Gilead Reports Positive Results from Hepatitis Drug Trial

 Gilead Sciences Inc. said Thursday that the latest clinical trial evaluating the antiviral medication Hepcludex for the treatment of chronic hepatitis delta virus showed significant viral declines at 48 weeks.

The company said the study's findings underscore the efficacy and safety of Hepcludex, the brand name for the first-in-class entry inhibitor bulevirtide, for treating chronic HDV.

At week 48, study participants treated with bulevirtide monotherapy achieved a greater combined virological and biochemical response than those that weren't treated with bulevirtide.

The data demonstrates a positive impact of bulevirtide on patient-reported outcomes and reinforces the clinical utility of bulevirtide as a monotherapy for chronic HDV, which currently has no other approved treatment options, Gilead said.

The safety profile of the medication at week 48 was consistent with prior reports, with no participants having an adverse reaction that led to discontinuation of the treatment.

https://www.marketscreener.com/quote/stock/GILEAD-SCIENCES-INC-4876/news/Gilead-Reports-Positive-Results-from-Hepatitis-Drug-Trial-40798405/

Sarepta Duchenne Therapy Update

 Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on SRP-5051 (vesleteplirsen), the Company’s next-generation peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) to treat patients with Duchenne muscular dystrophy who are amenable to exon 51 skipping. The hold in Part B of Study 5051-201, also known as MOMENTUM, follows a serious adverse event of hypomagnesemia. FDA is requesting information on all cases of hypomagnesemia, including a small number of non-serious grade 2 cases, and to assess the adequacy of the risk mitigation and safety monitoring plan. In the next few days we will respond to the Agency with this information and proposed changes to the monitoring plan.

“Patient safety is always our top priority. The hypomagnesemia was identified through lab tests conducted as part of the monitoring outlined in the protocol of the MOMENTUM study and is similar to previously observed cases of hypomagnesemia in clinical trials of SRP-5051. The hypomagnesemia was transient and patients’ magnesium levels returned to normal following additional supplementation,” said Louise Rodino-Klapac, Ph.D., executive vice president and chief scientific officer, Sarepta Therapeutics. “Globally, we have enrolled approximately half of the planned patients in Part B of MOMENTUM. The study is ongoing, and we remain on track to complete enrollment by the end of the year. We will work to share information with FDA with the goal of resuming screening and dosing in the U.S. as quickly as possible.”

Sarepta will host an investor conference call on Thurs., June 23, 2022 at 4:15 pm Eastern time, to discuss this update. The presentation will be webcast live under the investor relations section of Sarepta's website at https://investorrelations.sarepta.com/events-presentations and archived there following the call for one year. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary. The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 6055778. Please specify to the operator that you would like to join the "SRP-5051 Program Update."

https://www.marketscreener.com/quote/stock/SAREPTA-THERAPEUTICS-INC-11204214/news/Sarepta-Therapeutics-Provides-Update-on-SRP-5051-for-the-Treatment-of-Duchenne-Muscular-Dystrophy-40800981/

New nicotine limits will only increase harm

 Just one month after publishing a rule to ban menthol cigarettes, President Biden intends to force tobacco companies to reduce cigarette nicotine content. Lower nicotine content in cigarettes can quickly be expected to increase cigarette consumption.  

Why? Nicotine is a highly addictive, but relatively harmless substance, much like caffeine. Nicotine itself does not cause cancer, heart disease, or lung disease. More than 7,000 other chemicals in cigarettes and cigarette smoke cause those illnesses. It is ridiculous to seek a limit on nicotine, the least dangerous of these ingredients.

Michael Russell, one of the first researchers to identify nicotine as the primary reason smokers became addicted, is often quoted as saying, “people smoke for the nicotine, but they die from the tar.” If President Biden gets his way, people will be forced to smoke more cigarettes to get the nicotine they crave. Someone who typically smokes one pack a day would now need two, or even three, packs of deadly cigarettes to meet their addiction. That’s a lot more tar. 

