Shares of Madrigal Pharmaceuticals (MDGL) are sliding in pre-market trading after the company’s competitor, Viking Therapeutics (VKTX), announced top-line results from a Phase 2 study of VK2809, its novel liver-selective thyroid receptor beta agonist, in patients with non-alcoholic fatty liver disease, or NAFLD, and elevated low-density lipoprotein cholesterol, or LDL-C. The study successfully achieved its primary endpoint, with patients receiving VK2809 demonstrating statistically significant reductions in LDL-C compared with placebo. In addition, the trial’s secondary endpoint was achieved, with VK2809-treated patients experiencing statistically significant reductions in liver fat content compared with placebo. Citi analyst Joel Beatty recently started Madrigal with a Buy rating and $340 price target, telling investors that the company’s MGL-3196 appears to be the favorite among four non-alcoholic steatohepatitis drugs in late stage development. In pre-market trading following Viking’s announcement, Madrigal shares are down $33.83, or roughly 15%, to $194.60
Tuesday, September 18, 2018
Monday, September 17, 2018
Antimicrobial resistance: FDA discusses reimbursement reforms
Reimbursement reforms for antimicrobial treatments could include “a mix of milestone payments and subscription fees for developers of FDA-approved products with high economic and clinical value, targeted at multi-drug resistant organisms and linked to proven clinical outcomes,” FDA Commissioner Scott Gottlieb said in a speech at Pew Charitable Trusts on Friday.
He also offered the idea of using a “subscription-based model” that could see hospitals paying a flat rate for access to a certain number of doses of a new antimicrobial.
Currently, the Centers for Disease Control and Prevention (CDC) estimates that the direct cost of antimicrobial resistance on the US economy is $20 billion annually.
“These subscription fees could be priced at a level to create a sufficient return on the investment to develop drugs with a certain profile,” Gottlieb said. “This should have the effect of creating a natural market for drugs that meet certain important specifications.”
“These subscription fees could be priced at a level to create a sufficient return on the investment to develop drugs with a certain profile,” Gottlieb said. “This should have the effect of creating a natural market for drugs that meet certain important specifications.”
The FDA is also discussing payment pilots with other federal agencies, including the Centers for Medicare and Medicaid Services (CMS), noting interest in doing such pilots in concert with the private sector as well.
New approaches to reimbursement that could be explored might “also include new technology add-on payments for certain new antibacterial drugs that meet critical patient and public health needs,” he said.
Meanwhile, earlier this week, the FDA released a new request for information (RFI) to obtain external input into developing an annual list of regulatory science initiatives specifically for antimicrobial products. Part of such a list will be a focus on the “delay in availability of information regarding the identification and antibacterial susceptibility of the causal pathogen, when isolated.”
Responses to the RFI will be accepted until 31 October 2018.
New Medicare Advantage tool to lower drug prices crimps patients’ choices
Under the new rules, these private Medicare insurance plans could require patients to try cheaper drugs first. If those are not effective, then the patients could receive the more expensive medication prescribed by their doctors.
Insurers use such “step therapy” to control drug costs in the employer-based insurance market as well as in Medicare’s standalone Part D prescription drug benefit, which generally covers medicine purchased at retail pharmacies or through the mail. The new option allows Advantage plans—an alternative to traditional, government-run Medicare—to extend that cost-control strategy to these physician-administered drugs.
In traditional Medicare, which covers 40 million older or disabled adults, those medications given by doctors are covered under Medicare Part B, which includes outpatient services, and step therapy is not allowed.
About 20 million people have private Medicare Advantage policies, which include coverage for Part D and Part B medications.
Some physicians and patient advocates are concerned that the pursuit of lower Part B drug prices could endanger very sick Medicare Advantage patients if they can’t be treated promptly with the medicine that was their doctor’s first choice.
Critics of the new policy, part of the administration’s efforts to fulfill President Donald Trump’s promise to cut drug prices, say it lacks some crucial details, including how to determine when a less-expensive drug isn’t effective.
Medicare Advantage insurers spend about $12 billion on Part B drugs, compared to the $25.7 billion traditional Medicare spent in 2016 on such drugs. Insurers that adopt the step therapy policy can apply it only to new prescriptions—medicine a patient hasn’t received in the past 108 days.
The change in policy gives insurers a new bargaining tool: Pharmaceutical makers may want to compete by cutting prices to get their product on the plans’ list of preferred lists, allowing patients to receive the medicines without step therapy pre-conditions. That “strengthens their negotiating position with the manufacturers,” Centers for Medicare & Medicaid Services chief Seema Verma said when she unveiled the policy last month.
