Sarclisa regimen reduced risk of disease progression or death by 45% compared to standard of care in patients who had relapsed after one to three prior therapies
While the median progression free survival (PFS) for Sarclisa combination therapy is not yet reached, consistent improvement in PFS is seen across patient subgroups
This is the second FDA approval for Sarclisa in combination with standard of care backbone therapies
BioXcel Therapeutics, Inc. (“BioXcel” or the “Company”) (NASDAQ: BTAI), a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, today announced topline results from its Phase 1b/2 proof-of-concept RELEASE study of BXCL501, the Company’s proprietary, orally dissolving thin film formulation of dexmedetomidine, for the treatment of opioid withdrawal symptoms.
The study met its primary safety endpoint across multiple doses given twice-daily over seven days. BXCL501 was generally well tolerated, with no severe or serious adverse events reported, and dose dependent exposures were observed across all doses evaluated (30 mcg, 60 mcg, 90 mcg, 120 mcg, 180 mcg and 240 mcg).
With respect to retention, a secondary endpoint, the study showed that patients in multiple dose cohorts treated with BXCL501 had numerical improvements in retention rates, a key goal of opioid withdrawal treatment. The 120 mcg and 180 mcg dose groups showed 42% and 52% rates of retention at Day 6 of BXCL501 treatment, respectively, versus 24% for placebo, though observations were not statistically significant. The results also showed that of the 87% of patients who had fentanyl in their systems upon entry, greater than 50% remained fentanyl positive following the morphine stabilization phase of 5 days. Consequently, withdrawal symptoms were not equivalent across various dose cohorts indicating morphine did not normalize withdrawal symptoms. Improvements were not observed in the severity of opiate withdrawal as measured by the Short Opiate Withdrawal Scale of Gossop (“SOWS-Gossop”) or the Clinical Opiate Withdrawal Scale (“COWS”). The Company believes that the high fentanyl prevalence and lack of normalization observed in study subjects could have confounded these results and made them difficult to interpret.
“We’re encouraged that the RELEASE study helped us to identify a dose range that was generally well tolerated and resulted in numerical improvements in retention in this patient population," commented Reina Benabou, M.D., Ph.D., Senior Vice President & Chief Development Officer. "We’ll continue to analyze these results in collaboration with our advisors regarding potential next steps for this important indication.”
https://finance.yahoo.com/news/bioxcel-therapeutics-announces-results-phase-200100981.html
For several years now, Akebia has been chasing rival anemia drug developer Fibrogen, which appeared to be ahead in its development of a similar acting treatment and would-be competitor to vadadustat.
Fibrogen applied for FDA approval last year, only to have a potential December decision delayed until March. Then, at the beginning of the month, the company and its investors were taken by surprise when the agency indicated it would call an advisory committee meeting to review Fibrogen's drug.
At least twice before, Fibrogen claimed, the FDA had indicated it wouldn't convene a panel, making the last-minute communication an unexpected and potentially costly twist. No date has yet been set, and the FDA has now missed its March 20 goal. The company has not issued any update.
Now that Akebia has submitted its application, the FDA may seek to convene an advisory committee meeting covering both drugs, wrote Christopher Raymond, an analyst at Piper Sandler, in a note to clients.
Both drugs are designed to replace current injectable therapies with a more convenient pill option. They are known as HIF-PH inhibitors and work by promoting red blood cell production in a way that mimics the body's response to low-oxygen environments.
Studies have shown both pills can match the efficacy of injectable drugs. But their safety, particularly for the heart, has become a key concern, especially following Akebia's results last year. Those findings could make the approval case for both drugs harder to regulators, given both are meant to be at least as safe, if not safer, than the injectable medicines like Aranesp that are already tied to potential heart problems.
Akebia's submission came one to two months ahead of expectations, and the company indicated it did not include in its filing a priority review voucher. Such vouchers are a kind of a regulatory fast-pass and can be used to shorten FDA review times by four months.
In early 2020, Akebia had struck a deal with partner Vifor Pharma to hold onto a voucher Vifor bought for about $100 million. The agreement specified the companies would either use it on vadadustat or resell it and share the proceeds.
But the delay facing rival Fibrogen, and resulting uncertainty on the FDA's view of HIF-PH blockers, may have weakened the case for seeking a speedier review. Once a rare commodity, vouchers are now more common but can still fetch around $100 million in a sale.
The FDA now has 60 days to determine whether Akebia's application is complete and ready for an official review.
https://www.biopharmadive.com/news/akebia-fda-application-vadadustat-anemia-ckd/597556/
One of the most important decisions in the history of the Food and Drug Administration is quickly approaching. By early June, the agency should have a verdict on whether to approve aducanumab, a potentially first-of-its-kind treatment for Alzheimer's disease that became a major source of hope and controversy over the last two years.
