NHS Grants Fast Track Access to Takeda’s Exkivity

Takeda has secured UK approval for its lung cancer therapy Exkivity, with an NHS access deal that could see it prescribed to patients within the next few weeks.

The Medicines and Healthcare products Regulatory Agency has granted conditional marketing authorisation to Exkivity as monotherapy for non-small-cell lung cancer patients.

At the same time, NHS England, cost-effectiveness watchdog NICE and Takeda have agreed on an early access deal for the drug that includes a discount on its monthly cost of around $25,000.

According to Sajid Javid, Secretary of Health and Social Care, Exkivity will be available to eligible patients in England “on a budget-neutral basis to the NHS while NICE completes its ongoing appraisal”.

It is expected that around 100 people per year in England will be eligible for the treatment with the drug, the first oral therapy specifically designed for people with NSCLC.

Another drug targeting the EGFR exon20 mutationJohnson & Johnson’s Rybrevant (amivantamab) – is under regulatory review by the MHRA and NICE but is administered by intravenous infusion.

“Trials demonstrate that some patients who have taken mobocertinib have lived for approximately two years after being treated with the breakthrough drug, which is significantly longer than expected for patients with this type of lung cancer,” said NHS England.

Exon 20 insertions are seen in approximately 10% of patients who present with EGFR mutations and 2% of NSCLC patients overall.

NHS national medical director Prof Stephen Powis said that patients in England will be the first in Europe to get access to Exkivity – at an affordable price for the taxpayer – “thanks to another deal struck by the NHS.”

Earlier examples include deals for Amgen’s first-in-class KRAS inhibitor Lumykras (sotorasib) for KRAS-mutated non-small cell lung cancer, Novartis’ cholesterol-lowering Leqvio (inclisiran) that can be dosed once every six months, and AstraZeneca’s Tagrisso (osimertinib) for non-small cell lung cancer with EGFR exon 19 or exon 21 mutations.

FDA Clears BMS’s First LAG-3 Checkpoint Inhibitor

Bristol-Myers Squibb has won FDA approval for the first LAG-3 inhibitor drug ahead of its competitors in cancer immunotherapy, including Merck & Co.

The US regulator cleared Bristol-Myers Squibb’s LAG-3 drug relatlimab as a fixed-dose combination with its PD-1 inhibitor Opdivo (nivolumab) – under the brand name, Opdualag – in patients aged 12 or over suffering from unresectable/metastatic melanoma.

The company has brought the antibody to market ahead of Merck’s favezelimab, which is being developed as a combination with PD-1 inhibitor Keytruda and started a phase III clinical trial in colorectal cancer last year.

Like PD-1, LAG-3 is a negative regulator of T-cells, suppressing their activity against cancer cells, so when that brake is released, the immune system can attack and kill tumors.

The FDA approved Opdualag on the strength of the phase 2/3 RELATIVITY-047 trial in unresectable/metastatic melanoma, which demonstrated that patients on the combination drug had a median progression-free survival of 10.1 months, versus 4.6 months for Opdivo alone.

Safety-wise, no new signals or types of clinically essential events were identified with the fixed-dose combination therapy compared with Opdivo monotherapy.

However, there were more grade 3/4 drug-related adverse events, coming in at 18.9% in the combination arm compared to 9.7% with Opdivo, and discontinuation rates were 14.6% and 6.7%, respectively.

The results nevertheless make Opdualag an alternative to Opdivo plus Yervoy (ipilimumab) – BMS’ notoriously hard to tolerate CTLA4 checkpoint inhibitor – which has been approved as a monotherapy for melanoma since 2011 and as dual therapy with Opdivo since 2015.

In trials, more than 50% of melanoma patients treated with Yervoy had grade 3/4 side effects, although the top-line efficacy of the Opdivo/Yervoy combination looks a little better than Opdualag.

Despite its safety issues, Yervoy is a $2 billion product for BMS, so there is a risk that relatlimab could start to cannibalize some of those revenues. However, the CTLA4 inhibitor is approved alongside Opdivo for several other cancers.

That includes renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC) and mesothelioma. It’s worth noting also that Yervoy is not too far away from patent expiry, so Opdualag will help bolster BMS’ cancer immunotherapy franchise once biosimilar rivals reach the market.

BMS has high expectations for Opdualag, saying previously it expects sales to reach $4 billion before the end of the decade. Still, it remains to be seen how the combination fares in other tumor types, with trials on the go in lung and colorectal cancers.

