PI) direct-acting antiviral (DAA) treatment, but not both. Mavyret combines two new DAAs that target and inhibit proteins essential for the replication of the hepatitis C virus.
“With Mavyret, physicians and patients now have a treatment option that is highly effective and has the potential to cure the majority of HCV patients in as short as eight weeks, regardless of genotype,” said Michael Severino, M.D., executive VP, research and development and chief scientific officer, AbbVie, after the drug’s approval. “The approval of Mavyret demonstrates AbbVie’s commitment to advancing science to help address unmet needs by delivering a new cure for patients who historically had limited treatment options, including those with genotype 3 HCV, individuals with CKD and certain DAA failure patients.”
In November 2018, AbbVie announced new data for Mavyret in treatment-naïve patients with compensated cirrhosis. Results from the Phase IIIb EXPEDITION-8 study showed that with eight weeks of Mavyret, 100 percent of genotype 1, 2, 4, 5, and 6 patients achieved a sustained virologic response 12 weeks after treatment (SVR12) per protocol analysis.
This analysis was part of the ongoing Phase IIIb EXPEDITION-8 study evaluating the safety and efficacy of Mavyret in treatment-naïve chronic HCV patients with compensated cirrhosis across all major genotypes (GT1-6). The study includes two cohorts; cohort one with genotype 1, 2, 4, 5, 6 chronic HCV-infected patients, and cohort two with genotype 3 (GT3) chronic HCV-infected patients.
“Mavyret is already having a significant impact on people living with HCV,” said Janet Hammond, M.D., Ph.D., VP, infectious diseases development, AbbVie, when the new data were announced. “However, there are still groups of patients who may benefit from a shorter treatment option. We continue to investigate and understand the value of an eight-week treatment regimen for patients, something we recognize as an important step towards HCV elimination.”
During March 2017, FDA approved Genentech’s Ocrevus as the first and only medicine for both relapsing and primary progressive forms of multiple sclerosis. The majority of people with MS have a relapsing form or primary progressive MS at diagnosis.
“The FDA’s approval of Ocrevus is the beginning of a new era for the MS community and represents a significant scientific advance with this first-in-class B cell targeted therapy,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development for Genentech, in the approval announcement. “Until now, no FDA-approved treatment has been available to the primary progressive MS community, and some people with relapsing forms of MS continue to experience disease activity and disability progression despite available therapies. We believe Ocrevus, given every six months, has the potential to change the disease course for people with MS, and we are committed to helping those who can benefit gain access to our medicine.”
In two identical RMS Phase III studies (OPERA I and OPERA II), Ocrevus demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half, slowing the worsening of disability and significantly reducing MRI lesions compared with Rebif (high-dose interferon beta-1a) over the two-year controlled treatment period. A similar proportion of people in the Ocrevus group experienced a low rate of serious adverse events and serious infections compared with people in the high-dose interferon beta-1a group in the RMS studies.
In a separate PPMS Phase III study (ORATORIO), Ocrevus was the first and only treatment to significantly slow disability progression and reduce signs of disease activity in the brain (MRI lesions) compared with placebo with a median follow-up of three years. A similar proportion of people in the Ocrevus group experienced adverse events and a low rate of serious adverse events compared with people in the placebo group in the PPMS study.
In April 2017, Genentech released new data showing that Ocrevus reduced the relapse rate by 55 percent compared with Rebif in a pooled exploratory analysis of the Phase III OPERA I and OPERA II studies in RMS. In a separate Phase II study in relapsing-remitting MS (RRMS) patients, Ocrevus demonstrated rapid and near-complete suppression of brain MRI activity at eight weeks, including new active areas of damage (T1 gadolinium-enhancing lesions) and new or newly enlarging areas of damage (hyperintense T2 lesions), compared with placebo.
Additional analyses of the Phase III OPERA I and II studies demonstrated the efficacy of Ocrevus in people with early RMS (recently diagnosed and without previous treatment). Ocrevus suppressed more than 90 percent of active MRI lesions over two years compared with interferon beta-1a in these patients. In the same early RMS patients, Ocrevus also increased the proportion who achieved No Evidence of Disease Activity (NEDA) by 76 percent compared with interferon beta-1a over two years. NEDA is achieved when a patient has no relapses, no confirmed disability progression, no gadolinium-enhancing MRI lesions and no new or enlarging MRI lesions. These data were consistent with NEDA results observed in the overall Ocrevus-treated population.