Aducanumab is meant to the slow the cognitive decline that Alzheimer's patients experience by combating what many believe to be the root cause of disease. Such a treatment would be in high demand, given Alzheimer's care has been limited to medications that alleviate symptoms rather than change the disease's course. However, the data supporting aducanumab have come under intense scrutiny, leaving many doctors and researchers on the fence about its seeming benefit.
In November, the FDA convened a group of experts who advise the agency about brain drugs, and asked them whether there was enough positive evidence to say aducanumab works. Their answer was resoundingly negative, with all but one member voting against the drug.
While the FDA typically follows the recommendations of its advisers, it isn't required to. The agency is under immense pressure to clear more Alzheimer's treatments. And with certain high-ranking members of the FDA taking a favorable view of aducanumab, it's possible the drug may still be approved.
Perhaps that's why, on Tuesday, three of those FDA advisers rehashed their arguments against aducanumab in an editorial published in JAMA. The authors were Caleb Alexander, a professor of epidemiology and medicine at Johns Hopkins University; Aaron Kesselheim, a professor of medicine at Harvard Medical School; and Scott Emerson, a professor emeritus of biostatistics at the University of Washington.
The three were among the most vocal committee members in criticizing Biogen's case for aducanumab at the November meeting.
In their editorial, Alexander, Emerson and Kesselheim noted how the two large, near-identical clinical trials meant to prove aducanumab's merit showed very different results. One found patients who received a high dose for a long enough period of time did significantly better on a cognitive test than patients who received placebo. The other had the opposite outcome.
The authors called out the after-the-fact analyses that aducanumab's developer, Biogen, used to explain the disparate results. Namely, they took issue with how these "post hoc" analyses essentially presumed the positive study was reliable and the negative study was more a fluke, even though the consistent failure of drugs that work like aducanumab would suggest otherwise.
"In short, while post hoc analyses are useful for generating interesting hypotheses to be tested in future trials, the post hoc analyses regarding aducanumab provided limited information useful in deciding the benefit of this new drug and these post hoc analyses should not be the basis for FDA approval," they wrote.
The authors also detailed the close working relationship between the FDA and Biogen to analyze the clinical trial data. This "unusual degree of collaboration ... has been criticized as having potentially compromised the FDA's objectivity" in reviewing the drug, according to the three advisers.
While the authors acknowledged the dire need for safe and effective Alzheimer's drugs, and commended Biogen for running two large, valuable clinical trials, they ultimately see "no persuasive evidence to support approval of aducanumab at this time." FDA statisticians, ahead of the November advisory committee meeting, drew similar conclusions.
Though the arguments brought up in the JAMA article aren't new, "the decision by these authors to reiterate these points speaks to the degree to which they strongly believe that an aducanumab [rejection] is the correct decision here," wrote Brian Skorney, an analyst at Baird who's been critical of aducanumab and its approval odds.
The advisory committee members "clearly want FDA to remember what they said and not allow the long time frame between the meeting and the new [review deadline] to diminish their conclusions," Skorney added in his March 30 note to clients.
https://www.biopharmadive.com/news/aducanumab-fda-advisers-jama-alzheimers/597643/
President Emmanuel Macron on Wednesday ordered France into its third national lockdown and said schools would close for three weeks as he sought to push back a third wave of COVID-19 infections that threatens to overwhelm hospitals.
With the death toll nearing 100,000, intensive care units in the hardest-hit regions at breaking point and a slower-than-planned vaccine rollout, Macron was forced to abandon his goal of keeping the country open to protect the economy.
“We will lose control if we do not move now,” the president said in a televised address to the nation.
His announcement means that movement restrictions already in place for more than a week in Paris, and some northern and southern regions, will now apply to the whole country for at least a month, from Saturday.
Departing from his pledge to safeguard education from the pandemic, Macron said schools will close for three weeks after this weekend.
Macron, 43, had sought to avoid a third large-scale lockdown since the start of the year, betting that if he could steer France out of the pandemic without locking the country down again he would give the economy a chance to recover from last year’s slump.
But the former investment banker’s options narrowed as more contagious strains of the coronavirus swept across France and much of Europe.
For school-children after this weekend, learning will be done remotely for a week, after which schools go on a two-week holiday, which for most of the country will be earlier than scheduled.
Thereafter, nursery and primary pupils will return to school while middle and high school pupils continue distance learning for an extra week.
“It is the best solution to slow down the virus,” Macron said, adding that France had succeeded in keeping its schools open for longer during the pandemic than many neighbours.
FASTER VACCINATIONS
Daily new infections in France have doubled since February to average nearly 40,000. The number of COVID-19 patients in intensive care has breached 5,000, exceeding the peak hit during a six-week-long lockdown late last year.
Bed capacity in critical care units will be increased to 10,000, Macron said.
The new lockdown risks slowing the pace of France’s economic recovery from last year’s slump. It will force the temporary closure of 150,000 businesses at a cost of 11 billion euros ($12.89 billion) per month, the finance ministry said
The set-back for France, the euro zone’s second-largest economy, may also dampen Europe’s hopes of bouncing back swiftly from the pandemic, in the way that the U.S. and Chinese economies are doing.
