España: MSD sube en bolsa...adquisiciones y aprobaciones.

 

La compañía biomédica MSD, conocida como Merck en Estados Unidos, ha registrado un gran primer semestre de 2024 en términos bursátiles a nivel global, especialmente durante el inicio del año. Prueba de ello es su rendimiento en el mayor mercado de valores del mundo, la Bolsa de Nueva York, influenciado principalmente por las adquisiciones llevadas a cabo en este periodo y las numerosas aprobaciones por parte de la Agencia del Medicamento de Estados Unidos (FDA, por sus siglas en inglés).

Tras un aumento del 6,38% en diciembre de 2023, la compañía norteamericana comenzaba el año con un valor de 109,16 dólares (101,85 euros) la acción, que en tan solo un mes subió hasta los 120,78 dólares (112,62 euros) un 10,79% más. Continuando con la tendencia positiva, en febrero la farmacéutica incrementó de nuevo su valor por acción, en esta ocasión un 5,27%, que seguido del aumento del 3,78% dejarían un gran primer trimestre, con 22,79 dólares (21,26 euros) y un 19,84% más.

Tras un sorpresivo aumento del 6,38% en diciembre de 2023, la compañía norteamericana comenzaba el año con un valor de 101,85 euros la acción, que en tan solo un mes subió hasta los 112,62, un 10,79% más Por parte del segundo trimestre no ha sido tan positivo, en abril cayeron a números rojos, después de encadenar cinco meses en positivo. Una inclinación negativa que continuó tanto en mayo como en junio, provocando así que el valor por acción de MSD se situase en los 123,80 dólares (115,51 euros) a cierre de junio.

A pesar de los registros de estos tres últimos meses, el resultado de la compañía en el primer semestre es muy positivo, gracias al buen momento que atravesaron tanto en enero, con esa subida de más del 10%, como en febrero y marzo, que alcanzaron el 8% entre ambos. En términos totales, los seis primeros meses de 2024 de MSD dejan un incremento de 14,64 dólares (13,66 euros), lo que se traduce en un crecimiento del 13,53%.

ADQUISICIONES Y APROBACIONES

Estos seis meses para la compañía norteamericana han estado influenciados principalmente por las adquisiciones que han llevado a cabo, el refuerzo de su compromiso con la sostenibilidad, y las múltiples aprobaciones que han ido recibiendo por parte de la FDA.

En cuanto a las adquisiciones, en los primeros días del año, la empresa global de productos farmacéuticos anunció un acuerdo con el laboratorio Harpoon Therapeutics por un total de 680 millones de dólares (634,47 millones de euros) con el objetivo de diversificar su cartera de tratamientos oncológicos. Una operación que, tal y como apuntó el presidente de Merck Research Laboratories, Dean Y. Li, supone un gran paso para MSD, “las adquisiciones estratégicas complementan nuestra cartera actual y promueven avances científicos revolucionarios para ayudar a abordar las necesidades de las personas con cáncer en todo el mundo", añadió.

Continuando con las adquisiciones, a finales de mayo, la compañía estadounidense comunico la compra de Eyebiotech Limited (EyeBio), una empresa privada de biotecnología centrada en la oftalmología. En este caso, la cifra monetaria se situó en los 3.000 millones de dólares (2.799 millones de euros), incluido un pago inicial de 1.300 millones de dólares (1.202 millones de euros) y otros 1.700 millones de dólares (1.586 millones de euros) potenciales en pagos por hitos comerciales, regulatorios y de desarrollo.

“Las adquisiciones estratégicas complementan nuestra cartera actual y promueven avances científicos revolucionarios para ayudar a abordar las necesidades de las personas con cáncer en todo el mundo" Por parte de la compañía adquirida, se encuentra en desarrollo de una cartera de candidatos clínicos y preclínicos para la prevención y el tratamiento de la pérdida de visión asociada con la fuga vascular retiniana, un factor de riesgo para las posteriores enfermedades de la retina. "Seguimos ejecutando nuestra estrategia de desarrollo empresarial basada en la ciencia para ampliar y diversificar nuestra cartera. El equipo de EyeBio, bajo el liderazgo del Dr. David Guyer y el Dr. Tony Adamis, tiene una sólida trayectoria en el desarrollo de terapias oftalmológicas innovadoras”, destacó Dean Y. Li.

