Gilead 2019: Still Gilead

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One of the world’s great biotechs just keeps churning out innovative new drugs and profits, even after the company’s roller-coaster Sovaldi/Harvoni experience.

 

 

 

 

Gilead Sciences Inc.

333 Lakeside Drive
Foster City, CA 94404
Telephone: 650-574-3000
Website: gilead.com

 

Best-Selling Rx Products

PRODUCT 2018 SALES 2017 SALES

Genvoya

$4,624 $3,674
Truvada  $2,997 $3,134
Epclusa $1,966 $3,510

Odefsey

$1,598 $1,106
Descovy $1,581 $1,218
Harvoni $1,222 $4,370
Atripla $1,206 $1,806
Biktarvy $1,184
Letairis $943 $887
Ranexa $758 $717
Complera/Eviplera $653 $966

Stribild

$644 $1,053

All sales are in millions of dollars.

 

Financial Performance

  2018 2017
Revenue

$22,127

$26,107

Net income

$5,455

$4,628

Diluted EPS

$4.17

$3.51

R&D expense

$5,018

$3,734

  1H 2019 1H 2018
Revenue

$10,966

$10,736

Net income

$3,855

$3,355

Diluted EPS

$3.01

$2.55

R&D expense

$2,217

$2,129

All figures are in millions of dollars, except EPS.

 

Outcomes Creativity Index Score: 8
Manny Awards – 7
Cannes Lions – N/A
LIA: Health & Wellness – N/A
Clio Health – N/A
One Show: HW&P – N/A
MM&M Awards – N/A
Global Awards – 1
Creative Floor Awards – N/A

 

 

In 2014 Gilead’s top-line revenue more than doubled thanks to Sovaldi and Harvoni. In 2015 the two hepatitis C products had more than $19 billion in combined sales. In 2016 they brought in more than $13 billion. Last year, Harvoni sales decreased to $1.22 billion and Sovaldi sales were not listed individually in the company’s 2018 Form 10-K. Quite the ride. But Gilead’s top line has not fallen back to the days before Sovaldi and Harvoni now that the two drugs are past their prime. While the company’s overall sales did decline last year, a group of HIV products, including one that earned blockbuster status in its very first year on the market, has kept Gilead rolling along.

Gilead’s top-line revenue in 2018 was $22.13 billion, down 15.2 percent compared with 2017. That said, net income attributable to the company increased by 17.9 percent to $5.46 billion and earnings per share were up 66 cents to $4.17, though this was a little deceptive due to the $5.5 billion charge the company recorded in 2017 because of U.S. tax reform. In the first half of 2019, top-line revenue rose 2.1 percent to $10.97 billion, net income attributable to Gilead was up more than 14 percent to $3.86 billion, and EPS rose 46 cents to $3.01.

New CEO

In December 2018, Gilead’s Board of Directors named Daniel O’Day chairman of the board and CEO, effective March 1, 2019. O’Day was previously the CEO of Roche Pharmaceuticals, holding that position since 2012, and prior to that he led Roche Diagnostics.

“I have long admired Gilead for its work to develop medicines that have fundamentally changed the way HIV and viral hepatitis are treated,” says new CEO Daniel O’Day. “Together with the Board, leadership team, and Gilead’s 11,000 employees, I look forward to building on this in ways that I believe will – in keeping with Gilead’s mission – transform the lives of millions of individuals.”

The board also appointed Gregg Alton as interim CEO for the period of Jan. 1, 2019 until Mr. O’Day’s start date of March 1. Alton has held a number of executive positions at Gilead over the past 20 years, with experience in legal, medical affairs, policy, and commercial. He previously served as general counsel and in August 2018 was appointed chief patient officer.

“Following a comprehensive search, the board became convinced that Dan is the right leader to bring Gilead into the future,” said John C. Martin, Ph.D., chairman of Gilead’s board of directors, when the new appointment was announced. “He is uniquely qualified to take on this role given his track record of success in highly scientific and competitive therapeutic areas, deep understanding of the evolving healthcare environment around the world, and unwavering commitment to driving innovation across all aspects of a business, which will serve Gilead and our stakeholders well.

“Additionally, Dan brings expertise and values that are aligned with our organization, and I, along with Gilead’s entire board, am confident in his ability to work alongside our talented leadership team and deliver on our ambitious goals.”

