Wednesday, March 2, 2022
March PDUFA Dates
The Food and Drug Administration approval calendar was light in February. Nevertheless, the month saw regulatory nods accorded to some breakthrough therapies.
Agios Pharmaceuticals, Inc.'s (NASDAQ:AGIO) Pyrukynd (mitapivat) was approved for the treatment of hemolytic anemia in people with pyruvate kinase deficiency. Hemolysis refers to the destruction of red blood cells.
Pyrukynd is a "new molecular entity," a term that refers to a drug containing an active moiety that hasn't been previously approved by the FDA. NME approval, therefore, is considered a measure of innovation in drug research.
Another NME that passed the FDA hurdle was Sanofi's (NASDAQ:SNY) Enjaymo for the treatment of hemolysis in adults with cold agglutinin disease.
Reata Pharmaceuticals, Inc. (NASDAQ:RETA), as expected, received a complete response letter for its new drug application for bardoxolone methyl as a treatment option for Alport syndrome. An Adcom that met in early December voted against recommending approval of the drug.
PDUFA dates are key "binary or make-or-break catalysts" for biopharma companies. These are dates by which the drug regulator is required to announce its verdict on regulatory applications filed with it, following either a standard review period or priority review.
Bristol-Myers Squibb Seeks Nod For Skin Cancer Combo Therapy
- Company: Bristol-Myers Squibb Company (NYSE:BMY)
- Type of Application: biologic license application
- Candidate: relatlimab and Opdivo
- Indication: melanoma
- Date: March 19
Relatlimab is an antibody, and it's being tested along with Bristol-Myers Squibb's cancer immunotherapy Opdivo, in a fixed-dose combo, as a single infusion for treating adult and pediatric patients with melanoma that has spread and cannot be removed by surgery.
The FDA accepted the company's regulatory application for priority review in September 2021.
Marinus Positive On Seizure Drug Approval
- Company: Marinus Pharmaceuticals, Inc. (NASDAQ:MRNS)
- Type of Application: NDA
- Candidate: ganaxolone
- Indication: seizures
- Date: March 20
Marinus' ganaxolone is an investigational product being developed in intravenous and oral formulations, and it shows both anti-seizure and anti-anxiety activity due to its effects on synaptic and extrasynaptic GABAa receptors.
The FDA accepted for priority review the company's NDA, seeking approval for ganaxolone as a treatment option for seizures associated with CDKL5 deficiency disorder, in September. This is a rare genetic epilepsy.
Marinus management is confident of approval coming through and is expecting no REMS or black box warning on the label, SVB Leerink analyst Marc Goodman said in a mid-February note. The company is looking ahead to a launch timeline of July following the 90-day Drug Enforcement Administration scheduling process.
The company recently announced a delay in the readout from the Phase 3 study of intravenous ganaxolone in refractory status epilepticus, citing omicron impact and an interruption of clinical supply material associated with the drug.
Will Zogenix Gain Label Expansion For Seizure Drug?
- Company: Zogenix, Inc. (NASDAQ:ZGNX)
- Type of Application: supplemental NDA
- Candidate: Fintepla (fenfluramine)
- Indication: seizures
- Date: March 25
Fintepla has already been approved in the U.S. and Europe for treating seizures associated with Dravet syndrome. Zogenix has now applied for expanding the label to include seizures associated with Lennox-Gastaut syndrome, which is rare and difficult to treat childhood developmental and epileptic encephalopathy.
Zogenix has recently announced an agreement to be acquired by Belgian biopharma UCB.
TG Therapeutics Could See A Pushback In Blood Cancer Combo Therapy Review
- Company: TG Therapeutics, Inc. (NASDAQ:TGTX)
- Type of Application: BLA
- Candidate: ublituximab, in combination with Ukoniq (umralisib)
- Indication: chronic lymphocytic leukemia and small lymphocytic lymphoma
- Date: March 25
Ukoniq is currently indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma, who have received at least one prior anti-CD20-based regimen, and for the treatment of adult patients with relapsed or refractory follicular lymphoma, who have received at least three prior lines of systemic therapy.
TG Therapeutics' application seeks approval for ublituximab, an antibody treatment, along with Ukoniq for VLL and SLL. It was accepted for review in May 2021. The company said in November the FDA has notified it regarding a proposed meeting of the Oncologic Drugs Advisory Committee in connection with its review. With still no word on a confirmed date for the Adcom meeting, a decision by the stipulated date is unlikely.