France’s new lockdown underlines the cost of the European Union’s slow rollout of anti-COVID vaccines.
Neighbouring Britain, which finalised its divorce with the bloc on Jan. 1., has inoculated nearly half its population against the coronavirus and is re-opening its economy just as France hunkers down once again.
Macron said the vaccine campaign needed to be accelerated. Mired early on in red tape and slowed by supply shortages, it is only now finding its stride three months in, with just 12% of the population inoculated.
Bringing the calendar forward, Macron said people in their sixties would be eligible for a shot from mid-April and those in their fifties a month later. A goal of 30 million adults inoculated by mid-June remained the target, he said.
Seeking to offer hope, Macron said the April lockdown and a swifter vaccination campaign would allow the slow re-opening of the country from mid-May, starting with museums and the outdoor terraces of bars and restaurants, albeit under strict rules.
“We can see a way out of this crisis,” Macron said.
20.1% Lower Bound of Preliminary ORR Analysis Exceeds Required 8.3% Threshold
Delcath Systems, Inc. (NASDAQ: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, today provided additional information regarding the power calculation for the Phase 3 FOCUS trial of HEPZATO KIT (melphalan hydrochloride for injection/hepatic delivery system) in patients with liver dominant metastatic ocular melanoma (mOM).
In the summer of 2018, the Company amended the protocol for the FOCUS trial to a single arm design. In consultation with FDA, the FOCUS single arm trial was powered to demonstrate a superior Overall Response Rate (ORR) versus checkpoint inhibitors, one of the few mOM treatment categories with a significant amount of peer reviewed publications.
A point estimate of 21.0% ORR was calculated as the requirement to demonstrate superiority over the checkpoint inhibitors given the planned trial size and this threshold was shared with investors. The checkpoint inhibitor ORR was calculated based on a meta-analysis covering 16 different publications and 476 patients. The pooled overall response rate was 5.5% with a 95% Confidence Interval of 3.6% - 8.3%. To achieve statistical significance at a 95% Confidence Interval the lower bound of the ORR for HEPZATO needs to exceed the 8.3% upper bound of the meta-analysis. A preliminary analysis of 87% of enrolled patients analyses by the Independent Review Committee yielded an ORR of 29.2% [95% CI: 20.1, 39.8] in the Intent to Treat population, which substantially exceeds the 21.0%-point-estimate requirement. For further clarity, since the 20.1% lower bound exceeds the 8.3% upper bound of the meta-analysis the predefined success threshold was met. Further detail is available on the events and presentations section of the company website.
https://finance.yahoo.com/news/delcath-systems-inc-shares-additional-185500289.html
TG Therapeutics has completed its rolling FDA filing for its U2 combination therapy consisting of the antibody ublituximab with the oral drug Ukoniq (umbralisib) as a treatment for chronic lymphocytic leukaemia (CLL).
The US pharma is mounting a challenge to Roche, which markets an antibody therapy, Gazyvaro (obinutuzumab) in advanced CLL.
Like Gazyvaro, ublituximab targets a receptor known as CD-20 that is over-expressed on the surface of malignant B-cells that cause the disease, but adds umbralisib, an oral inhibitor of PI3K-delta and CK1-epsilon.
This adds to the potency of the medication by interfering with receptors that play an important role cell proliferation and survival, and regulate protein translation in cancer cells.
TG Therapeutics began a rolling filing with the FDA for the combination in December, following a $275 million fundraiser to bankroll late development and launch after supportive trial findings announced at the American Society of Hematology conference late last year.
The filing includes the UNITY-CLL phase 3 trial, a randomised study comparing the U2 combination therapy with an active control arm in which patients received Roche’s Gazyvaro plus chlorambucil chemotherapy in both treatment-naïve patients and those with relapsed/refractory disease.
The FDA had previously given the combination Fast Track designation, which allowed extra support to hasten development, as well as orphan drug development.
The trial met its primary endpoint of superior progression-free survival (PFS) for the U2 combination compared to the control arm to support the submission of the U2 combination in CLL.
Patients were randomly placed into four treatment arms: ublituximab single agent, UKONIQ single agent, ublituximab plus UKONIQ, and the active control arm.
A prespecified interim analysis was conducted to assess the contribution of ublituximab and UKONIQ in the U2 combination arm and allowed for the termination of the single agent arms.
The trial continued recruitment in a 1:1 ratio into the two combination arms: the investigational arm of U2 and the control arm of obinutuzumab plus chlorambucil.
About 420 subjects enrolled to the two combination arms and approximately 60% of patients were treatment-naïve and 40% were relapsed or refractory.
https://pharmaphorum.com/news/tg-therapeutics-completes-fda-filing-for-roche-challenger-in-cll/