This would also mean that people addicted to cigarettes would spend more of their hard-earned money buying cigarettes. Let’s not forget that this administration spent months denying and downplaying rampant inflation, which hurts the poor more than it hurts the rich. While inflation might not bother the President or the D.C. elites who give him advice, the average American struggles to fill their car with gas and put food on their table. Considering 72 percent of cigarette smokers come from low-income communities, this proposal comes at the cruelest possible time.  

In New York, those in the highest income groups spend only 2 percent of their annual income on cigarettes. In contrast, those in lower-income groups spend nearly 25 percent of their income on cigarettes. President Biden is embracing the role of a sick, twisted Robin Hood who takes from the poor and gives to the rich, all in the name of “public health.” While the Biden administration may think they are sticking it to Big Tobacco by limiting nicotine content, this decision will increase cigarette sales and lead to more illness and death. 

Not only would this proposal have public health and economic ramifications, but it would also weaken America’s national security. As we have seen from past prohibitions, banning products does not reduce demand. Instead, it offers criminals the opportunity to profit. Tobacco smuggling is primarily run by highly organized and highly dangerous international crime syndicates. The profits these criminal groups make from tobacco smuggling are used to fund human trafficking, money laundering and even terrorism. Limiting nicotine in cigarettes would energize these criminals and make America a less safe place to live and work. 

This is also a classic example of the president exceeding his authority. By pushing this proposal through the Food and Drug Administration, where the public has little to no say, the president is making it clear that he couldn’t care less what Americans think of his decisions. It’s a lot easier to convince life-long bureaucrats to go along with bad decisions than Congress and the American people who elect them. 

Addiction is not a choice but making life more expensive for people who use tobacco products is a choice. At a time of great economic uncertainty, making survival more difficult for those who are barely hanging on is unwise. The Biden administration is playing politics with our national security and the lives of millions of Americans. 

Karl Abramson is a consumer issues fellow at Americans for Tax Reform.

https://thehill.com/opinion/healthcare/3532823-counterproductive-federal-nicotine-limits-will-only-increase-harm/

FDA’s accelerated drug approval process needs another look

 It was precisely 30 years ago, in 1992, that the Food and Drug Administration (FDA) established the Accelerated Approval Program (AAP) in response to the HIV epidemic.

The AAP is a mechanism that permits conditional approval of a new drug that treats a serious medical condition and fills an unmet need based on its impact on a surrogate end point.  

A surrogate end point, i.e., a biomarker, may be a laboratory measure, a radiographic image, a physical sign or any measure that is presumed to predict clinical benefit but is not independently a measure of clinical improvement. To qualify, the end point must be considered likely to correlate with clinical improvement. If approved under this mechanism, the drug will need to be tested in larger, more definitive clinical trials, so-called phase 4 trials, using end points that demonstrate benefit within a few years. If these trials are inconclusive, the approval may be withdrawn. 

Today, the FDA approves more drugs through this and other related fast-track mechanisms than the traditional route. Approximately 75 percent of the drugs currently greenlighted by the FDA participated in at least one special program designed to speed up the review process. 

The AAP has had a positive impact on HIV and cancer chemotherapy, and it is estimated that more than 300 drugs have been approved through this pathway. The point of concern is that the surrogate end point, the scientific basis of the approval, does not always predict clinical utility. In the case of HIV, CD 4 counts – white blood cells that fight infection – and HIV viral load serve as reliable predictors of clinical response. In the cancer space, the ability of end points to predict clinical utility has been mixed with reports indicating that only one-fifth of drugs approved based on surrogate end points improve survival rates in confirmatory trials.  

Post approval confirmatory monitoring has been inconsistent. These drugs, at times, stay on the market despite failure to convincingly demonstrate efficacy in phase 4 trials as “dangling approvals,” drugs for which prior authorization continues in spite of lack of clinical efficacy. In the interim, they cost the public billions of dollars and raise unrealistic expectations for treatment.  