In an analysis of pooled data from the Phase III RMS open-label extension (OLE) studies, patients who switched from interferon beta-1a to Ocrevus experienced reductions in relapse rates (unadjusted annualized relapse rate of 0.102 after switching) and MRI brain lesions (0.01 mean number of active lesions [T1 gadolinium-enhancing] and 0.37 new or enlarging T2 lesions after switching). Furthermore, patients who were treated with Ocrevus from the start of the studies showed a sustained benefit after three years.
During June 2017, Genentech announced that new post-hoc analyses from the Phase III clinical trial program in people with relapsing and primary progressive forms of multiple sclerosis (RMS and PPMS) showed that Ocrevus significantly reduced disease activity and disability progression in patients with RMS and PPMS, as measured by No Evidence of Progression or Active Disease (NEPAD), a novel composite endpoint in MS. In RMS, Ocrevus significantly increased the proportion of patients maintaining NEPAD by 82 percent compared with Rebif at 96 weeks in a pooled exploratory analysis of the Phase III OPERA I and II studies. In PPMS patients, Ocrevus more than tripled the proportion of those who maintained NEPAD compared with placebo at 120 weeks in an exploratory analysis of the Phase III ORATORIO study (29.9 percent with OCREVUS versus 9.4 percent with placebo).
In June 2018, Genentech released a new exploratory analysis from the extended control period of the Phase III ORATORIO study in PPMS showing that Ocrevus may significantly delay the time to need a wheelchair by seven years, as measured by the length of time until a person reaches Expanded Disability Status Scale seven or greater (EDSS≥7) using 24-week confirmed disability progression (CDP). People treated with Ocrevus had a 46 percent reduction in the risk of progressing to a wheelchair compared to the placebo-treated group (6.2 percent vs. 9.8 percent risk, respectively). When these results were extended to calculate the median time-to-wheelchair, the data suggest Ocrevus treatment may delay the need for a wheelchair by seven years (19.2 years for Ocrevus vs. 12.1 years for placebo).
Dupixent, developed jointly by Sanofi and Regeneron, was approved by FDA in March 2017 for the treatment of adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. AD, the most common form of eczema, is a chronic inflammatory disease with symptoms often appearing as a rash on the skin. Moderate-to-severe atopic dermatitis is characterized by rashes often covering much of the body, and can include intense, persistent itching and skin dryness, cracking, redness, crusting, and oozing. Dupixent is a human monoclonal antibody that is designed to specifically inhibit overactive signaling of two key proteins, IL-4 and IL-13, which are believed to be major drivers of the persistent underlying inflammation in AD.
Dupixent’s approval was based on data from the global LIBERTY AD clinical program, which included three randomized Phase III pivotal trials known as SOLO 1, SOLO 2 and CHRONOS. The studies examined the use of Dupixent either alone (SOLO 1 or SOLO 2, 1,379 adult patients enrolled) or with topical corticosteroids (CHRONOS, 740 adult patients enrolled) in patients with inadequately controlled moderate-to-severe AD.
In all these studies, Dupixent alone or with topical corticosteroids met the primary and key secondary endpoints. In the SOLO 1 and SOLO 2 studies, treatment with Dupixent as monotherapy significantly improved measures of skin clearing and overall extent and severity of disease. In the CHRONOS study, treatment with Dupixent with topical corticosteroids (TCS) significantly improved measures of overall disease severity at 16 and 52 weeks, when compared to placebo with TCS.
In October 2018, FDA approved Dupixent as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.
“Today’s approval marks a significant development for certain people with moderate-to-severe asthma aged 12 years and older,” said Olivier Brandicourt, M.D., CEO of Sanofi, upon the announcement. “For patients dependent on oral corticosteroids, Dupixent improved lung function, reduced oral corticosteroid use and reduced exacerbations regardless of baseline eosinophil levels. Despite the spectrum of treatments for asthma, there continues to be an unmet need for so many patients with moderate-to-severe asthma, and given that Dupixent works differently than other biologics, there is now a new treatment option for some of these patients. Dupixent has already made a difference for many adults with atopic dermatitis, and we now have the opportunity to do the same for certain adults and adolescents with moderate-to-severe asthma in the U.S.”