Además de los acuerdos alcanzados con otras compañías, MSD ha conseguido contabilizar este gran primer semestre en bolsa gracias a las aprobaciones de la FDA, que demuestran que la compañía va por un buen camino. Como por ejemplo el tratamiento de adultos con hipertensión arterial pulmonar (HAP) para mejorar la capacidad de ejercicio y reducir el riesgo de eventos de empeoramiento clínico. Este fármaco biológico innovador, se trata del primer tratamiento innovador ador de la señalización de activina aprobado por la FDA para la HAP.

Otro de los puntos en los que ha puesto en especial el foco MSD en este semestre ha sido la enfermedad neumocócica en adultos, alcanzando la aprobación de la FDA a mediados de junio de su vacuna de próxima generación. Bajo el nombre de Capvaxive, han conseguido producir una respuesta inmune contra los 21 serotipos, o variaciones de la bacteria, a los que se dirigió la inyección en una variedad de poblaciones adultas en los estudios. En esta misma línea, en el día de ayer la compañía comunicó que la FDA también había aprobado su terapia V116 en Estados Unidos y se encuentra en proceso de revisión por la Agencia Europea de Medicamentos (EMA).

Ver

The renaissance of Alzheimer´s drug development

 

With 14 million people in Europe expected to suffer from Alzheimer’s and other forms of dementia by 2030, the race is on to find a treatment to not only slow its course, but even prevent the development of the disease.

Historically, market authorisations for neurological diseases have had significantly lower rates of success compared with other indications.

Between 2000 to 2015, the likelihood of approval for neurological drugs that entered phase 1 trials (8.4%) was below the mean across all indications (9.6%) and far below haematology (26.1%) and infectious diseases (19.1%). When considering neurodegenerative diseases and specifically Alzheimer’s disease (AD), the rate is even lower with only four drugs: donepezil; galantamine; memantine, and rivastigmine approved between 1996 and 2020.

These drugs, however, only treat the disease’s symptoms rather than the causes. This has largely been due to a lack of understanding of the mechanisms behind disease pathogenesis, with advances in AD happening at a significantly slower rate relative to other diseases. Despite being first discovered over 100 years ago, the complexity of the brain and limitations surrounding research/diagnostic methods and models have acted as barriers for AD drug development.

Recently, however, this trend has begun to shift. In 2021, while cancer drugs accounted for 30% of all new FDA approvals, neurology saw the second most approvals for the third time in a row (10%). 

The AD pipeline in particular saw major advancements with the (controversial) FDA accelerated approval of Biogen’s Aduhelm (aducanumab) in 2021, the first amyloid-targeting antibody for AD. The FDA approval of Eisai’s Leqembi (lecanemab) in July 2023 – with Lilly’s donanemab submitted but awaiting a currently delayed advisory committee meeting in 2024 (both of which also target amyloid) – continue to highlight the advancements happening in AD therapeutics.

A closer look at amyloid targeting treatments and beyond

Amyloid plaques, targeted by the aforementioned therapeutics, form from a protein known as amyloid-beta (Aβ), which is produced through the proteolytic cleavage of amyloid precursor protein (APP). The cleavage of APP has two different pathways known as the non-amyloidogenic and the amyloidogenic pathway. The non-amyloidogenic pathway results in soluble APP (sAPP) and a fragment known as P3 being released, with both being cleared from the brain. Alternatively, the amyloidogenic pathway, which is the main interest in AD, results in the generation of oligomeric Aβ40 or Aβ42, which are deposited within the brain and over time, through a process known as aggregation, form insoluble plaques.

.../... 

In the next 12 months, it is also likely there will be the approval of at least one more amyloid drug in Eli Lilly’s donanemab globally. In addition, potential approval of a subcutaneous formulation of Eisai’s Leqembi (currently requesting an FDA Fast Track designation) will offer patients greater accessibility due to not requiring access to a transfusion centre, with data showing increased efficacy and comparable safety to the current intravenous Leqembi.

Beyond 2024, the general consensus among HCPs and key opinion leaders active in the AD clinical space is that combination therapies with existing drugs for AD will start being developed, with therapeutic efficacy further enhanced by doing so. These could manifest in several ways including combining Aβ (Leqembi/donanemab) and TREM2-targeting drugs (AL002) or Aβ and tau (E2814)-targeting combination therapies.