After joining Roche Pharmaceuticals in 1987, O’Day held various positions in the United States before moving to Roche headquarters in Switzerland in 1998. During his time in Switzerland, he held leadership roles in Global Marketing and Lifecycle Management. In 2001, he moved to Tokyo to become head of Corporate Planning for Roche Pharmaceuticals in Japan and later moved to Denmark to serve as general manager. He became president of Roche Molecular Diagnostics in California in 2006 and subsequently returned to Roche headquarters to lead the Diagnostics Division before assuming his most recent position. He was a member of the corporate executive committee of F. Hoffmann-La Roche AG and a member of the boards of Shanghai Roche Pharmaceuticals Ltd., Roche (China) Holding, Roche Pharma Schweiz AG, Genentech Inc., Chugai Pharmaceuticals Co., Flatiron Health Inc., and Foundation Medicine Inc. Additionally, he has served as a member of the board of the European Federation of Pharmaceutical Industries and Associations. O’Day holds a Bachelor of Science in Biology from Georgetown University in Washington, D.C. and an MBA from the Columbia Business School at Columbia University in New York.

“I have long admired Gilead for its work to develop medicines that have fundamentally changed the way HIV and viral hepatitis are treated,” Mr. O’Day says. “The company has successfully grown into a global organization, providing access to people around the world, while maintaining its focus on innovative science. Together with the board, leadership team, and Gilead’s 11,000 employees, I look forward to building on this in ways that I believe will – in keeping with Gilead’s mission – transform the lives of millions of individuals.”

Additionally, Dr. Martin stepped down from the company’s board of directors, effective March 1, O’Day’s first day of employment. Also, John F. Milligan, Ph.D., stepped down from his role as president and CEO and as a member of the board at the end of 2018.

Acquisitions and partnerships

In January, Gilead and Yuhan Corp. entered into a licensing and collaboration agreement to jointly develop novel therapeutic candidates for the treatment of patients with advanced fibrosis due to nonalcoholic steatohepatitis. Under the agreement, Gilead will acquire global rights to develop and commercialize novel small molecules against two undisclosed targets in all countries, with the exception of the Republic of Korea where Yuhan will retain certain commercialization rights. Yuhan and Gilead will jointly conduct preclinical research, and Gilead will be responsible for global clinical development. Gilead is responsible for commercialization worldwide, outside of Yuhan’s rights in the Republic of Korea. In connection with this agreement, Yuhan received an upfront payment of $15 million and is eligible to receive up to an additional $770 million in potential milestone payments upon achievement of certain development and commercial milestones, as well as royalties on future net sales. This agreement builds on the companies’ existing commercial collaboration to support the promotion of Gilead’s medicines in the Republic of Korea.

In April, Gilead and Novo Nordisk A/S announced that the companies intend to collaborate on a clinical trial combining compounds from their respective pipelines in nonalcoholic steatohepatitis. The intended clinical trial will be a proof of concept study combining Novo Nordisk’s semaglutide and Gilead’s cilofexor and firsocostat for the treatment of patients with NASH. The companies are also exploring the potential to collaborate on preclinical research to advance understanding of the disease.

Also in April, Gilead and insitro entered into a strategic collaboration to discover and develop therapies for patients with nonalcoholic steatohepatitis. Under the terms of the three-year collaboration, insitro’s proprietary platform will be utilized to create disease models for NASH and discover targets that have an influence on clinical progression and regression of the disease. The insitro Human (ISH) platform applies machine learning, human genetics and functional genomics to generate and optimize unique in vitro models and drive therapeutic discovery and development. The ISH platform will provide insights into disease progression, suggest candidate targets, and predict patient responses to potential therapeutic interventions. Gilead can advance up to five targets identified through this collaboration and will be responsible for chemistry and development against these targets.

Under the terms of the agreement, insitro received an upfront payment of $15 million, with additional near-term payments up to $35 million based on operational milestones. insitro will be eligible to receive up to $200 million for the achievement of preclinical, development, regulatory and commercial milestones for each of the five Gilead targets; and up to low double-digit tiered royalties on net sales. For programs where insitro opts in, it will have the right to jointly develop and detail in the United States, receive a profit share in China, and receive milestone payments and royalties on other ex-U.S. sales.

In May, the Gilead company Kite and Humanigen Inc. announced the formation of a clinical collaboration to conduct a Phase I/II study of lenzilumab, an investigational anti-GM-CSF monoclonal antibody, with Yescarta in patients with relapsed or refractory diffuse large B-cell lymphoma. The objective of this study is to determine the effect of lenzilumab on the safety of Yescarta. Kite is acting as the sponsor of this study and is responsible for its conduct.

