FDA Grants Priority Review to Genentech's Emicizumab for Hemophilia A with Inhibitors

Application based on positive results of Phase III study in adults and adolescents with hemophilia A with inhibitors and interim Phase III results in children

 

Wednesday, August 23, 2017

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for emicizumab prophylaxis (preventative) as a once-weekly subcutaneous treatment for adults, adolescents and children with hemophilia A with factor VIII inhibitors. Nearly one in three people with hemophilia A develop inhibitors to standard factor VIII replacement therapies, which limits treatment options and increases the risk of life-threatening bleeds and repeated bleeds, particularly in joints, that cause long-term damage.

“Genentech has a history of developing innovative antibody therapies to address some of the highest unmet medical needs,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Results of our Phase III study in adults and adolescents as well as early Phase III results in children showed that emicizumab has significant potential to help people with hemophilia A with inhibitors, who face major challenges in preventing and treating bleeds. We are working with the FDA to hopefully bring this new prophylactic treatment option to the hemophilia A inhibitor community as soon as possible.”

The BLA for emicizumab is based on results from the Phase III HAVEN 1 study in adults and adolescents 12 years of age and older, as well as interim results from the Phase III HAVEN 2 study in children younger than 12 years of age. Results from HAVEN 1 were published in The New England Journal of Medicine (NEJM) and results from both studies were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress in July 2017.

The FDA is expected to make a decision on approval by February 23, 2018. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. The FDA granted Breakthrough Therapy Designation for emicizumab in adults and adolescents with hemophilia A with inhibitors in September 2015. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat a serious condition with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies.

Data from both HAVEN 1 and HAVEN 2 have also been submitted for approval consideration to the European Medicines Agency (EMA) and will be reviewed under accelerated assessment. Additional studies evaluating emicizumab in people with hemophilia A both with and without inhibitors and exploring less frequent dosing regimens are ongoing.

About HAVEN 1 (NCT02622321)

HAVEN 1 is a randomized, multicenter, open-label, Phase III study evaluating the efficacy, safety and pharmacokinetics of emicizumab prophylaxis compared to on-demand bypassing agents (BPAs) (no prophylaxis; episodic use only) in adults and adolescents with hemophilia A with inhibitors to factor VIII. The study included 109 patients (12 years of age and older) with hemophilia A with inhibitors to factor VIII, who were previously treated with BPAs on-demand or as prophylaxis. Patients previously treated with on-demand BPAs were randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B). Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (Arm C). Additional patients previously on BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (Arm D). On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.

The primary endpoint of the study is the number of treated bleeds over time with emicizumab prophylaxis (Arm A) compared with no prophylaxis (Arm B). Secondary endpoints include all bleed rate, joint bleed rate, spontaneous bleed rate, target joint bleed rate, health-related quality of life (HRQoL)/health status, and intra-patient comparison to bleed rate on their prior prophylaxis regimen with BPAs (Arm C) or no prophylaxis (Arm B). The study also evaluated safety and pharmacokinetics.

In the HAVEN 1 study, the primary endpoint showed a clinically meaningful and statistically significant reduction in treated bleeds of 87 percent (risk rate [RR]=0.13, p<0.0001) with emicizumab prophylaxis compared with on-demand (no prophylaxis; episodic use only) BPAs. All 12 secondary endpoints were positive, including a statistically significant reduction of 79 percent (RR=0.21, p=0.0003) in treated bleeds in a first-of-its-kind intra-patient analysis comparing two prophylaxis regimens (emicizumab and BPAs) in a subset of patients. Adverse events (AEs) occurring in five percent or more of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection and joint pain (arthralgia).

As previously reported, two patients experienced thromboembolic events (TE) and three patients had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of the BPA activated prothrombin complex concentrate on average for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa. Neither TE event required anti-coagulation therapy and one patient restarted emicizumab. The cases of TMA observed were transient, and one patient restarted emicizumab.

About HAVEN 2 (NCT02795767)

HAVEN 2 is a single-arm, multicenter, open-label, Phase III study evaluating the efficacy, safety and pharmacokinetics of once-weekly subcutaneous administration of emicizumab. The interim analysis after a median of 12 weeks of treatment included 19 children (younger than 12 years of age) with hemophilia A with inhibitors to factor VIII, who require treatment with BPAs. The objectives of the study are to evaluate the number of treated bleeds over time with emicizumab prophylaxis, safety, pharmacokinetics, HRQoL and proxy HRQoL with aspects of caregiver burden.

Interim results from the single-arm HAVEN 2 study were consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds. The study also indicated that emicizumab, with a once-weekly subcutaneous dosing, may help alleviate some of the burden of hemophilia treatment for children and their parents. The most common AEs were mild injection site reactions and common cold symptoms (nasopharyngitis). No TE or TMA events were observed.

About emicizumab (ACE910)

Emicizumab is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process. Emicizumab is administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly. Emicizumab is being evaluated in pivotal Phase III studies in people 12 years of age and older, both with and without inhibitors to factor VIII, and in children younger than 12 years of age with factor VIII inhibitors. Additional trials are exploring less frequent dosing schedules. The clinical development program is assessing the safety and efficacy of emicizumab and its potential to help overcome current clinical challenges: the short-lasting effects of existing treatments, the development of factor VIII inhibitors and the need for frequent venous access. Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech.