Further, all biomarkers are not the same. As we move from infectious diseases and cancer to the realm of degenerative brain disorders, the relationship of biomarkers to clinical response becomes increasingly murky. The recent debacle surrounding the approval of Aduhelm for the treatment of Alzheimer’s disease under this mechanism is a good example of the slippery slope in biomarker science resulting in premature approval. In this case, the “original sin” was the approval based exclusively on the drug’s ability to lower levels of amyloid, a putative biomarker of the disease, in the brain despite the fact that substantially lowering amyloid levels did not correlate with clinical improvement.  

Fortunately, the Centers for Medicare & Medicaid Services (CMS), after looking at the data more objectively, approved coverage only for patients enrolled in federally approved clinical trials. In this instance, society dodged a bullet and the checks and balances in our system worked.

After spending decades developing compounds that lower amyloid levels in the brain to treat Alzheimer’s, the pharmaceutical industry is moving on to molecules and pathways other than amyloid. Biomarkers have a potentially important role to play in this regard. In the early phases of clinical trials, they can serve to identify promising drugs that are safe and target specific. Perhaps more importantly, early trials should unequivocally establish a link between biomarkers and meaningful clinical end points that can then be used in more definitive phase 3 trials that compare the drug with a placebo — the international gold standard in clinical trials. 

The AAP was established 30 years ago and was designed to accelerate drug approval in select, life threatening cases where the standard approval process was too long and cumbersome. But it was predicated on the assumption that the surrogate end point would be demonstrably linked to relevant clinical outcome measures. As the link between the surrogate marker and clinical outcomes becomes more tenuous, the process falls apart and becomes a mechanism for an end run around the regulatory pathway. Enthusiasm and expediency should not replace scientific objectivity. 

Congress is poised to give the FDA more resources to monitor late phase 4 trials after drugs receive preliminary approval under the accelerated program. That is necessary but not sufficient to correct the situation. Once a drug receives preliminary approval, close monitoring and a subsequent recall are more difficult to implement. One of the FDA’s primary responsibilities is to ensure that human and veterinary drugs, vaccines and other biological products and medical devices intended for human use are safe and effective. 

The FDA should scrutinize the accelerated program rigorously to ensure that surrogate end points are clinically meaningful before approving drugs under this mechanism. The goal of drug therapy is to treat the disease — and not surrogate markers without impacting the disease. The FDA should live up to expectations and its original mandate. 

Anand Kumar, MD, MHA is a professor and head of the department of psychiatry at the University of Illinois at Chicago and past president of the American Association for Geriatric Psychiatry. 

https://thehill.com/opinion/healthcare/3533622-expediency-v-efficacy-reexamining-the-fdas-accelerated-drug-approval-process/

NYC makes vaccines available to residents possibly exposed to monkeypox

 The New York City Department of Health and Mental Hygiene on Thursday abruptly announced it would be offering vaccines to New Yorkers who may have been exposed to monkeypox.

In a statement, the department said adult men who have sex with men and have had sex with multiple or anonymous partners in the past 14 days will be eligible to receive smallpox vaccines believed to also be effective against monkeypox.

The vaccine being made available to New Yorkers is the Jynneos smallpox vaccine, administered in two doses four weeks apart. The doses will be administered at the Chelsea Sexual Health Clinic, which will be open Sunday through Thursday from 11 a.m. to 7 p.m.

According to the most recent data from the Centers for Disease Control and Prevention (CDC), over 150 monkeypox cases have been confirmed across 24 U.S. states and territories. New York has confirmed 22 cases so far.

As other health authorities have repeatedly stressed throughout the recent outbreak, the New York State Department of Health said anyone can contract monkeypox, though the virus has largely spread through social networks of gay and bisexual men.

“Men who have sex or other intimate contact with men they met through dating apps or social media platforms, or at clubs, raves, sex parties, saunas, or other large gatherings may be at higher risk of having been recently exposed,” the department said.

Limited walk-ins to receive vaccines will be accepted, but appointments — which can be made here — are preferred. As of Thursday afternoon, no appointments are available.

“As I have said since day one, we are prepared, not panicked and this monkeypox vaccination site is one more critical tool to keep New Yorkers healthy,” New York City Mayor Eric Adams (D) said.