GM-CSF has been identified as a potential key signal in the inflammatory cascade triggering toxicities associated with chimeric antigen receptor T cell therapy. Toxicities associated with CAR T therapy include neurologic toxicity and cytokine release syndrome. Pre-clinical evidence suggests that lenzilumab inhibition of GM-CSF may have the potential to disrupt CAR T cell mediated inflammation without disrupting CAR T cell anti-tumor efficacy.

Also in May, Gilead and Goldfinch Bio Inc., a biotechnology company focused on developing precision therapies for patients with kidney diseases, announced a strategic collaboration to discover, develop and commercialize a pipeline of innovative therapeutics for diabetic kidney disease and certain orphan kidney diseases.

Under the multi-year collaboration, Gilead has exclusive options to license worldwide rights to certain products directed toward targets emerging from Goldfinch’s proprietary Kidney Genome Atlas (KGA), a comprehensive registry of patients with kidney diseases integrating genomic, transcriptomic and proteomic data with patient clinical profiles. In addition, Goldfinch will apply its biology platform of human induced pluripotent stem cell-derived kidney cells and kidney organoids to validate targets and support discovery and development of products to which Gilead will have exclusive option rights.

Through sequencing the DNA of a large cohort of diabetic patients with and without kidney disease, Goldfinch will expand the scope of the KGA beyond orphan kidney diseases to include DKD. In addition to target identification and validation, Goldfinch will lead discovery and development activities prior to exercise of exclusive option rights by Gilead, at which time Gilead will be responsible for the development and commercialization of optioned products. Goldfinch retains the option to lead development and co-promote optioned products directed to specific kidney disease targets. The collaboration does not include Goldfinch’s existing programs, GFB-887 and GFB-024, for which Goldfinch retains all rights.

Under the terms of the agreement, Goldfinch received $55 million in upfront payments, including a $5 million equity investment, and an additional $54 million to support the development of the KGA platform for DKD.

Goldfinch is also eligible to receive up to $1.95 billion in potential payments for the first five collaboration programs based on the successful achievement of research, development, regulatory and commercial milestones, and tiered royalties on sales of potential products originating from the collaboration. Additionally, Goldfinch retains the option to equally share in U.S. profits for certain optioned products in certain pre-defined kidney indications. Development costs for profit share products will be shared among the two parties in a manner commensurate with product rights.

In June, Gilead and Carna Biosciences Inc. entered into a research and development collaboration to develop and commercialize small molecule compounds in immuno-oncology and to access Carna’s proprietary lipid kinase drug discovery platform.

Under the terms of the license agreement, Gilead will license from Carna worldwide rights to develop and commercialize inhibitors against an undisclosed immuno-oncology target. Gilead will also have exclusive access to Carna’s proprietary lipid kinase drug discovery platform. In connection with this agreement, Carna received an upfront payment of $20 million and is eligible to receive up to an additional $450 million in potential milestone payments upon achievement of certain development and commercial milestones. Carna will also receive royalties on future net sales.

Also in June, Gilead and Nurix Therapeutics Inc., a company discovering drugs that harness the body’s natural process to control protein levels, announced a strategic collaboration to discover, develop and commercialize a pipeline of targeted protein degradation drugs for patients with cancer and other challenging diseases.

Under the multi-year collaboration, Nurix is using its proprietary drug discovery platform to identify novel agents that utilize E3 ligases to induce degradation of specified drug targets and Gilead will have an option to license drug candidates directed to up to five targets resulting from the work. Nurix will retain the option to co-develop and co-detail up to two programs in the United States. The collaboration excludes Nurix’s lead degradation program, for which Nurix retains all rights.

Under the terms of the agreement, Nurix received an upfront payment of $45 million and will be eligible to receive up to about $2.3 billion in total additional payments based on the successful completion of certain research, pre-clinical, clinical, regulatory and commercialization milestones as well as up to low double-digit tiered royalties on net sales. For those programs that Nurix opts in to co-develop and co-detail, the parties will split development costs as well as profits and losses 50/50 for the United States, and Nurix will be eligible to receive royalties on ex-U.S. sales and reduced milestone payments.

In July, Gilead and Galapagos NV entered into a 10-year global research and development collaboration. Through this agreement, Gilead will gain access to an innovative portfolio of compounds, including six molecules currently in clinical trials, more than 20 preclinical programs and a proven drug discovery platform.

