Britain first to approve Roche's subcutaneous Tecentriq

 The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has become the first regulator to approve Roche's subcutaneous (SC) formulation of cancer immunotherapy Tecentriq, which aims to make treatment easier for patients.

The approval covers all indications for the current intravenous (IV) version of Tecentriq across lung, bladder, breast, and liver cancers, and Roche confirmed this morning that the new version will be provided by the NHS in England.

"We couldn’t have achieved this without the collaboration and support of stakeholders across the cancer community and we remain committed to ensure this treatment is available in Scotland, Wales and Northern Ireland as quickly as possible," said Marius Scholtz, medical director of Roche Products Limited.

Dosing with the SC version takes around seven minutes, while the current IV form requires a 30- to 60-minute infusion, so transitioning to the new form should save time for patients and healthcare staff and conserve resources in healthcare systems, according to Roche.

The MHRA approval covers England, Scotland, and Wales, while at the moment registration in Northern Ireland comes under the remit of the EMA, which has yet to make a decision on the new product. SC Tecentriq is currently under review in the EU, as well as in the US and other countries worldwide.

Last year, Tecentriq became the first SC drug in the PD-1/PD-L1 inhibitor class to clear a multinational phase 3 trial, matching the original formulation in the head-to-head IMscin001 study that involved immunotherapy-naïve patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had previously been treated with platinum-based chemotherapy.

The results showed comparable levels of Tecentriq in the blood when administered subcutaneously, and a safety and efficacy profile consistent with the IV formulation.

So far, approved PD-1/PD-L1 inhibitors headed by MSD's Keytruda (pembrolizumab) and Bristol-Myers Squibb's Opdivo (nivolumab) are all given by IV – other than a product brought to market within China only – so have fought for market share based on their clinical indications.

Now, Roche can add ease of administration to the competitive profile of Tecentriq, and extend the commercial lifespan of the drug with further patent protection. The company said that, while the IMscin001 trial was conducted within hospital settings, SC Tecentriq may be suitable for out-of-hospital administration as well.

Its rivals are not sitting still, however, with MSD and BMS both working on SC versions of their drugs in late-stage trials and Pfizer testing an experimental SC antibody, called sasanlimab, in the phase 3 CREST trial in bladder cancer, with results due next year.

Roche's new drug has been developed using Halozyme's Enhanze drug delivery technology, which has already been deployed in the big pharma's Herceptin (trastuzumab), Rituxan (rituximab), and Phesgo (pertuzumab/trastuzumab) product lines and is being used to create a new version of multiple sclerosis therapy Ocrevus (ocrelizumab).

https://pharmaphorum.com/news/gb-first-approve-roches-subcutaneous-tecentriq

Novartis hits back at Entresto selection on Medicare list

 Novartis has responded to the inclusion of its heart failure blockbuster Entresto on the list of the first 10 drugs that will be subject to Medicare pricing negotiations, claiming that the move will result in "worse access for patients".

The inclusion of Entresto (valsartan/sacubitril) on the list was something of a surprise, as there was no indication it might be under consideration in the build-up to the list's publication yesterday, and Novartis currently isn't among those drugmakers that have filed legal challenges to the negotiation process.

In a statement, the Swiss group said that it believes the negotiation initiative included in the Inflation Reduction Act (IRA) is effectively price-setting by the federal government and unconstitutional, and will "limit the pharmaceutical industry's ability to discover and develop new life-saving and meaningful medicines for the people who need them most."

In particular, it said it will "disincentivise innovation and post-approval research, particularly for small molecule medicines including, among others, those that treat cancer, heart disease, and mental illness – diseases that affect millions of Americans."

According to Novartis, Entresto is the first and only angiotensin receptor-neprilysin inhibitor (ARNi) currently FDA-approved for use in the US for the treatment of heart failure and has no therapeutic alternative, with around 587,000 Medicare patients taking the drug every year.

The company pointed out that, since being approved in 2015 for heart failure with reduced ejection fraction (HFrEF), it has run additional studies to extend the uses of the drug in heart failure, as well as paediatric populations.

"Under the IRA, which discourages the research and development of additional indications for small molecule medicines by implementing price controls nine years after the first FDA approval, we may not have been able to invest in researching and developing Entresto in these additional indications, depriving patients of a meaningful treatment advance," it said.