Not long after the announcement was made, an extremely long line appeared to have formed at the clinic. A photo shared by New York Times religion correspondent Liam Stack on Twitter showed a line of men leading out of the clinic.

Manhattan Borough President Mark Levine, who is also a former New York City Council member, said on Twitter that there were only 1,000 vaccine doses, which he referred to as “far, far too little.” Levine called on the federal government to expand New York’s allocation of vaccine doses “ASAP.”

The Hill has reached out to the New York City Department of Health and Mental Hygiene for further comment on the vaccine rollout for monkeypox.

https://thehill.com/policy/healthcare/3534713-nyc-makes-vaccines-available-to-residents-possibly-exposed-to-monkeypox/

Timber Pharma Starts Phase 3 Trial Evaluating TMB-001 in Congenital Skin Condition

 Timber Pharmaceuticals, Inc. ("Timber" or the “Company”) (NYSE American: TMBR), a clinical-stage biopharmaceutical company focused on the development and commercialization of treatments for rare and orphan dermatologic diseases, today announced that the first four patients have been enrolled in the pivotal Phase 3 ASCEND clinical trial.  ASCEND will evaluate the efficacy, pharmacokinetics and safety of TMB-001 0.05%, a topical isotretinoin formulated using the Company’s patented IPEG™ delivery system, for the treatment of moderate to severe forms of congenital ichthyosis (CI).

The U.S. Food & Drug Administration (FDA) awarded a $1.5 million grant through its Orphan Products Clinical Trials Grant program to support completed Phase 2a and Phase 2b clinical trials that evaluated TMB-001. The FDA also granted Breakthrough Therapy and Fast Track designations to TMB-001. Leading research centers in the U.S., Canada, Italy, France, and Germany are participating in the ASCEND study. The first patients were enrolled by Kenneth Dawes, M.D., and his research team at the Dawes Fretzin Dermatology Group in Indianapolis, Indiana.

“We are pleased to launch the pivotal ASCEND study and enroll the first patients, which brings us one step closer to delivering an important new treatment option for people who are burdened by the life-long endeavor of managing CI,” said John Koconis, Chairman and Chief Executive Officer of Timber. “Many dermatologists may be familiar with oral isotretinoin and its effectiveness as a treatment for CI, but they are also aware of the systemic toxicity associated with oral therapy. We believe that TMB-001 has the potential to deliver significant efficacy and relief to patients while minimizing systemic absorption, thereby lowering the rates of side effects seen with the oral compounds. Our patented topical formulation might allow this therapy to be used chronically and over larger areas of the body.”

CI is a group of rare genetic keratinization disorders that lead to dry, thickened, and scaling skin. The randomized, parallel, double-blind, vehicle-controlled ASCEND study is designed to enroll 142 participants 6 years of age or older with moderate to severe CI including recessive X-linked ichthyosis (RXLI) and autosomal recessive congenital ichthyosis (ARCI). These subtypes affect about 80,000 people in the U.S. and lead to cutaneous manifestations that include large, dark scaling throughout the body. Timber is providing genetic testing as part of the study for patients whose subtype of CI is not already genetically confirmed. Participants in the ASCEND study are randomized 2:1 to TMB-001 or vehicle control ointment (two participants on TMB-001 for every one participant on vehicle) for 12 weeks, at which point eligible participants in both arms of the study are randomized again to either once-a-day or twice-a-day TMB-001 treatment for an additional 12 weeks to provide valuable information on longer term treatment with the compound.

https://www.biospace.com/article/releases/timber-pharmaceuticals-announces-first-patients-enrolled-in-phase-3-ascend-clinical-trial-evaluating-tmb-001-in-congenital-ichthyosis/

Novartis Tops Busy Week with Solid Tumor Combo Drug Approval

 Switzerland-based Novartis has had a very busy week, and it's not over yet. In addition to patent cases, partnerships and pledging money to global tropical disease efforts, the company scored a win on a combo-treatment for solid tumors.