Galapagos received a $3.95 billion upfront payment and a $1.1 billion equity investment from Gilead. The company will use the proceeds to expand and accelerate its research and development programs. Gilead received an exclusive product license and option rights to develop and commercialize all current and future programs in all countries outside Europe. In addition, Gilead and Galapagos have agreed to amend certain terms in the agreement governing filgotinib, the candidate being advanced for rheumatoid arthritis and other inflammatory diseases to provide a broader commercialization role for Galapagos in Europe.

According to company leaders, the collaboration will allow for closer scientific partnership between the companies. Gilead will have access to Galapagos’ established research base, which includes more than 500 scientists, and to Galapagos’ platform, which uses disease-related, human primary cell-based assays to discover and verify novel drug targets. Gilead will also nominate two individuals to Galapagos’ board of directors following the closing of the transaction.

As part of the collaboration, Gilead gained rights to GLPG1690, Galapagos’ Phase III candidate for idiopathic pulmonary fibrosis. Gilead also received option rights for GLPG1972, a Phase IIb candidate for osteoarthritis, in the United States. Both GLPG1690 and GLPG1972 are first-in-class compounds and could offer important mid-stage and late-stage pipeline opportunities for Gilead. In addition, Gilead received option rights on all of Galapagos’ other current and future clinical programs outside of Europe.

Galapagos will fund and lead all discovery and development autonomously until the end of Phase II. After the completion of a qualifying Phase II study, Gilead will have the option to acquire an expanded license to the compound. If the option is exercised, Gilead and Galapagos will co-develop the compound and share costs equally. Gilead will maintain option rights to Galapagos’ programs through the 10-year term of the collaboration and for up to an additional three years thereafter for those programs that have entered clinical development prior to the end of the collaboration term.

If GLPG1690 is approved in the United States, Gilead will pay Galapagos an additional $325 million milestone fee. For GLPG1972, Gilead has the option to pay a $250 million fee to license the compound in the United States after the completion of the ongoing Phase IIb study in osteoarthritis. If certain secondary efficacy endpoints are met, Gilead would pay up to an additional $200 million. Following opt in, Galapagos would be eligible to receive up to $550 million in regulatory and commercial milestones.

For all other programs resulting from the collaboration, Gilead will make a $150 million opt-in payment per program and will owe no subsequent milestones. Galapagos will receive tiered royalties ranging from 20-24 percent on net sales of all Galapagos products licensed by Gilead as part of the agreement.

At the same time, Gilead and Galapagos agreed to amend certain terms around the development and commercialization of filgotinib. Under the amended agreement, Galapagos will have greater involvement in filgotinib’s global strategy and participate more broadly in the commercialization of the product in Europe, providing the opportunity to build a commercial presence on an accelerated timeline.

Gilead and Galapagos will jointly commercialize filgotinib in France, Germany, Italy, Spain and the United Kingdom and retain the 50/50 profit share in these countries that were part of the original filgotinib license agreement. Under the revised agreement, Galapagos will have an expanded commercial role. Galapagos retains exclusive rights in Belgium, the Netherlands, and Luxembourg. The companies will share future global development costs for filgotinib equally, in lieu of the 80/20 cost split provided by the original agreement. Other terms of the original license agreement remain in effect, including the remaining $1.27 billion in total potential milestones and tiered royalties ranging from 20-30 percent payable in territories outside of Belgium, France, Germany, Italy, Luxembourg, the Netherlands, Spain, and the United Kingdom.

Gilead’s equity investment will consist of a subscription for new Galapagos shares at a price of €140.59 per share, representing a 20 percent premium to Galapagos’ 30-day, volume-weighted average price. This will increase Gilead’s stake in Galapagos from about 12.3 percent to 22 percent of the issued and outstanding shares in Galapagos. In addition, Galapagos intends to seek shareholder approval to issue two warrants allowing Gilead to further increase its ownership of Galapagos to up to 29.9 percent of the company’s issued and outstanding shares. The deal includes a 10-year standstill restricting Gilead’s ability to seek to acquire Galapagos or increase its stake in Galapagos beyond 29.9 percent of the company’s issued and outstanding shares, subject to limited exceptions. This deal duly closed in August.

Also in July, Gilead licensed three preclinical antiviral programs from Novartis, including investigational agents with the potential to treat human rhinovirus, influenza and herpes viruses. Under the agreement, Gilead acquired exclusive global rights to develop and commercialize novel small molecules against three undisclosed targets. Novartis received an upfront payment and is eligible to receive up to an additional $291 million in potential milestone payments upon achievement of certain development and commercial milestones, as well as royalties on annual net sales.