Former FDA Commissioner Scott Gottlieb – who has been a vocal critic of the IRA's approach to drug negotiations – said he was surprised at the inclusion of Entresto, as well as some others on the list, including AstraZeneca's Farxiga (dapagliflozin), Amgen's Enbrel (etanercept), and Johnson & Johnson's Stelara (ustekinumab).

Calling the policy a "synthetic loss of exclusivity" on drugs, Gottlieb warned of unintended consequences, including a shift towards the development of biologics that now have longer patent terms, reduced incentives for generics drugmakers to challenge patents on small molecule drugs, and a shift of investment out of Medicare indications.

https://pharmaphorum.com/news/novartis-hits-back-entresto-selection-medicare-list

Genentech Alecensa: 'Unprecedented' Phase III Results in Early-Stage Lung Cancer

 

• ALINA data demonstrate Alecensa reduces disease recurrence in the early setting for people with ALK-positive non-small cell lung cancer (NSCLC), building on its long-established benefit in the advanced setting
• About half of people with NSCLC experience disease recurrence following surgery, despite adjuvant chemotherapy, therefore new treatments are urgently needed to provide the best chance for cure
• These data will be submitted to health authorities globally and presented at an upcoming medical meeting

https://www.biospace.com/article/releases/genentech-s-alecensa-delivers-unprecedented-phase-iii-results-for-people-with-alk-positive-early-stage-lung-cancer/

Alvotech Tries Again for FDA Interchangeable Designation for Humira Biosimilar

 Alvotech has resubmitted its Biologics License Application to the FDA seeking an interchangeability designation for AVT02, its high-concentration biosimilar formulation of AbbVie’s Humira (adalimumab), CEO Robert Wessman announced in an investor call Thursday.

Wessman did not disclose a target action date yet but said that Alvotech is working toward a “satisfactory inspection” of its manufacturing campus in Reykjavik, Iceland. If approved, the biotech company also expects AVT02 to be a “material contributor” to its business in 2024.

The FDA has already rejected AVT02 twice. The first was in April 2023, with the regulator citing deficiencies at the Iceland facility in its Complete Response Letter. The second rejection came in June, when the FDA turned down Alvotech’s bid for an interchangeability designation for AVT02.

In July, Alvotech broadened its collaboration with development partner Teva Pharmaceuticals, which involved the latter’s “increased involvement” in manufacturing and quality control at the Reykjavik plant.

Alvotech’s plant was slapped with a warning letter from the FDA in March 2022, which revealed several quality control issues. These included “an unacceptably high number of mold recoveries” from drug manufacturing rooms. The FDA also documented bacterial contamination exceeding acceptable levels.

In addition, the company’s corrective and preventive measures were deemed “inadequate” by the regulator as they did not ensure that future contaminations could be avoided.

“We have made and continue to make significant investments in our manufacturing and quality processes and have taken the feedback received from FDA inspections to focus these investments,” Wessman said during Thursday’s call. “We are confident that the changes that we have made at our site to put the company in the best positions for our satisfactory reinspection.”

If approved, AVT02 will face off with at least eight Humira biosimilars, a group led by Amgen’s Amjevita, which hit the U.S. market in January 2023. The floodgates opened in July, with several other biosimilars launching including Celltrion’s Yuflyma, Organon’s and Samsung Bioepis’ Hadlima, Sandoz’s Hyrimoz and Boehringer Ingelheim’s Cyltezo.

Of these, only Cyltezo has the interchangeability designation, which allows pharmacies to dispense it in place of its branded counterpart without needing a change in prescription.

Alvotech on Thursday also reported its financial results for the first half of 2023 posting $22.7 million in earnings, a substantial increase from its $3.9 million revenue over the same period last year.

https://www.biospace.com/article/alvotech-tries-again-for-interchangeability-designation-for-humira-biosimilar/

BioNTech, DualityBio Move ADC into Phase III for HER2-Low Breast Cancer

BioNTech’s licensed antibody-drug conjugate is moving on to Phase III testing in a potential effort to challenge AstraZeneca and Daiichi Sankyo’s blockbuster Enherto in a heavily treated breast cancer subpopulation. DualityBio, BioNTech’s partner and the ADC’s creator, posted the trial plans Wednesday. 