The company told Reuters it expects the drug will cost $27,389 per infusion after discounts. That is roughly in the same ballpark as the Opdivo/Yervoy combination for melanoma.

FDA Approves Bristol Myers’ Opdivo combo Opdualag for Melanoma

Bristol-Myers Squibb has established the third cancer checkpoint inhibitor class, returning to its immuno-oncology roots in melanoma with an FDA approval. The new drug, relatlimab, a LAG-3 antibody, has been approved in a fixed-dose combination with BMS’ PD-1 inhibitor Opdivo for the treatment of unresectable or metastatic Melanoma. The product will be marketed under the brand name Opdualag. With this approval, BMS now has three checkpoint inhibitors on the market, including its CTLA-4 blocker Yervoy. All three drugs were approved for the first time in Melanoma, as was the duo immunotherapy cocktail Opdivo and Yervoy.

Opdualag was approved based on data demonstrating that it can double the amount of time patients with previously untreated advanced Melanoma can live without disease progression when compared to Opdivo alone. Patients on the fixed-dose combo had a median progression-free survival of 10.1 months in Phase 3 RELATIVITY-047 trial, compared to 4.6 months for Opdivo alone.

According to BMS, approximately one-third of advanced melanoma patients are currently treated with PD-1 monotherapy, including Merck & Co.’s Keytruda. A third are receiving Opdivo-plus-Yervoy, while the remaining third, primarily those with BRAF mutations, are receiving targeted therapies such as Novartis’ Tafinlar and Mekinist.

The relatlimab-Opdivo combination is an important component of BMS’ plan to overcome the patent protection losses of three of its top-selling drugs—blood cancer therapy Revlimid, Pfizer-shared blood thinner Eliquis, and Opdivo—within a decade. According to the company, the new partnership could generate more than USD 4 billion in sales by 2029.

Biogen Publishes Phase 3 Aduhelm Data

Biogen has disclosed the results of its Phase 3 clinical trials for Alzheimer’s drug Aduhelm in a peer-reviewed journal, allowing clinicians to analyse the data and assess its efficacy and safety after months of discussion over its validity.

On the other hand, the choice of the journal appears to be adding to the controversy surrounding the troubled drug, which has only been used to treat a few patients since the FDA granted its accelerated approval last June.

The paper on the results of Phase 3 ENGAGE and EMERGE trials was published in the Journal of Prevention of Alzheimer’s Disease (JPAD), a fairly well-established journal with less prestige than one might expect for featuring the first drug claimed to be disease-modifying in Alzheimer’s.

EMERGE, as previously reported, demonstrated a statistically significant change across primary and secondary clinical endpoints, including the Clinical Dementia Rating Sum of Boxes (CDR-SB) at week 78, whereas ENGAGE failed across the board.

The FDA eventually approved Aduhelm based on the reduction in amyloid-beta plaques observed in patients treated with the drug, a surrogate marker associated with cognitive effects that Biogen associates with the drug.

Vitaris Wins FDA Approval for First Generic of AstraZeneca’s Symbicort

Viatris announce the FDA approval for the first generic of AstraZeneca’s Symbicort (budesonide and formoterol fumarate dihydrate) Inhalation Aerosol, Breyna™ to treat Asthma and Chronic Obstructive Pulmonary Disease (COPD). Breyna is a drug-device combination product consisting of a metered-dose inhaler, developed by Viatris in collaboration with 3M spin-off company Kindeva Drug Delivery. The drug is not to be used to treat acute asthma attacks, the FDA said. Symbicort generated $2.7 billion in revenue from global sales for AstraZeneca last year, while the sales were nearly around $1 billion from the US healthcare market.

Breyna is being approved for asthma in patients six years of age and older; and the maintenance treatment of airflow obstruction and reducing exacerbations for patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

In 2018, AstraZeneca sued Viatris’ Mylan Pharmaceuticals for alleged infringement. In March 2021, a district court ruled in favour of AstraZeneca. Later back in December 2021, the U.S. Court of Appeals for the Federal Circuit changed the infringement decision and transmitted the case back down to the lower court for more proceedings. Viatris is looking forward to launching Breyna in 2022, subject to the upcoming court proceedings development.