Additionally during July, Gilead and the Renown Institute for Health Innovation announced a strategic collaboration to collect and analyze genetic and electronic health data that can enhance the understanding of nonalcoholic steatohepatitis and potentially inform development of treatment options for the disease. Gilead will provide funding to Renown IHI to sequence and analyze the DNA of 15,000 individuals living with NASH or nonalcoholic fatty liver disease as well as a control cohort of 40,000 individuals in Nevada.

Product performance

Genvoya took over as Gilead’s top-selling product in 2018 with sales of $4.62 billion, an improvement of 25.9 percent over the previous year. The product is a combination of four HIV medicines in one pill: elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide. In the first half of 2019, sales of Genvoya declined by 11 percent to $2 billion.

The HIV product Genvoya took over as Gilead’s top-selling product in 2018 with sales of $4.62 billion, up by more than a quarter from the previous year.

Sales of Truvada, also for HIV, declined in 2018 by 4.4 percent to $3 billion. Truvada is a fixed-dose combination of Gilead’s antiretroviral medications TDF and emtricitabine. The product’s sales in the first half of 2019 were $1.32 billion, a drop of 6.6 percent.

The hepatitis C product Epclusa brought in $1.97 billion in sales for Gilead in 2018, a decline of 44 percent. In the first half of 2019, sales of Epclusa along with its authorized generic version totaled $984 million, down 5 percent compared with the first half of 2018.

In January, Epclusa was approved in Japan as a once-daily treatment for adults with chronic hepatitis C virus infection with decompensated cirrhosis, and for patients with chronic HCV infection without cirrhosis or with compensated cirrhosis who have had prior treatment with a direct-acting antiviral therapy. No option had previously been available in Japan for treating chronic HCV infection with decompensated cirrhosis, and there have been limited treatment options for patients with chronic HCV infection who have had prior treatment with a DAA.

The approval of Epclusa in Japan was supported by data from a Phase III clinical study in Japanese patients with HCV infection with decompensated cirrhosis (Study GS-US-342-4019) in which 92 percent of patients who received Epclusa for 12 weeks achieved SVR12 (defined as undetectable HCV RNA 12 weeks after completing therapy). Patients who achieve SVR12 are considered cured of HCV. In a separate Phase III clinical study in Japanese patients with genotype 1 or 2 HCV infection who failed prior DAA therapy (Study GS-US-342-3921), 97 percent of patients who received Epclusa with RBV for 24 weeks achieved SVR12.

Sales of Odefsey rose by nearly half in 2018 to $1.6 billion.

Odefsey, a single tablet regimen of a fixed-dose combination of Gilead’s antiretroviral medications emtricitabine and TAF plus Janssen’s rilpivirine for the treatment of HIV-1 patients, generated $1.6 billion in sales in 2018, a jump of 44.5 percent over the previous year. First-half 2019 sales of Odefsey were $784 million, up 7.8 percent compared with the first half of 2018.

The HIV product Descovy, a fixed-dosed combination of Gilead’s antiretrovirals emtricitabine and TAF, brought in $1.58 billion in sales in 2018, up 29.8 percent versus 2017. In the first six months of 2019, sales of Descovy were an even $700 million, a decline of 8.4 percent versus the first half of 2018.

In March, Gilead announced results from the DISCOVER trial, a two-year Phase III randomized, controlled, double-blind study evaluating the safety and efficacy of the investigational use of once-daily Descovy for HIV pre-exposure prophylaxis, compared with Truvada, in men who have sex with men and transgender women at risk for sexually acquired HIV infection.

In DISCOVER, 5,387 study participants were randomized in a 1:1 ratio and received either Descovy or Truvada. Among the 2,694 participants (4,370 patient-years) who were at risk of HIV-1 infection and received once-daily Descovy, seven HIV infections (HIV incidence 0.16/100 person-years) were reported. Among the 2,693 participants (4,386 patient-years) who were at risk of HIV-1 infection and received Truvada, 15 HIV infections (0.34/100 PY) were reported. Descovy met the pre-established criteria for non-inferiority to Truvada using a stringent rate ratio statistical comparison, as demonstrated by the upper bound of the 95 percent confidence interval for HIV-1 infection rate ratio being less than the predefined non-inferiority margin of 1.62/100 PY.

In July, Gilead presented additional results from the DISCOVER trial evaluating an investigational use of Descovy for HIV pre-exposure prophylaxis (PrEP). In a sub-analysis of the DISCOVER trial, Descovy reached intracellular drug concentration levels above the estimated protective threshold significantly more quickly than Truvada, and additional pharmacokinetic data confirm that these drug concentration levels persist longer than Truvada.