In May 2019, the European Commission approved Dupixent for use in adults and adolescents 12 years and older as an add-on maintenance treatment for severe asthma with type 2 inflammation characterized by raised blood eosinophils and/or raised fractional exhaled nitric oxide (FeNO), who are inadequately controlled with high dose inhaled corticosteroid (ICS) plus another medicinal product for maintenance treatment.
The EC approval was based on clinical data from 2,888 adults and adolescents who participated in three pivotal clinical trials from the global LIBERTY ASTHMA program, including the Phase III QUEST and VENTURE studies and a Phase IIb trial.
QUEST enrolled 1,902 patients with persistent asthma and evaluated whether adding Dupixent to standard-of-care therapy could reduce severe exacerbations and improve lung function (measured by FEV1). VENTURE enrolled 210 patients with severe oral corticosteroid-dependent asthma and evaluated whether adding Dupixent to standard-of-care therapy could reduce the use of maintenance oral corticosteroids. The Phase IIb trial enrolled 776 adult patients with moderate-to-severe asthma and evaluated whether adding Dupixent to standard-of-care therapy could improve lung function.
In QUEST, by week 52 exacerbations were reduced by up to 67 percent compared to placebo in patients with eosinophils >=300 cells/microliter and up to 65 percent for those with FeNO levels >=25 parts per billion. In the Phase IIb trial, by week 24 exacerbations were reduced by up to 81 percent compared to placebo in patients with eosinophils >=300 cells/microliter. Also in QUEST, by week 12 Dupixent improved FEV1 by up to 33 percent (versus up to 16 percent for placebo) in patients with blood eosinophils of >=300 cells/microliter and up to 30 percent (versus up to 14 percent for placebo) in patients with FeNO >=25 parts per billion.
In the Phase IIb trial, by week 12 Dupixent improved FEV1 by up to 26 percent (vs. 10 percent for placebo) in patients with blood eosinophils of >=300 cells/microliter. Additionally, in VENTURE, by week 24 more than half of Dupixent patients completely eliminated oral corticosteroids, and overall use reduced by 70 percent (versus 42 percent for placebo).
In June 2019, FDA approved Dupixent for use with other medicines to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled.
“Chronic rhinosinusitis with nasal polyposis can be a debilitating condition,” says John Reed, M.D., Ph.D., Head of Research and Development at Sanofi. “Today’s standard of care – which includes intranasal and systemic corticosteroids and sinus surgery – often leaves patients with CRSwNP with recurring symptoms. In two Phase III trials, Dupixent helped patients significantly reduce their nasal congestion, and many patients experienced significant improvement in their sense of smell in as quickly as four weeks. Treatment with Dupixent also reduced the need for systemic steroids and surgery, and led to improvements in health-related quality of life. Importantly, these patients with co-morbid asthma now have a treatment that can help improve their breathing.”
The FDA approval was based on two pivotal studies (the 24-week SINUS-24 and 52-week SINUS-52) that are part of the Phase III LIBERTY clinical trial program. These studies evaluated Dupixent 300 milligrams every two weeks with standard-of-care mometasone furoate nasal spray (MFNS) compared to placebo injection plus MFNS.
In these trials, Dupixent significantly improved key disease measures and met all primary and secondary endpoints. At 24 weeks, patients treated with Dupixent achieved statistically significant improvements in all primary and secondary endpoints.
FDA granted accelerated approval in May 2017 to AstraZeneca’s Imfinzi for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.
“We are excited to offer Imfinzi as a breakthrough therapy for patients with locally advanced or metastatic bladder cancer,” said AstraZeneca CEO Pascal Soriot upon the approval. “Imfinzi is the cornerstone of our extensive Immuno-Oncology program, in development across many tumor types, as monotherapy and in combination. This first approval for Imfinzi is an important milestone in our return to growth and brings us another step closer to our goal of redefining the way cancer is treated.”
The accelerated FDA approval of Imfinzi, a human monoclonal antibody that blocks PD-L1, was based on data from Study 1108. This Phase I/II trial evaluated the safety and efficacy of Imfinzi in patients with locally advanced or metastatic urothelial carcinoma of the bladder. Patients had progressed while on or after a platinum-containing chemotherapy, including those who progressed within 12 months of receiving therapy in a neoadjuvant or adjuvant setting.