Bristol-Myers Squibb Awaits Third Nod For Reblozyl
- Company: Bristol-Myers Squibb
- Type of Application: sBLA
- Candidate: Reblozyl (luspatercept)
- Indication: anemia in adults with non-transfusion dependent beta thalassemia
- Date: March 27
Reblozyl is an erythroid maturation agent that promotes late-stage red blood cell maturation in animal models. It's being jointly developed by Bristol-Myers Squibb and & Merck & Company, Inc. (NYSE:MRK) in the U.S. Merck received rights to the treatment through its acquisition of Acceleron.
Can Merck Snag Another Approval For Keytruda?
- Company: Merck
- Type of Application: sBLA
- Candidate: Keytruda
- Indication: endometrial carcinoma
- Date: March 28
Merck has filed for getting another regulatory approval for Keytruda, this time as a single agent for the treatment of patients with advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient.
Lipocine Aims To Convert Tlando Tentative Approval To Full Approval
- Company: Lipocine Inc. (NASDAQ:LPCN)/Antares Pharma, Inc. (NASDAQ:ATRS)
- Type of Application: NDA
- Candidate: Tlando (testosterone undecanoate)
- Indication: treating adult males with hypogonadism
- Date: March 28
Tlando is an oral prodrug of testosterone containing testosterone undecanoate, and has received tentative approval from the FDA in December for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism. The final approval was delayed, as the exclusivity period previously granted to Clarus Therapeutics' rival product Jatenzo expires only on March 27.
Lipocine has an exclusive licensing agreement with Antares for marketing Tlando in the U.S.
Akebia Hopes For Positive Tidings On Anemia Drug
- Company: Akebia Therapeutics, Inc. (NASDAQ:AKBA)
- Type of Application: NDA
- Candidate: Vadadustat
- Indication: anemia in chronic kidney disease patients.
- Date: March 29
Akebia and Japanese partner Otsuka Holdings Co., Ltd. (PNK: OTSKY) announced last June that the FDA accepted the NDA filing for vadadustat as a treatment option for anemia due to chronic kidney disease in both adult patients on dialysis and adult patients not on dialysis.
Adcom Calendar
FDA's Peripheral and Central Nervous System Drugs Advisory Committee is scheduled to meet on March 30 to discuss Amylyx Pharmaceuticals, Inc.'s (NASDAQ:AMLX) NDA for sodium phenylbutyrate/taurursodiol powder for oral suspension, for the treatment of amyotrophic lateral sclerosis.
Senate GOP votes to strike Biden's vaccine rule for health care workers
Senate Republicans on Wednesday voted to strike down President Biden’s vaccine mandate targeting health care workers, in a rebuke of the administration.
Senators voted 49-44 to approve the GOP effort to nix the rule — a vote they were able to force under the Congressional Review Act.
Though no Democratic senators voted with Republicans to eliminate the rule, GOP senators were able to get it through the evenly divided Senate because of Democratic absences. Six Democratic senators missed the vote.
The mandate was rolled out by the Centers for Medicare and Medicaid Services, which sought to require the COVID-19 vaccine for health care workers at providers that participate in Medicare and Medicaid.
But the effort to nix the rule is facing headwinds. The Congressional Review Act sets up a fast track process in the Senate, but it does not greenlight the same procedure in the House.
If it made it to Biden’s desk, Democrats expect that he would veto it.
“If it passes this won’t go anywhere in the House, and President Biden would veto it,” a Democratic Senate aide said.
Avoid clinical trial 'valley of death' with medical countermeasure program
The COVID-19 pandemic has put us on notice. It is critical to health and national security for the U.S. to prepare for the inevitable future infectious disease emergencies that will occur. It is clear that vaccines, antivirals, monoclonal antibodies and diagnostics are key components of preparedness and response. And we cannot relent, assuming another coronavirus will ignite the next pandemic. There are other threats out there. The United States needs to launch a strategic effort to create the capability to proactively develop a robust pipeline of products targeted toward the high consequence viral families most likely to cause a pandemic.