Increased funding and greater public awareness of AD impact on people’s lives will continue to influence future innovation in these areas. The potential financial benefits are also certainly an incentive for drug developers with the Alzheimer’s market estimated to be $4.2bn in 2022 and expected to grow to $15.6bn by 2030. The financial burden on payers and governments has led to the recognition by regulatory bodies of an unmet need and is also contributing to advancements in AD therapeutics. With AD and other dementias responsible for a cost of $2.8trn in 2019 and expected to cost $4.7trn by 2023 globally, the race is truly on.

How the pipeline continues to develop may be dependent on the success of Leqembi, but as the first amyloid drug to be covered for reimbursement, it has paved the way for subsequent developments. While the actual clinical and commercial success of Leqembi is still to be determined, the market remains open, highlighting the requirement for further development.

 

Más...

AZ: FDA autoriza Imfinzi para "endometrial cancer"

 

AstraZeneca’s (AZ) Imfinzi (durvalumab) has been approved by the US Food and Drug Administration (FDA) as part of a combination therapy for a subset of endometrial cancer patients.

Imfinzi plus carboplatin and paclitaxel, followed by Imfinzi monotherapy, is now authorised to treat adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).

The FDA’s decision was supported by positive results from the late-stage DUO-E trial, in which the Imfinzi regimen reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer versus chemotherapy alone.

The safety and tolerability profile of the regimen was generally manageable, well tolerated and broadly consistent with prior clinical trials, AZ said.

Endometrial cancer is the sixth most common cancer in women globally and dMMR disease accounts for up to 30% of all cases.

Patients diagnosed at an early stage of disease have a five-year survival rate of up to 90%, but AZ outlined that there remains a “significant need” for new treatment options for those with advanced disease, where the survival rate falls to less than 20%.

Imfinzi, which already holds approvals in lung cancer, biliary tract cancer and hepatocellular carcinoma, is a human monoclonal antibody designed to block the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Commenting on the latest authorisation for the drug, Dave Fredrickson, executive vice president, oncology business unit, AZ, said: “There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future.

“Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting and the approval of Imfinzi offers an important new option for patients with dMMR disease.”

DUO-E has also been evaluating Imfinzi plus chemotherapy, followed by Imfinzi plus Lynparza (olaparib), as a maintenance therapy. Regulatory applications for both Imfinzi and Imfinzi/Lynparza regimens are currently under review in the EU and several other countries based on results from the study.

Ver

Nuevas fusiones: NOVO, GILEAD, NOVARTIS...

 

Según la consultora, que destaca siete adquisiciones valoradas en más de mil millones, incluida una por encima de los 10 mil millones de dólares (9.240 millones de euros), estos datos auguran un gran año de fusiones y adquisiciones para el sector biofarmacéutico, ya que el total del primer trimestre ha eclipsado los totales inferiores a 10.000 millones de dólares que tuvieron lugar en el primer trimestre de 2020 y 2022, y fue significativamente superior a los más de 22.000 millones de dólares registrados en el primer trimestre de 2021.

El acuerdo más importante del trimestre ha sido el de Novo Holdings, el accionista mayoritario de Novo Nordisk. El grupo se hizo en febrero con Catalent por 16.500 millones de dólares. El objetivo, según se desprende del documento de Evaluate, es mantener su posición líder en el campo de la diabetes tipo 2 y la obesidad gracias al aumento de la producción de semaglutida, un medicamento antidiabético que se usa para el tratamiento de estas enfermedades.

Como parte de la transacción, Novo Nordisk pagará 11.000 millones de dólares para adquirir tres plantas de fabricación de Catalent (dos en Europa y una en EEUU) para aumentar la capacidad de llenado y acabado de productos que contienen semaglutida, como Ozempic, que generó a la farmacéutica 14.000 millones de dólares en ventas durante 2023, y Wegovy, por el cual la empresa danesa ingresó 4.360 millones de dólares.

Apuesta por transacciones más pequeñas El resto de los acuerdos de fusiones y adquisiciones del primer trimestre fueron significativamente más pequeños. Y es que desde 2023, el sector ha dejado atrás las grandes compras y se centra en las pequeñas y medianas empresas debido al mayor escrutinio regulatorio que suele rodear a las grandes operaciones de compraventa en el sector.