About hemophilia A 

Hemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60 percent of people living with a severe form of the disorder. People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles. These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage. In addition to impacting a person’s quality of life, these bleeds can be life-threatening if they go into vital organs, such as the brain. A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible to obtain a level of factor VIII sufficient to control bleeding. People with hemophilia A who develop inhibitors will typically infuse BPA therapies, either on-demand (episodic) or as prophylaxis, to control bleeding. This approach is known to be less effective and less predictable than factor VIII replacement therapy in people with hemophilia A without inhibitors.

About Genentech in hemophilia 

In 1984, Genentech scientists were the first to clone recombinant factor VIII in response to the contaminated hemophilia blood supply crisis of the early 1980s. For more than 20 years, Genentech has been developing medicines to bring innovative treatment options to people with diseases of the blood within oncology, and is investigating emicizumab as a potential treatment option for hemophilia A. Genentech is committed to improving treatment and care in the hemophilia community by delivering meaningful science and clinical expertise. For more information visit http://www.gene.com/hemophilia.

 

Genentech Alliance and Advocacy Relations, Hemophilia

Genentech, a member of the Roche Group, announced positive interim results from the phase III HAVEN 2 study evaluating

emicizumab prophylaxis in children less than 12 years of age with hemophilia A and inhibitors to factor VIII.

-Emicizumab prophylaxis reduced the number of bleeds in children with hemophilia A and inhibitors to factor VIII. These results build upon data reported from the phase III HAVEN 1 study.

The press release is attached below:

Genentech, a member of the Roche Group, this evening announced positive interim results from the phase III HAVEN 2 study evaluating emicizumab prophylaxis in children less than 12 years of age with hemophilia A and inhibitors to factor VIII.

- Emicizumab prophylaxis reduced the number of bleeds in children with hemophilia A and inhibitors to factor VIII.
- These results build upon data reported from the phase III HAVEN 1 study.

 

 

 

 

 

 

Assembly to Pass New York Health Act Today Single Payer System Guarantees Health Coverage for all New Yorkers


Assembly Speaker Carl Heastie and Health Committee Chair Richard N. Gottfried announced the Assembly's intent to pass the New York Health Act today. The universal "improved Medicare for all" single-payer health plan would cover every New York resident, regardless of wealth, income, age or health status (A.4738, Gottfried).

"While lawmakers in Washington debate giving tax cuts to the wealthy and cutting funding for healthcare for those who need it most, the Assembly Majority remains committed to ensuring every New Yorker has access to the care they need and deserve," said Speaker Heastie. "The Assembly will once again pass this measure, but the recent action taken by Congress to strip more than one million New Yorkers of healthcare has proven it is time for our colleagues in the Senate to act as well."

"The health care system is rigged against working people, and the Trump administration is working to make health care access even worse. New York can do better with an 'improved Medicare for all' single-payer system that covers all of us and is funded fairly," said Assembly Health Committee Chair and bill sponsor Richard N. Gottfried. "Support is growing with the public and in the State Senate, where we now have 30 co-sponsors including all the mainstream Democrats and Independent Democratic Conference. Assembly passage is an important step as we continue to build support for universal health care in the face of the Trump agenda."

For many New Yorkers, the rising cost of healthcare has forced many individuals to make healthcare decisions based on economic factors. Under the New York Health Act, all residents would be eligible to enroll in the universal healthcare system and would have access to the full range of doctors and other healthcare providers. Benefits would include comprehensive inpatient and outpatient care, primary and preventative care, prescription drugs, behavioral health services, laboratory testing, and rehabilitative care, as well as dental, vision, and hearing care.

The publicly funded coverage would include no network restrictions, deductibles or co-pays. Rather than the regressive structure of high premiums, co-pays and deductibles, funding would be based on a shared 80/20 employer/employee contribution system.

Additionally, state funding would be combined with federal funds that are currently received for Medicare, Medicaid and Child Health Plus to create the New York Health Trust Fund. The state would also seek federal waivers that will allow New York to completely fold those programs into New York Health. The local share of Medicaid funding would be ended, offering major property tax relief for New Yorkers.

"The New York State Assembly, once again, shows profound insight into the healthcare needs of the people of New York with passage of New York Health, the single payer bill," said Jill Furillo, RN, NYSNA Executive Director. "We are at a critical juncture as Washington considers new laws that would further entrench the insurance business, setting back patient access to quality, affordable care. But with this vote, the Assembly recognizes that New York is ready to move forward, not backwards, and put in place a system that makes patient need the priority and says no to health insurance gatekeepers. We salute the Assembly and urge the Senate to do the same."

Mario Cilento, President of the New York State AFL-CIO said, "We applaud Speaker Heastie, Assembly Health Committee Chair Gottfried and the Assembly Democratic Majority for continuing the fight to ensure every New Yorker has health care coverage. This is an example of true leadership, particularly at a time when basic health care needs are increasingly under attack due to the uncertainty in Washington."