These results were based on a sub-analysis of the DISCOVER trial, a two-year Phase III randomized, controlled, double-blind study evaluating the safety and efficacy of the investigational use of once-daily Descovy for PrEP compared with Truvada for PrEP. The study enrolled adult men and transgender women who have sex with men who were both at substantial and sustained risk for sexually acquired HIV infection.

The primary endpoint of the DISCOVER trial was the incidence of documented HIV infection per 100 person-years, with a minimum follow-up of 48 weeks and at least 50 percent of participants having 96 weeks of follow-up. Descovy met the primary endpoint of non-inferiority. Overall, study participants randomized to Descovy for PrEP had a significantly reduced time to achieve a 90 percent effective concentration (EC90) of tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs), as compared with participants taking Truvada. At Week 4, levels of TFV-DP in PBMCs were 6.3-fold higher with Descovy compared with Truvada, resulting in 98 percent of participants receiving Descovy had drug levels above the EC90 compared with 68 percent of participants taking Truvada. Pharmacokinetic data from separate PK studies demonstrate that after using drugs for 14-28 days, F/TAF users who stop drug still maintain TFV-DP concentrations above the EC90 for at least 60 percent longer than F/TDF users.

In August, FDA’s Antimicrobial Drugs Advisory Committee recommended approval of Descovy for the proposed indication of pre-exposure prophylaxis in men and transgender women who have sex with men by a vote of 16 to 2. The AMDAC reviewed Descovy data from the DISCOVER global Phase III clinical study. The committee also evaluated pharmacokinetic data on Truvada and Descovy for HIV treatment and PrEP in support of the potential use of Descovy for PrEP in cis-gender women, a population that was not part of the DISCOVER study. The committee voted 10 to 8 that there were not adequate data regarding the efficacy of Descovy for PrEP in cis-women.

The hepatitis C product Harvoni – not long ago the world’s No. 2 prescription drug by revenue – generated $1.22 billion in sales in 2018, a decline of 72 percent. Sales of Harvoni and its authorized generic in first-half 2019 were $418 million, down 38.4 percent compared with the first half of 2018.

Atripla, a combination of Gilead’s HIV antiretrovirals TDF and emtricitabine with Bristol-Myers Squibb’s efavirenz, was responsible for $1.21 billion in sales in 2018, a decline of 33.2 percent. In the first six months of 2019, sales of Atripla were $323 million, less than half of the January-June 2018 figure.

Making up for that decrease and then some was Biktarvy, a fixed-dose combination of Gilead’s antiretroviral medications bictegravir, emtricitabine and TAF. Approved by FDA in February 2018 and by the European Commission four months later, the new product went from zero to $1.18 billion in sales for the year. That number is already well in the rear-view this year; in the first half of 2019, Biktarvy generated $1.91 billion in sales.

Approved by FDA in February 2018, Biktarvy brought in $1.18 billion during the medicine’s first 11 months on the market.

In March, Japan’s Ministry of Health, Labour and Welfare approved Biktarvy for the treatment of HIV-1 infection. The approval of Biktarvy was supported by data from four Phase III studies: Studies 1489 and 1490 in treatment-naïve HIV-1 infected adults, and Studies 1844 and 1878 in virologically suppressed adults. The trials comprise a diverse population of 2,415 participants on Biktarvy or an active comparator, including a range of adult age groups and races/ethnicities. Biktarvy met its primary objective of non-inferiority at 48 weeks across all four studies. Through 48 weeks, no participants in any of the four studies developed treatment-emergent virologic resistance while taking Biktarvy, no patients discontinued Biktarvy due to renal adverse events, and there were no cases of proximal renal tubulopathy or Fanconi syndrome. China’s National Medical Products Administration approved Biktarvy for the same indication in August.

Additionally in March, Gilead announced data from two studies evaluating the resistance profile of Biktarvy in virologically suppressed adults switching from dolutegravir/abacavir/lamivudine or a boosted protease inhibitor-based regimen for the treatment of HIV-1. The studies found high rates of virologic suppression with Biktarvy in treatment-experienced adults, regardless of pre-existing resistance to nucleoside reverse transcriptase inhibitors.