BioNTech added the ADC, DB-1303, to its portfolio in April 2023 when it paid China’s DualityBio $170 million upfront for rights to it plus a second preclinical asset. Another $1.5 billion is on the line in milestone payments, plus tiered royalties. 

DB-1303 will be pitted against chemotherapy in the open-label Phase III for patients with HER2-low, HR+ metastatic breast cancer patients whose disease has progressed despite endocrine therapy.  

ADC therapy is like a targeted missile for cancer, with an antibody targeted to deliver the cancer killing payload. DB-1303 is a topoisomerase-1 inhibitor. Phase I/II trial results showed the treatment to be well tolerated with encouraging antitumor activity in the already heavily pretreated patient population. 

If approved, BioNTech and DualityBio’s drug could be a strong competitor for AstraZeneca and Daiichi Sankyo’s HER2-directed antibody and topoisomerase inhibitor conjugate. Enhertu has already reached blockbuster status and is projected by to reach annual sales of $2.4 billion for the fiscal year ending March 2024. 

The ADC market continues to be hot. BioNTech’s pandemic partner Pfizer closed the biggest M&A deal of the year with its $43 billion buy of Seagen and its four already-approved cancer ADCs in March 2023. 

In August, BioNTech and DualityBio added another ADC to their collaboration to include a Trop2 antibody-drug conjugate. The third-generation ADC has demonstrated efficacy in non-small cell lung cancer (NSCLC) and other solid tumors. The deals grant BioNTech rights to market the three drugs globally except in mainland China, Hong Kong and Macau, where DualityBio retains commercial rights. 

Gilead’s Trodelvy is currently the only Trop-2 directed ADC approved by the FDA across multiple indications. Sales of the drug, primarily driven by breast cancer, were up to $260 million for the second quarter of 2023, with analysts projecting sales of $2.8 billion by 2028. 

BioNTech has been looking for new revenue streams, returning to its initial focus of cancer therapeutics in the face of sharp COVID-related product sales declines. Revenue for the first half of 2023 fell to $1.5 billion, compared to $10.4 billion during the same time period last year. 

DB-1303 is slated for primary completion of its Phase III by August 2025. 

https://www.biospace.com/article/biontech-dualitybio-move-adc-into-phase-iii-for-her2-low-breast-cancer-/

EU regulator recommends pregnant women not use epilepsy drug topiramate

 The European Medicines Agency's safety committee, on Friday, recommended pregnant women not use topiramate-containing medicines to prevent migraine or manage their body weight as their newborns could have a higher risk of neurodevelopmental disorders.

Topiramate‑containing medicines are currently used in the EU to treat epilepsy and prevent migraines, and in some EU countries, the medicine is also used in combination with phentermine to reduce weight.

The recommendations by the Pharmacovigilance Risk Assessment Committee (PRAC), including one that said women should avoid becoming pregnant while taking the drug, follow a review of three recent observational studies.

Two of those suggested that children born to women who took topiramate-containing medicines while pregnant may have a two- to three-fold higher risk of neurodevelopmental disorders than children born to women with epilepsy, but not taking antiepileptic medication.

These disorders include autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder (ADHD).

PRAC recommends that those using topiramate to treat epilepsy avoid doing so during pregnancy unless there is no other suitable treatment available.

https://news.yahoo.com/emas-safety-committee-warns-pregnant-114201003.html

Centogene shares climb after study confirms biomarker for Gaucher disease

 Shares of Centogene NV (CNTG) gained 7% premarket on Friday after the company announced data confirming the utility of its proprietary biomarker lyso-Gb1 in indicating the severity of Gaucher disease, a rare inherited disorder that affects the body's ability to break down a certain type of fat. The study results also indicate that lyso-Gb1 could help predict the clinical course of patients and personalize care for the disease, Centogene said in a release. "The progressive increase in lyso-Gb1 levels in untreated Gaucher patients suggests that these patients could benefit from treatment, such as enzyme replacement therapy," Dr. Tobias Bottcher, Centogene's director of clinical neurogenetics, said in a statement. Centogene shares have gained 28% in the year to date, while the S&P 500 has gained 17.4%.

https://www.morningstar.com/news/marketwatch/20230901357/centogene-shares-climb-after-study-confirms-biomarker-for-gaucher-disease