"Health care is a basic right. Every single New Yorker should have access to quality health care services, regardless of their ability to pay," said NYSUT President Andy Pallotta. "The New York Health plan championed by the Assembly would make us a national leader by providing coverage to every resident of this state. We thank Speaker Heastie, Assembly member Gottfried and the many others who are working so hard to make the New York Health Act a reality."

"As the radical right wing in Washington try to disguise a 500 billion dollar tax cut for the super-rich and insurance giants as a healthcare bill, the New York State Assembly is leading the way with the only kind of healthcare bill that will put people before profits, and make health care what it should be, a human right," said Ivette Alfonso, President of the Citizen Action of New York's Board of Directors. "We commend the Assembly for passing the New York Health Act and implore the IDC/Republican Senate to prove once and for all they are with the people and against Trump."

"Throughout my life, securing and maintaining quality healthcare coverage has been an ongoing struggle and a tremendous source of financial strain," said Elizabeth Rose Huttner, healthcare consumer. Although I am fortunate to come from a financially secure family, the timely passage of the Affordable Care Act kept me from potentially losing insurance coverage due to chronic illness. However, even with the ACA and 'good' insurance through my employer, I was spending $100 a month on co-pays alone and struggling with confusing charges and coverage issues. If the healthcare system failed someone as seemingly fortunate as me, countless others are surely facing catastrophic failures. No one should be faced with these financial challenges simply to live - that is why New York needs the New York Health Act now!"

"As a small business owner for 40 years, I can thank a fellow business person, who helped me organize our state-wide organization, for teaching me KISS (keep it simple stupid). I always search for simple, time and cost effective solutions, because I dislike wasteful bureaucratic systems. In that vein, the New York Health Act seems the only proposal that truly reduces cost for individuals, businesses, local government/taxpayers and doctors. All other plans just seem to shuffle costs around but do nothing to prevent expensive waste," said Peter Looker, business owner.

 

 

 

 

 

 

FDA approves first pill to treat all forms of hepatitis C

This photo provided by Gilead Sciences, Inc. shows the drug Epclusa. Federal health officials on Tuesday, June 28, 2016, approved the first pill to treat all major forms of hepatitis C, the latest in a series of drug approvals that have reshaped treatment of the liver-destroying virus. The Food and Drug Administration approved the combination pill, Epclusa, from Gilead Sciences, for patients with and without liver damage. The new drug's broad indication could make it easier to use than five other hepatitis drugs recently approved by the FDA, which are each tailored to different viral strains or stages of liver disease. (Gilead Sciences, Inc. via APWASHINGTON (AP) — Federal health officials on Tuesday approved the first pill to treat all major forms of hepatitis C, the latest in a series of drug approvals that have reshaped treatment of the liver-destroying virus.

The Food and Drug Administration approved the combination pill, Epclusa, from Gilead Sciences for patients with and without liver damage. The new drug's broad indication could make it easier to use than five other hepatitis drugs recently approved by the FDA, which are each tailored to different viral strains or stages of liver disease.

Gilead's previous two hepatitis drugs have raked in billions of dollars by replacing an older, less effective treatment that involved a grueling pill-and-injection cocktail. But the company's aggressive approach to pricing has drawn scorn from patient groups, insurers and politicians worldwide.

The company said Epclusa will cost $74,760 for a 12-week course of treatment, or roughly $890 per pill. That's less than the initial price for company's previous drug, Harvoni, which cost $1,125 per pill. Gilead's first hepatitis C drug, Sovaldi, cost roughly $1,000 per pill, touching off a national debate about escalating drug costs.

Since 2014, the FDA has approved rival medications from AbbVie Inc., Merck & Co., and Bristol-Myers Squibb Co. that have helped curb prices.

Hepatitis C affects at least 2.7 million people in U.S. and caused more than 19,000 deaths in 2014, according to the Centers for Disease Control and Prevention. The virus develops slowly over decades and many people don't realize they are infected until signs of liver damage emerge, including yellowish skin, dark urine and fatigue. Some develop liver cancer or cirrhosis and require a liver transplant, but many die before a match is available. Baby boomers are five times more likely to have the virus than people in other age groups.

Gilead's new pill combines Sovaldi with a new drug that attacks the virus using a different mechanism. The daily pill can treat all six genetic subtypes of the virus and cures 95 percent of patients in three months, according to clinical trial data reviewed by the FDA. The drug is designed to be used in combination with ribavirin, an older antiviral drug.

The most common side effects with Epclusa included headache and fatigue, according to the FDA.

Although professional medical societies recommend Gilead drugs as first-line treatments for anyone with hepatitis C, a Senate investigation last year found that high costs resulted in less than 3 percent of the potentially eligible Medicaid beneficiaries getting treatment in 2014. Medicaid is the federal-state health program for low-income people.

In 2015, Harvoni was the top-selling prescription drug in the world with over $18 billion in global sales, according to IMS Health. Sovaldi ranked eighth, pulling in $6.6 billion in sales.

Shares of Gilead Sciences Inc., which is based in Foster City, California, rose $4.06, or 5.2 percent, to $82.31 on Tuesday.