It could also save patients money because they usually pay a portion of the Part B prescription cost. In addition, Medicare is requiring plans to share the savings with enrollees.
“Competition is a big factor in price concessions,” said Daniel Nam, executive director of federal programs at America’s Health Insurance Plans, an industry trade group. But insurers haven’t had much leverage to negotiate lower prices for these drugs without strategies like step therapy, he said.
Federal health officials told insurers in a memo last month they could substitute a less expensive Part B drug to treat a medical condition the FDA has not approved it for, if insurers can document that it is safe and effective. Yet coverage for a Part D drug is usually denied for a condition that doesn’t have FDA approval, according to the Center for Medicare Advocacy, which helps beneficiaries with appeals.
Several representatives of medical specialty groups recently met with Alex Azar, the secretary of the Department of Health and Human Services, to express their concerns.
Dr. Stephen Grubbs, vice president of clinical affairs at the American Society of Clinical Oncology, was among them. He said Azar told then the new step therapy policy would not have a big impact on cancer treatment.
Patients and their physicians who encounter problems getting specific Part B drugs can appeal using the “process that we have throughout the Medicare Advantage program and Part D plans,” advised Verma.
Under this system, if patients don’t want to follow their insurance plans’ requirements to try a less-expensive medication first, they can request an exception to step therapy.
“They need their doctor’s support,” said Francine Chuchanis, director of entitlement rights at Direction Home, an Area Agencies on Aging organization that serves older adults and people with disabilities in northeastern Ohio. The physician must tell the plan why its restrictions should be lifted and provide extensive documentation.
The plans have 24 hours to respond to an expedited exception request and 72 hours for a regular one. During this time, “people are going without their drugs,” said Sarah Jane Blake, a Medicare counselor for New York’s StateWide Senior Action Council.
However, Dr. David Daikh, president of the American College of Rheumatology, said plans frequently do not meet the 72-hour deadline.
“We raised this point with the secretary and his staff,” he said. “They replied that they felt that there would not be a backlog for this program.”
If a plan denies the exemption, patients can file a “reconsideration” appeal. During this process, patients still can’t get their medicine unless they pay for it out-of-pocket.
Only a tiny fraction of Medicare Advantage beneficiaries filed a reconsideration appeal last year. Of the 3,498 cases that were decided, just 1 in 10 beneficiaries won decisions fully or partially in their favor, according to Medicare statistics.
“That’s disheartening to say the least,” said Blake, but she wasn’t surprised. “Beneficiaries are intimidated by the hoops they have to go through and often give up trying to purchase the drugs prescribed for them.”
Genentech and Hemophilia Patients Eye Oct. 4 for Hemlibra Ruling
Hemophilia patients could have an easier time taking their medication if the U.S. Food and Drug Administration (FDA) gives the green light for the newest formulation of Genentech’s Hemlibra.
The FDA set a PDUFA deadline of Oct. 4 for a subcutaneous formulation of the hemophilia treatment.
Dr. Mike Callaghan, one of Genentech’s Hemlibra researchers, said this formulation will make it easier for hemophilia patients to self-administer the treatment. Most hemophilia drugs are intravenous, but Callaghan said a lot of hemophilia patients have difficulty finding a vein they can use to administer the treatment. If approved, the new formulation of Hemlibra would be a powder that would be mixed with saline. A small needle would allow it to be injected under the skin. With this, he said patients will not have to worry about missing a vein.
“Being subcutaneous is a big advantage,” Callaghan told BioSpace. “It makes it a lot easier.”
Not only is the newest formulation of Hemlibra easier to administer, but Callaghan also said its half-life is longer than most hemophilia treatments. Current products have half-lives of hours and require an infusion about every three days. Callaghan said the new formulation of Hemlibra has a half-life of 28 days and can be administered weekly or a couple of times per week. That longer half-life will allow for a better dosing regimen and will likely facilitate greater patient adherence. When hemophilia patients do not adhere to their dosing schedules, they can experience more frequent bleeds, Callaghan said.
“It’s easier to use, easier to be compliant with and has better outcomes,” Callaghan said of the new Hemlibra. He added that the drug will improve the quality of life for hemophilia patients.
That impact on quality of life is something Genentech has been aiming at achieving with its hemophilia products. Last year Dr. Gallia Levy, head of Hemlibra research at Genentech, told BioSpace that the less frequent dosing will help improve quality of life for patients. Patients being able to go weeks without needing an infusion will have a new lease on life, Levy said in December, following the American Society of Hematology meeting.