In the study, Imfinzi demonstrated rapid and durable responses, with an objective response rate (ORR) of 17 percent in all evaluable patients, regardless of PD-L1 status, and 26.3 percent in patients with PD-L1 high-expressing tumors. PD-L1 high was defined as .25 percent of tumor cells (TC) or tumor-infiltrating immune cells (IC) expressing membrane PD-L1 if ICs involved >1 percent of the tumor area, or TC.25 percent or IC=100 percent if ICs involved .1 percent of the tumor area. Additionally, about 14.3 percent of all evaluable patients achieved partial response and 2.7 percent achieved complete response.
Of patients who had received only neoadjuvant or adjuvant therapy prior to trial entry, 24 percent responded. Based on a secondary endpoint in this single-arm trial, median time to response was six weeks. Among the total 31 responding patients, 14 patients (45 percent) had ongoing responses of six months or longer and five patients (16 percent) had ongoing responses of 12 months or longer.
In February 2018, FDA approved Imfinzi for the treatment of patients with stage III non-small cell lung cancer (NSCLC) whose tumors are not able to be surgically removed (unresectable) and whose cancer has not progressed after treatment with chemotherapy and radiation (chemoradiation).
“This is the first treatment approved for stage III unresectable non-small cell lung cancer to reduce the risk of the cancer progressing, when the cancer has not worsened after chemoradiation,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “For patients with stage III lung cancer that cannot be removed surgically, the current approach to prevent progression is chemoradiation. Although a small number of patients may be cured with the chemoradiation, the cancer may eventually progress. Patients now have an approved therapy that has been shown to keep the cancer from progressing for a longer time after chemoradiation.”
The approval of Imfinzi for the treatment of Stage III, unresectable NSCLC was based on a randomized trial of 713 patients whose cancer had not progressed after completing chemotherapy and radiation. The clinical trial measured the length of time the tumors did not have significant growth after starting treatment with Imfinzi or a placebo (progression-free survival).
The median progression-free survival for patients taking Imfinzi was 16.8 months compared to 5.6 months for patients receiving a placebo. In addition, the sponsor agreed to a post-marketing commitment to provide additional information from their study to the FDA about how long patients lived following treatment with Imfinzi after chemotherapy and radiation (overall survival).
AstraZeneca announced during May 2018 positive overall survival results for the Phase III PACIFIC trial, a randomized, double-blinded, placebo-controlled, multi-center study of Imfinzi (durvalumab) in patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease had not progressed following platinum-based chemotherapy concurrent with radiation therapy (CRT). A planned interim analysis conducted by an Independent Data Monitoring Committee concluded that the trial had met its second of two primary endpoints by showing statistically significant OS benefit with clinically meaningful improvement in patients receiving Imfinzi compared to placebo.
“The readout of positive overall survival data at the interim analysis of the PACIFIC trial provides additional compelling evidence of the clinical benefit that Imfinzi can offer patients in this earlier stage of lung cancer,” said Sean Bohen, executive VP, global medicines development and chief medical officer, AstraZeneca. “We look forward to sharing these results with Health Authorities to support ongoing regulatory interactions and to update the Imfinzi label with these important data.”
In June 2019, AstraZeneca presented three-year overall survival (OS) results from the PACIFIC trial. The results showed a durable and sustained OS benefit in patients with unresectable, Stage III NSCLC who had not progressed following concurrent chemoradiation therapy (CRT), a previous standard-of-care (SoC) treatment. The OS rate was 57 percent at three years for patients receiving Imfinzi versus 43.5 percent for placebo following concurrent CRT. Median OS was not yet reached with the Imfinzi arm versus 29.1 months for placebo.
Tremfya, developed by Janssen Biotech, was approved by FDA in July 2017 for the treatment of adults living with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The new compound was the first approved biologic therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.