FDA Greenlights Two-Drug Combo for BRAF V600E Solid Tumors

The U.S. Food and Drug Administration granted accelerated approval to Novartis’ Tafinlar (dabrafenib) plus Mekinist (trametinib) for treatment of adults and children six years and older with unresectable or metastatic solid tumors with a BRAF V600E mutation who have progressed after previous treatment and who have no satisfactory alternative treatment options.

Because it is an accelerated approval, the company has to run confirmatory trials, or the approval could be rescinded. The combo is the first and only BRAF/MEK inhibitor approved with a tumor-agnostic indication for solid tumors with the BRAF V600E mutation. These mutations are associated with 20 different tumor types. 

“The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” Dr. Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas said. “Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors.”

Novartis Pledges $250 Million to Fight Tropical Diseases and Malaria

The company endorsed the Kigali Declaration on neglected tropical diseases (NTDs) and pledged a five-year financial commitment of $250 million to fight NTDs and malaria with the Kigali Summit on Malaria and NTDs. This is along with the 26th Commonwealth Heads of Government (CHOGM) meeting. Novartis initially endorsed the London Declaration on NTDs in 2012, donating to global efforts to eliminate leprosy. The company committed $100 million in 2018 to fight malaria. The new investment will help to advance research and development of new therapeutics against NTDs and malaria. This includes $100 million to focus on four diseases, Chagas disease, visceral leishmaniasis, dengue fever and Cryptosporidium infection.

“Over the past decade, great progress has been made against NTDs, but there is still a lot more work to be done,” Vas Narasimhan, chief executive officer of Novartis, said. “Novartis will continue progressing our longstanding commitment to helping realize a world free of NTDs. Today, by endorsing the Kigali Declaration and pledging to invest $250 million, we aim to accelerate progress toward elimination of these diseases, which continue to cause suffering and stigma for millions of people around the globe.”

Last week, Novartis announced it was collaborating with PerkinElmer to expand newborn screening for sickle cell disease in sub-Saharan Africa. PerkinElmer and the Novartis Africa Sickle Cell Disease program will expand advocacy efforts to educate patients, caregivers and communities on how vital newborn screening and early intervention is with hydroxyurea (HU) and other SCD treatments.

Novartis and Precision Unite on Sickle Cell and Thalassemia Gene Therapies

Novartis and Precision BioSciences inked a partnership to develop a potential cure for hemoglobinopathies, including sickle cell disease and beta-thalassemia. Precision will create a custom ARCUS nuclease and conduct in vitro studies, then Novartis will take over the rest of the R&D, manufacturing and commercialization. Novartis will pay Precision $75 million upfront, but the deal includes up to $1.4 billion in potential milestones, additional research funding and tiered royalties on commercial products.

Jay Bradner, president of the Novartis Institutes for Biomedical Research (NIBR), said, “We identify here a collaborative opportunity to imagine a unique therapeutic option for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia — a potential one-time treatment administered directly to the patient that would overcome many of the hurdles present today with other therapeutic technologies.”

Novartis Loses MS Drug Patent Battle as Appeals Court Reverses Decision 

Yesterday, a U.S. Court of Appeals reversed its own 2020 ruling between Novartis and China’s HEC Pharm. The dispute was over Novartis’ multiple sclerosis drug Gilenya. 

The appeal focused on a specific no-loading-dose limitation in Novartis’ patent description of the drug, which the judges found to be in error. The court ruled in favor of Novartis in 2020, upholding the patient’s drug dosage regimen that prevented HEC and other generic drug companies from challenging the patent until Dec. 25, 2027. HEC filed an Abbreviated New Drug Application with the FDA with plans to produce a generic version of Gilenya before the patent expires in 2027. But the repeal cited experts claiming discrepancies in defining and interpreting the loading dose. Novartis expects to file a petition for further review of the dissolution.

 “Novartis intends to vigorously defend the validity of the patent and is considering all available options, including current plans to seek review of this decision by the full CAFC [U.S. Court of Appeals for the Federal Circuit], a process which may take several months,” Novartis stated.

https://www.biospace.com/article/novartis-tops-very-busy-week-with-solid-tumor-combo-drug-approval/