Earlier this year Genentech unveiled late-stage results from Hemlibra trials that showed shows the drug significantly reduced treated bleeds in a broad patient population in two separate studies. In the HAVEN 3 study people with hemophilia A without factor VIII inhibitors who received Hemlibra (emicizumab-kxwh) prophylaxis every week or every two weeks showed a 96 percent reduction and 97 percent reduction in treated bleeds, respectively. That testing was against no prophylaxis. Additionally, the data from the late-stage trials showed 55.6 percent of patients treated with Hemlibra every week and 60 percent who were treated every two weeks experienced zero treated bleeds, compared to 0 percent of people treated with no prophylaxis.
With those positive results and the benefits that trial patients have seen with Hemlibra, Callaghan said approval of this formulation will be a “game changer” for patients. It’s a significant boost over factor XIII replacement, which is the standard of care.
Hemlibra was first approved in November 2017 by the U.S. Food and Drug Administration. It was the first medication approved in 20 years for Hemophilia A with inhibitors. If the FDA approves this latest indication, it will benefit those hemophilia patients who do not have inhibitors, Callaghan said. The larger group of hemophilia patients don’t have inhibitory antibodies and will be a wider group of patients for the approval, he said. With expanded approval, analysts predict that Hemlibra could generate up to $5 billion annually for the Roche subsidiary.
Fate Collaborates with ONO on Off-the-Shelf CAR-T Cell Cancer Immunotherapy
Fate Therapeutics, Inc.(NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced today that it has entered into a collaboration with ONO Pharmaceutical Co., Ltd. for the joint development and commercialization of two off-the-shelf CAR-T cell product candidates. Using Fate Therapeutics’ proprietary induced pluripotent stem cell (iPSC) product platform, the two CAR T-cell collaboration candidates will each be derived from a clonal master iPSC line engineered to completely eliminate endogenous TCR expression, insert a chimeric antigen receptor (CAR) into the TRAC locus and incorporate other anti-tumor functionality. This transformative approach enables the cost-effective production of cell-based cancer immunotherapies that are uniformly engineered, extensively characterized and homogeneous in composition, and can be consistently and repeatedly mass produced and delivered to patients in an off-the-shelf manner.
“We are delighted to collaborate with ONO, a global leader in oncology with a long history of developing innovative breakthrough cancer drugs,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “This partnership with ONO enables Fate to further enhance its expertise in targeting solid tumors and to accelerate the global development of our pipeline of off-the-shelf, iPSC-derived CAR-T cell product candidates.”
Under the terms of the strategic option agreement, Fate Therapeutics and ONO will jointly advance each iPSC-derived CAR-T cell collaboration candidate to a pre-defined preclinical milestone. The first iPSC-derived CAR T-cell candidate targets an antigen expressed on certain lymphoblastic leukemias, and Fate Therapeutics retains global responsibility for development and commercialization with ONO having an option to assume responsibilities in Asia. The second candidate targets a novel antigen identified by ONO expressed on certain solid tumors, with ONO having an option to assume global responsibility for further development and commercialization and Fate Therapeutics retaining the right to co-develop and co-commercialize the candidate in the United States and Europe. For both collaboration candidates, Fate Therapeuticsretains manufacturing responsibilities on a global basis.
“ONO identified Fate Therapeutics as the partner of choice for the generation of off-the-shelf CAR T-cell cancer immunotherapies in our portfolio,” said Hiromu Habashita, Corporate Officer, and Executive Director of Discovery & Research of ONO. “We are excited to work with Fate Therapeutics and apply its industry-leading iPSC product platform to develop and deliver the next-generation of CAR T-cell therapies for cancer patients.”
Fate Therapeutics will receive an upfront payment and committed research funding during the preclinical option period, and is eligible to receive a preclinical option exercise fee, clinical, regulatory and commercialization milestone payments and tiered royalties on net sales by ONO in connection with the development and commercialization of each collaboration product by ONO in the ONO territory.
Ionis: Potential breakthrough Huntington’s med to advanced trial
A potential breakthrough drug for treating Huntington’s disease from Carlsbad’sIonis Pharmaceuticals will begin an advanced clinical trial early next year. If successful, the trial could lead to marketing approval.
Ionis partner Roche, which is handling the clinical trials, made the announcement Sunday. The trial will take place globally.
Huntington’s disease is an incurable and invariably fatal neurodegenerative disease caused by mutations in one gene. More than 30,000 Americans have the mutation, and either have the disease or will eventually develop it.