Tremfya (guselkumab) received FDA approval based on results from a clinical development program that included more than 2,000 patients in the Phase III VOYAGE 1, VOYAGE 2, and NAVIGATE studies. In clinical trials, at 16 weeks, at least seven out of 10 Tremfya-treated patients achieved at least 90 percent clearer skin, and more than 80 percent demonstrated cleared or almost cleared skin. Improvements were also demonstrated with Tremfya in psoriasis involving the scalp and in symptoms of plaque psoriasis including itch, pain, stinging, burning and skin tightness at week 16. Treatment with Tremfya resulted in clearer skin that lasted, as nearly nine out of ten treated patients who achieved PASI 90 at week 28 maintained that response at week 48. Versus Humira, at week 24, more than seven out of 10 patients treated with Tremfya reported at least 90 percent clearer skin compared with more than four out of ten patients treated with Tremfya.
“Tremfya represents a significant milestone in the treatment of moderate to severe plaque psoriasis as evidenced by the proven skin clearance demonstrated in the majority of study patients receiving this IL-23–specific therapy at week 16 and up to week 48,” said Andrew Blauvelt, M.D., president of Oregon Medical Research Center and study investigator, when the FDA approval was announced. “We continue to make progress in understanding the science of psoriasis and the important role IL-23 plays in the pathogenesis of this disease, which is another reason why today’s approval of Tremfya is exciting, both as a researcher and a practicing dermatologist.”
In October 2018, Janssen announced new long-term data from the open-label period of the VOYAGE 1 clinical trial demonstrating that stably maintained rates of skin clearance with Tremfya treatment achieved from week 52 (1 year) were maintained through week 156 (3 years) among adult patients with moderate to severe plaque psoriasis. The data showed nearly 83 percent of patients receiving Tremfya in the VOYAGE 1 study maintained at least a 90 percent improvement in the Psoriasis Area Severity Index (PASI 90) response (near complete skin clearance), and an Investigator’s Global Assessment (IGA) score of cleared (0) or minimal disease (1) at week 156.
Results from the open-label extension of the VOYAGE 1 clinical study showed that at week 156, in the combined group of patients initially randomized to Tremfya or to placebo with crossover to Tremfya at week 16, 82.1 percent achieved an IGA score of 0/1 (cleared or minimal disease), 96.4 percent achieved a PASI 75 score, and 82.8 percent achieved a PASI 90 score. At week 156, 53.1 percent of patients achieved an IGA score of 0 and 50.8 percent of patients achieved a PASI 100 response. These measures represent skin completely cleared of psoriasis plaques and are consistent with PASI 100 and IGA 0 results demonstrated at week 100.
In December 2018, Janssen announced results from the ECLIPSE study demonstrating that Tremfya was superior to Cosentyx in treating adults with moderate to severe plaque psoriasis for the primary endpoint assessed at week 48. Data from the multi-center, randomized, double-blind head-to-head Phase III study demonstrated that 84.5 percent of patients treated with Tremfya achieved at least 90 percent improvement in their baseline Psoriasis Area Severity Index (PASI) score at week 48, compared with 70.0 percent of patients treated with Cosentyx.
In February 2019, FDA approved Tremfya One-Press, a single-dose, patient-controlled injector for adults with moderate-to-severe plaque psoriasis. According to Janssen, Tremfya is the first FDA-approved medication of its kind to offer the One-Press patient-controlled injector. “Patients living with plaque psoriasis often struggle with a conventional syringe when administering treatment,” said Newman Yeilding, M.D., head of Immunology Development, Janssen Research & Development LLC. “With the approval of One-Press, patients now have the option to self-administer Tremfya with a novel device that is both simple and intuitive to use.”
In June 2019, Janssen announced top-line results from the Phase III DISCOVER 1 and 2 studies, which evaluated the efficacy and safety of Tremfya compared to placebo in adult patients with active moderate to severe psoriatic arthritis (PsA). Both studies met their primary endpoints of American College of Rheumatology 20 percent improvement (ACR20), and the safety profiles observed for Tremfya in the DISCOVER program were consistent with previous studies of guselkumab and Tremfya current prescribing info.
The DISCOVER program comprises the first-ever Phase III studies evaluating an IL-23 p19 inhibitor for the treatment of psoriatic arthritis. Data from the two DISCOVER studies will serve as the basis of submissions to FDA and the European Medicines Agency seeking approval of Tremfya as a treatment for psoriatic arthritis, which are anticipated for second-half 2019.