While it is impossible to know precisely what the next pandemic pathogen will be — “Disease X” is likely to arise from one of several viral families that include efficiently spreading respiratory viruses some of which may be highly transmissible and lethal. Right now, the U.S. remains vulnerable to the next novel pathogen because there is no sustained federal funding, program or strategy dedicated to accelerating the advanced development of medical countermeasures for such a Disease X virus.
What is stopping government, academia and industry from commencing this important work? The answers are many — the absence of a coordinated government strategy; the scientific complexity of the mission; limited resources; and the lack of a clear commercial market that could drive investment. The list goes on.
There is now hope that Congress will address these impediments. The bipartisan PREVENT Pandemics Act, currently being considered by Congress, directs the National Institutes of Health (NIH) director to develop a ”multidisciplinary research program to advance the discovery and preclinical development of medical products for priority virus families and other viral pathogens with a significant potential to cause a pandemic, through support for research centers.” As part of this program, the NIH director is to partner and coordinate with other agency chiefs.
This is exactly what is needed for early-stage development of medical products for a future Disease X, but it is only one aspect of the multi-stage process.
Stopping at preclinical development of promising products only gets us (almost) halfway there if our national goal is to be optimally prepared for the next threat. As the PREVENT Pandemics Act moves through the legislative process it is imperative that the act includes specific funding and a clear remit to the Biomedical Advanced Research and Development Agency (BARDA) to launch a “Disease X” medical countermeasure development program. Sen. Tammy Baldwin (D-Wis.) introduced a bill, the Disease X Act, last summer that calls for the creation of this program.
Medical countermeasure development is well known to be a high risk undertaking that typically requires significant investment at all stages of development. There are products that make it through preclinical development successfully but falter when it comes to clinical trials and late phase development. Some products and platforms are highly scalable for surge manufacturing, but many are not, and this also must be carefully addressed during this later stage. This chasm between preclinical and clinical development is colloquially referred to as the “valley of death” as products can easily die at this stage.
With biodefense — preparation against potential biological weapons such as anthrax and smallpox — it was quickly realized that unless products were pulled through the “valley of death” the U.S. would be left without any products that could be quickly deployed to mitigate the impacts of a biological attack. Preclinical development would never be enough and because many of these products had no commercial market (as the diseases they addressed are thankfully not everyday occurrences), a comprehensive solution was required.
In 2006, President George W. Bush signed the Pandemic and All Hazards Preparedness Act (PAHPA) which, among myriad other things, established BARDA. BARDA has a mission “to develop and procure medical countermeasures that address the public health and medical consequences of chemical, biological, radiological, and nuclear (CBRN) accidents, incidents and attacks, pandemic influenza, and emerging infectious diseases.”
Specifically, BARDA is an advanced development agency — emphasis on advanced — which bridges across the “valley of death.” As such they have ample experience working with small and large biotech and pharmaceutical companies with promising technologies. These are not early-stage development ideas or basic scientific research. BARDA works with commercial companies of various sizes in a more mature stage of development, while NIH typically works with university-based researchers doing cutting-edge basic science.
To date, BARDA has been integrally involved in the FDA licensure, approval and clearance of over five dozen medical countermeasures. This speaks to their vital role in bringing actual products — against pressing health and biosecurity threats — to fruition. It is the mission they were constituted to fulfill.
BARDA should not be relegated to a junior partner role, cc’d on emails. To advance the national goal of having safe and effective medical products that are ready to be surge produced in the face of a future pandemic, Congress should ensure that BARDA is specifically tasked in the PREVENT Pandemics Act with executing an advanced development program for Disease X medical countermeasures so that they aren’t interminably mired in the “valley of death” when the next infectious disease emergency surfaces.
Amesh Adalja, M.D., is an infectious disease physician and a senior scholar at the Johns Hopkins Center for Health Security.
Anita Cicero, JD is deputy director at the Johns Hopkins Center for Health Security and a senior scientist at the Johns Hopkins Bloomberg School of Public Health.
Urban Institute: Part D $2,000 out-of-pocket cost cap would benefit less than 1M seniors
A proposal to cap Medicare Part D drug costs would benefit nearly 1 million seniors, according to a new study.
The study, released Tuesday by the Robert Wood Johnson Foundation, comes as Congress is attempting to salvage drug pricing reforms before the midterm elections. One of the proposals being floated has been a $2,000 cap on out-of-pocket prescription drug costs on Part D beneficiaries that don’t already qualify for cost-sharing protections.