Participants in two Phase III Biktarvy switch studies (Studies 1844 and 1878) were followed through two years of therapy in the open-label continuation of these studies past the Week 48 primary endpoints. Documented resistance to study drugs was exclusionary; for the purposes of this retrospective analysis, archived preexisting HIV-1 drug resistance was assessed by historical genotypes and retrospective baseline proviral DNA genotyping. Among adults who switched to Biktarvy from DTG/ABC/3TC or a boosted protease inhibitor (PI)-based regimen, high rates of virologic suppression were observed in the overall population (98 percent) as well as the population with preexisting drug resistance (97 percent), including those with archived M184V/I (95 percent). No patients developed treatment-emergent resistance during the course of the study.

Also in March, Gilead announced 48-week results from a Phase II/III study (Study GS-US-380-1474) evaluating the efficacy and safety of Biktarvy in virologically suppressed adolescents and children at least 6 years of age who are living with HIV. Through Week 48, Biktarvy maintained high rates of virologic suppression with a low incidence of study drug-related adverse events and no treatment-emergent resistance.

The 48-week, single-arm, open-label trial enrolled 50 virologically suppressed adolescents aged 12 to <18 years old and weighing ≥35 kg and 50 virologically suppressed children aged 6 to <12 years old and weighing ≥25 kg. All study participants had an undetectable viral load for at least six months before screening and CD4 cell counts of ≥200 cells/µL. Patients received a full adult strength Biktarvy tablet once daily.

At Week 48, 98 percent of patients maintained an undetectable viral load, as defined by the US FDA snapshot algorithm. The remaining one patient had a reported HIV-1 RNA level of 85 c/ml at Week 48, but re-suppressed and achieved an undetectable viral load within two weeks. No participant in the study developed treatment-emergent resistance.

In July, Gilead presented findings from two Phase III trials – a study demonstrating the effectiveness of switching to Biktarvy in women, and a clinical trial evaluating the potential for the single tablet regimen to be an effective treatment option in virologically suppressed patients with known resistance to nucleo(s)tide or non-nucleo(s)tide reverse transcriptase inhibitors.

MOAB0106 was a international multicenter, randomized, open-label Phase III trial evaluated 470 virologically suppressed women on a baseline regimen of either Genvoya, elvitegravir/cobicistat/F/TDF (150/150/200/300 milligrams) or atazanavir+ritonavir+F/TDF (300+100+200/300 milligrams) who switched 1:1 from these baseline regimens to Biktarvy. The primary endpoint for this study, conducted exclusively in women, demonstrated noninferior maintained virologic suppression, with a low frequency of serious adverse events and no emergent resistance at Week 48. All participants, including those on baseline regimens, switched to Biktarvy through Week 96. At Week 96, 99.5 percent of women who received Biktarvy throughout the study duration and 98.5 percent of women who switched to Biktarvy at Week 48 maintained virologic suppression, with no development of treatment-emergent resistance.

Another Gilead product that has been rapidly ascending the sales charts is the oncologic Yescarta. This new compound was approved by FDA in October 2017 for the treatment of adult patients with relapsed or refractory DLBCL after two or more lines of systemic therapy, and then by the European Commission in August 2018 for the treatment of relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after two or more lines of systemic therapy. In 2018 the medicine generated $264 million in sales. In the first half of 2019 Yescarta brought in $216 million in sales, precisely twice as much as the drug had in the first half of the previous year.

In June, the Gilead company Kite announced findings from two new analyses from the ZUMA-1 trial of Yescarta in adult patients with relapsed or refractory large B-cell lymphoma. These results include a two-year sub-population analysis of efficacy and safety in patients by age, as well as preliminary data from a separate safety management study of patients receiving early steroid intervention for cytokine release syndrome and neurologic events.

Patients with relapsed large B-cell lymphoma in the two-year follow-up were analyzed in two groups – those 65 years or older and those younger than 65 years . With a median follow-up of 27.1 months, the objective response rate per investigator assessment was 92 percent among ≥65 patients and 81 percent in the <65 group, with 75 percent and 53 percent of patients in the respective groups achieving a complete response. At two years, 42 percent of ≥65 patients and 38 percent of <65 patients were in an ongoing response. The 24-month overall survival rate was 54 percent and 49 percent in each respective group.

In a ZUMA-1 safety management study (Cohort 4), patients with relapsed or refractory large B-cell lymphoma treated with Yescarta received earlier steroid intervention beginning when patients experienced Grade 1 neurologic events and at Grade 1 CRS when no improvement was observed after three days of supportive care.