Currently, the drug treatments for asthma in the market include long-term control treatments, such as inhaled corticosteroids, long-acting beta-agonists, and oral medications. The approval of Breyna provides high hope for many patients living with these two common pulmonary health conditions. As per the WHO, globally, Asthma affects nearly 260 million people and caused around 461000 deaths in 2019. In the United States, approximately 25 million people are affected with asthma, which is equal to about 1 in 13 Americans and includes 8 per cent of adults and 7 per cent of children (which is more than five million). Similarly, according to DelveInsight’s estimates, COPD has a higher diagnosed prevalence in the United States with 17,455,600+ diagnosed cases of COPD in 2020, which is expected to increase in the coming years. 

Moderna Seeks FDA Approval for Second COVID-19 Booster Shot

In one of the latest updates in the COVID-19 vaccine development, the Biotechnology giant Moderna has requested the FDA to grant emergency authorisation for a second booster shot of its COVID-19 vaccine covering all adults over 18 who’ve received approved vaccines. It is an mRNA vaccine that can provide higher immune protection. Moderna is seeking approval for the booster shot based on the recent data from Israel and the US, following the emergence of the omicron variant. Moderna’s first booster shot was authorised for emergency use in November 2021. Currently, Moderna’s first booster is administered after a month of its two doses of primary vaccines.

Earlier, the other major players in the COVID-19 therapeutics segment, Pfizer and its partner BioNTech also requested authorisation for a second booster shot. However, the overall coverage of the population is smaller as it will be available for people aged 65 & older and who’ve been vaccinated. Additionally, both Moderna and Pfizer are also evaluating omicron-specific booster shots, the data for which is expected to release in the coming days.

Currently, countries like Israel have started administering the fourth dose to adults. The booster shots applications by pharma and biotech companies have raised several questions regarding how long vaccines are capable to protect from infection. Will people require to take repeated shots to generate infection-fighting antibodies and prevent severe disease and death? 

FDA Approves Marinus’ Ztalmy for CDKL-5 Deficiency Disorder

The recent FDA approval of Ztalmy (ganaxolone) developed by Marinus Pharmaceuticals, comes as the first and only FDA-approved treatment therapy for seizures associated with CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) – a rare form of genetic epilepsy, in patients of two years of age and older. An oral suspension, the first FDA approved treatment for this specific CDD, is considered to be a neuroactive steroid that serves as a positive allosteric modulator of the GABAA receptor. 

CDD is a very rare as well as serious genetic disorder that can be characterized by early‑onset and difficult‑to‑control seizures. The cause of this disorder is mutation of the cyclin-dependent kinase-like 5 (CDKL5) gene, situated on the X chromosome. The CDKL5 gene generates a protein necessary for normal brain function and development. The approval from the US regulatory was done on the basis of results from a Phase 3 Marigold, double-blind, placebo-controlled trial, where 101 participants who went under the study, were randomized and individually treated with ZTALMY. The participants indicated that Ztalmy significantly reduced major motor seizure frequency in CDD patients in the pivotal Marigold trial.

Some of the common side effects that were observed through the study included somnolence, fever, salivary hypersecretion, and seasonal allergy. ZTALMY is anticipated to be launched and commercially available in the U.S. from July following the schedule by the U.S. Drug Enforcement Administration. 

Merck’s Keytruda + Lynparza Combo Trial Fails for Prostate Cancer

Merck & Co’s and AstraZeneca’s two blockbuster oncology drugs namely Keytruda and Lynparza have both given disappointing results and failed to show efficacy when delivered to patients in combination with previously treated metastatic castration-resistant prostate cancer (mCRPC). The results were taken from the KEYLYNK-010 trial, which included a combination of PD-1 inhibitor Keytruda (pembrolizumab) with AstraZeneca-partnered PARP inhibitor Lynparza (olaparib) in prostate cancer men whose cancer progressed after chemotherapy and anti-androgen therapy.

The study was done to compare Keytruda/Lynparza treatment to that of anti-androgen therapy with either Pfizer/Astellas Xtandi (enzalutamide) or Johnson & Johnson’s Zytiga (abiraterone), but eventually was found with no improvements, whether in  interim analyses on radiographic progression-free survival (rPFS) or for overall survival (OS).

The study outcomes are considered to be a rare setback for both Keytruda and Lynparza, as they are already seen as extremely efficacious drugs in their respective classes. Lynparza is approved as a second-line treatment for homologous recombination repair (HRR) gene-mutated mCRPC, whereas Keytruda is struggling to make an impact in prostate cancer treatment. This disease is nowhere to be seen in the long list of approved indications for Keytruda.
On the other hand, Merck and AZ are still running clinical trials for better outcomes of the drug combinations in treatment of other cancer forms such as lung cancer, ovarian cancer and triple-negative breast cancer (TNBC).