If the cap is put in place, it would benefit more than 860,000 seniors, the study conducted by the think tank Urban Institute found. Medicare drug spending would also increase by less than 1%.
“Ultimately, a spending cap would enhance the overall benefit of the Medicare Part D program without substantially raising Medicare program spending,” said Anuj Gangopadhyaya, senior research associate at Urban Institute, in a statement.
Urban’s researchers used a simulation model to estimate Medicare and out-of-pocket spending on Part D in 2019. It estimated there were about 866,000 Part D enrollees that year who did not get low-income subsidies to help cover the costs of drugs.
It found Part D enrollees had average total drug expenditures of about $19,800, and $2,900 would be spent out-of-pocket by the beneficiary.
Certain enrollees would also benefit more from the cap based on their expenses. For instance, 40% of beneficiaries who had out-of-pocket costs above $2,000 spent up to $2,500. Another 30% spent between $2,500 and $3,000.
There were 18% that spent more than $3,500 in out-of-pocket costs.
The study comes as Congress is trying to figure out a path forward on drug price reform ahead of the 2022 midterms.
A $2,000 cap on out-of-pocket Part D costs was included in the Build Back Better Act, a major $1.75 trillion social spending package that passed the House earlier this year. The legislation, however, has stalled in the Senate due to objections from Sen. Joe Manchin, D-West Virginia.
However, Democrats are now trying to figure out which pieces of drug price reform could survive in a slimmed-down package this year.
“The cap and other drug provisions could remain in a potential slimmed-down budget reconciliation bill that might pass in both the House and the Senate,” Urban’s study said.
Another potential reform could be placing a cap on Part D drug costs that would prevent drug companies from hiking prices beyond the cost of inflation.
IsoRay therapy has favorable outcomes in prostate cancer
Investigators from the University of Pittsburgh School of Medicine have published a clinical study demonstrating favorable outcomes for localized intermediate-risk prostate cancer patients treated with IsoRay Inc's
(Get Free Alerts for ISR) Cesium-131 brachytherapy known as Cesium Blu.- Brachytherapy is a localized internal radiation therapy in which seeds, ribbons, or capsules containing a radiation source are placed in or near the tumor.
- The study analyzed the outcomes for 335 intermediate-risk prostate cancer patients treated with Cesium-131 brachytherapy.
- Study patients had significant follow-up time.
- The study found that both the "favorable" (147 patients) and "unfavorable" (188 patients) intermediate-risk groups demonstrated excellent biochemical outcomes.
- Those outcomes were 97.6% and 91.4%, respectively, at five years. For 135 "favorable" patients treated with Cesium-131 implant alone, the outcome was 98.1%.
- Investigators used Cesium-131 to decrease the duration of acute toxicity compared to other radioisotopes because of its shorter half-life.
REGENXBIO 2021 Financial Results and Recent Operational Highlights
Closed eye care collaboration agreement with AbbVie to develop and commercialize RGX-314
Continue to advance RGX-314 program for the treatment of wet AMD and diabetic retinopathy
Received IND clearance and Orphan Drug Designation for RGX-202 for the treatment of Duchenne
Presented positive data from RGX-121 and RGX-111 clinical trials for the treatment of MPS II and MPS I
$849 million current cash and cash equivalents of as of December 31, 2021; including upfront payment from closing of the AbbVie eye care collaboration agreement; operational runway into 2025
Conference call Tuesday, March 1st at 4:30 p.m. ET
Financial Guidance
Based on its current operating plan, REGENXBIO expects its balance in cash, cash equivalents and marketable securities of $849.3 million as of December 31, 2021 to fund its operations, including the completion of its internal manufacturing capabilities and clinical advancement of its product candidates, into 2025.
Conference Call
In connection with this announcement, REGENXBIO will host a conference call and webcast today at 4:30 p.m. ET. To access the live call by phone, dial (855) 422-8964 (domestic) or (210) 229-8819 (international) and enter the passcode 7635958. To access a live or recorded webcast of the call, please visit the "Investors" section of the REGENXBIO website at www.regenxbio.com. The recorded webcast will be available for approximately 30 days following the call.
https://finance.yahoo.com/news/regenxbio-reports-fourth-quarter-full-210500073.html