As of the abstract data cut-off, 21 of 40 planned patients had received Yescarta, with a median follow-up of 7.7 months; 76 percent of patients received corticosteroids and 86 percent received tocilizumab. Grade ≥3 adverse events occurred in 95 percent of patients; Grade ≥3 events included decreased neutrophil count (33 percent) and anemia (24 percent). Grade 1 or 2 neurologic events and CRS occurred in 48 percent and 100 percent of patients, respectively. No patients experienced Grade ≥3 CRS, and Grade ≥3 neurologic events occurred in only 10 percent of patients, both numerically lower than in the registrational cohorts of ZUMA-1. ORR per investigator assessment was 81 percent in the cohort, and 62 percent of patients achieved a complete response. The median duration of response has not yet been reached.

In the pipeline

In February, Gilead reported results from STELLAR-4. The Phase III, randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of selonsertib – an investigational, once-daily, oral inhibitor of apoptosis signal-regulating kinase 1 – in patients with compensated cirrhosis (F4) due to nonalcoholic steatohepatitis. The study did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH.

In the trial of 877 enrolled patients who received study drug, 14.4 percent of patients treated with selonsertib 18 milligrams and 12.5 percent of patients treated with selonsertib 6 milligrams achieved a ≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network classification without worsening of NASH after 48 weeks of treatment, compared with 12.8 percent of patients who received placebo.

In March, Gilead and Galapagos announced Week 24 results of FINCH 3, an ongoing, randomized, double-blind, active-controlled Phase III study of the investigational, oral, selective JAK1 inhibitor filgotinib in adults with moderately to severely active rheumatoid arthritis. FINCH 3 evaluated filgotinib in combination with methotrexate and as monotherapy in MTX-naïve patients. The study achieved its primary endpoint in the proportion of patients achieving an American College of Rheumatology 20 percent response (ACR20) at Week 24. The proportion of patients achieving the primary endpoint of ACR20 response at Week 24 was significantly higher for filgotinib 200 mg plus MTX and filgotinib 100 mg plus MTX compared with MTX alone.

The proportion of patients achieving ACR50, ACR70, and clinical remission (DAS28(CRP) < 2.6) at Week 24 was also significantly higher for patients receiving once-daily filgotinib 100 milligrams or 200 milligrams plus MTX compared with patients receiving MTX alone. Additionally, those who received filgotinib experienced greater reduction in the Health Assessment Questionnaire Disability Index compared with those receiving MTX alone at Week 24. Filgotinib 200 milligrams monotherapy inhibited the progression of structural damage at Week 24 compared with MTX alone as assessed by modified total Sharp score.

The co-developers also announced Week 24 results of FINCH 1, an ongoing, randomized, double-blind, placebo- and active-controlled Phase III study of filgotinib in adults with moderately to severely active rheumatoid arthritis. FINCH 1 evaluated filgotinib versus adalimumab or placebo, on a stable background dose of methotrexate in patients with prior inadequate response to methotrexate. The study achieved its primary endpoint for both doses of filgotinib in the proportion of patients achieving an American College of Rheumatology 20 percent response (ACR20) compared to placebo at Week 12.

The proportion of patients achieving ACR50 and ACR70 was significantly greater for filgotinib compared with placebo at Week 12, for both doses. Patients receiving filgotinib 100 milligrams or 200 milligrams had a statistically significant reduction in the Health Assessment Questionnaire Disability Index at Week 12 compared with those receiving placebo. Proportions of patients achieving clinical remission and low disease activity at Week 12 were significantly higher for patients in both filgotinib arms compared with placebo. When comparing low disease activity rates at Week 12, filgotinib 200 milligrams was non-inferior to adalimumab. Filgotinib 100 milligrams and 200 milligrams significantly inhibited the progression of structural damage at Week 24 as assessed by change from baseline in modified total Sharp score compared with placebo.

In April, Gilead announced that STELLAR-3 – a Phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib for patients with bridging fibrosis (F3) due to nonalcoholic steatohepatitis – did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH. In the study of 802 enrolled and dosed patients, 9.3 percent of patients treated with selonsertib 18 milligrams and 12.1 percent of patients treated with selonsertib 6 milligrams achieved a ≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network classification without worsening of NASH after 48 weeks of treatment, versus 13.2 percent with placebo.

In August, Gilead and Galapagos announced that the Marketing Authorization Application for filgotinib for the treatment of adults with rheumatoid arthritis had been validated and is now under evaluation by the European Medicines Agency. The companies plan to file an NDA with FDA before the end of 2019.

The MAA for filgotinib was supported by 24-week data from the Phase III FINCH trials in which once-daily treatment with filgotinib achieved improvements in clinical signs and symptoms, achievement of low disease activity and remission, and inhibition of structural damage for different sub-populations of patients living with RA.