The age of onset varies with the mutation’s severity. Most often, symptoms appear in middle age. These include uncontrollable movements and problems with emotions and cognition, along with changes in personality. In advanced cases, patients have trouble speaking or swallowing.
Existing treatments only manage symptoms. There is no treatment that stops or even slows down the disease’s progression.
The mutation causes production of an abnormal form of a protein called huntingtin, which is essential for brain development. It is genetically dominant, meaning that only one copy of the gene, inherited from either parent, causes Huntington’s.
The drug, RG6042, (originally IONIS-HTTRx) inhibits production of the mutant huntingtin. It uses an Ionis technology called antisense, which blocks or changes genetic activity. All Ionis drugs use antisense.
Inhibiting production of the protein in theory should slow, stop or even reverse the disease. Early clinical testing has shown that the drug does inhibit huntingtin production and provided preliminary evidence of some benefit. But efficacy can only be proven by the more advanced trial.
Success “would be a historic moment for Huntington’s disease patients, their loved ones and the health care providers who treat and take care of HD patients,” said C. Frank Bennett, senior vice president of research at Ionis, in a statement. “It also would be an important advance for the neurodegenerative field in general.”
Ionis has already successfully developed a drug effective against another previously untreatable neurological disease, spinal muscular atrophy, which in its severest form can kill in infancy. Called Spinraza, it’s sold by partner Biogen.
Ionis is also developing drugs for Alzheimer’s and ALS, two other incurable and fatal neurodegenerative diseases.
Ionis developed RG6042 in collaboration with researchers from the lab of Don W. Cleveland at UC San Diego. It is injected into the spinal fluid, enabling it to reach the brain. Roche licensed the drug last December, assuming the lead in development.
The trial will be double-blinded, meaning that neither doctors nor patients will know who is getting the drug and who is getting a placebo. The drug — or placebo — will be given to up to 660 patients manifesting Huntington’s symptoms over 25 months, Roche said in its announcement. They will be treated at about 80 to 90 sites worldwide.
More information on the upcoming Phase 3 trial once it gets underway, along with trials of other Huntington’s drugs, can be found at http://www.hdtrialfinder.org and http://www.clinicaltrials.gov. In addition, Kenneth Serbin, a San Diegan who carries the mutation, writes about Huntington’s at http://curehd.blogspot.com.
Goldman Life Science Pair Trade: Buy Agilent, Sidelines On Thermo Fisher
Goldman Sachs has a pair trade in the life sciences tools and diagnostics space ahead of third-quarter earnings season.
The Analyst
Analyst Patrick Donnelly maintained a Buy rating on Agilent Technologies Inc A 0.33% and increased the price target from $77 to $82.
The analyst added Agilent to Goldman’s Americas Conviction List and also named it as a top pick.
At the same time, Donnelly downgraded shares of Thermo Fisher Scientific Inc. TMO 1.45% from Buy to Neutral and maintained a $250 price target.
The analyst removed the stock from the Americas Conviction List.
The Thesis
Both Agilent and Thermo Fisher have sound fundamentals and are poised for “beat-and-raises” over the next several quarters, Donnelly said in a Monday note. (See his track record here.)
Donnelly said he prefers Agilent’s setup and views Thermo Fisher’s growth acceleration and margin expansion as being priced into the stock.
Agilent: A Premium Growth Story In Tools
Agilent is a premium growth story in tools on the basis of its ability to accelerate organic growth heading into 2019 despite concerns about China trade headwinds, Donnelly said. China accounts for about 20 percent of the company’s revenues, he said.
Agilent has a clean path to growth in the fourth quarter and in 2019 amid support from “continued momentum in CrossLab, Intuvo/Ultivo product cycle ramps, a rebound in China food and environmental orders and the expansion of the Oligo facility,” the analyst said.
Intuvo and Ultivo should be key drivers over the next 12-24 months, with the former expected to make meaningful contributions in 2019, potentially adding about 1 percent to organic growth in 2019 and 2020, Donnelly said.
“We continue to see valuation for Agilent as undemanding and see upside for multiple expansion as investors turn to the layering of organic growth drivers.”
Thermo Fisher’s Setup Becomes More Demanding
There is limited upside to Goldman’s price target for the shares of Thermo Fisher, as the stock’s valuation already reflects the prospects for organic growth acceleration, Donnelly said.
“While we remain constructive on the fundamental story for TMO, we prefer to remain on the sidelines, as the setup over the next year gets more demanding driven by more normalized top-line impacts from FEI.”
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