El segundo acuerdo más importante del trimestre fue el de Gilead Sciences, que reforzó su apuesta por las enfermedades hepáticas al invertir 4.300 millones de dólares en CymaBay Therapeutics y su agonista PPAR delta de fase III seladelpar para la colangitis biliar primaria. Anunciado el 12 de febrero, el acuerdo se cerró rápidamente el 22 de marzo. CymaBay, con sede en Hayward, California, presentó en diciembre a la Administración de Alimentos y Medicamentos (FDA, por sus siglas en inglés) de EEUU una nueva solicitud de aprobación del fármaco.

El tercer acuerdo más grande en los primeros tres meses de 2024 vino de la mano de Novartis AG, que el pasado 6 de febrero hizo una oferta de 68 dólares por acción por la alemana MorphoSys AG. Una transacción, según Evaluate, valorada en aproximadamente 2.910 millones de dólares y que se espera que se cierre durante la primera mitad de 2024. MorphoSys, que anunció el 22 de marzo que la operación propuesta había superado la revisión de la Comisión Federal de Comercio de Estados Unidos, ha realizado varios estudios de fase III del candidato a mielofibrosis pelabresib y afirma que el inhibidor de BET puede aprobarse, a pesar de algunos resultados dispares en esos ensayos.

Ver

Roche has announced that its blood test, Elecsys pTau217, has been granted breakthrough device designation from the US Food and Drug Administration for earlier diagnosis of Alzheimer’s disease (AD).

The blood test, which is being developed in collaboration with Eli Lilly, works to identify the presence or absence of amyloid pathology in individuals, a pathological feature of the neurodegenerative condition.

AD is a progressive form of dementia that slowly destroys an individual’s memory and thinking skills.

According to the Alzheimer’s Society, around 55 million people are living with dementia globally, which is estimated to rise to 139 million by 2050.

In previous studies, pTau217 has shown the ability to distinguish AD from other neurodegenerative disorders and has demonstrated a strong performance relative to other biomarkers.

To be used in the diagnostic pathway with other clinical information, a positive result of the Elecsys pTau217 test indicates a high likelihood of having a positive amyloid positron emission tomography (PET)/cerebrospinal fluid (CSF) result.

Both companies believe that the plasma biomarker test could play a significant role in improving access to early and accurate AD diagnosis, following approval.

If successful, the test will support healthcare providers in identifying amyloid pathology in individuals and help ensure that they are able to receive the appropriate care, including through participating in clinical trials or by gaining access to approved disease-modifying therapies.

“There is a critical role for diagnostics to play in addressing this global health challenge,” said Matt Sause, chief executive officer of Roche Diagnostics.

“We believe pTau217 is going to be crucial in the diagnosis of AD… [and] we plan to leverage our installed base of diagnostic systems… to ensure we are able to create access to this test for those who need it the most,” Sause added.

Anne White, executive vice president of Eli Lilly and president of Lilly Neuroscience, said: “We’re excited to help meet the growing need for additional diagnostic tools to enable a timely and accurate diagnosis for people with AD.”

Roche announced its partnership with Eli Lilly in March 2023 to develop the blood test for AD to help streamline the journey to diagnosis for more patients.

Ver

CRISPR-Based es ya una realidad terapéutica...

 

The FDA set a target action date of December 8 for a decision on whether to approve Vertex and CRISPR Therapeutics’ CRISPR-Cas9 gene edited therapy for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT), but the UK has beaten it to the punch.

The UK Medicines and Healthcare products Regulatory Agency has conditionally authorized the therapy. “Today is a historic day in science and medicine: this authorization of CASGEVY in Great Britain is the first regulatory authorization of a CRISPR-based therapy in the world,” said Reshma Kewalramani, Chief Executive Officer and President of Vertex, in a statement.

Casgevy (exagamglogene autotemcel [exa-cel]) has been approved for patients aged 12 years and over with “SCD with recurrent vaso-occlusive crises (VOCs) or TDT, for whom a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor is not available.”

In a clinical trial for SCD, 28 out of 29 patients were free of severe pain crises for at least 12 months after treatment. For TDT, 39 out of 42 patients did not need a red blood cell transfusion for at least 12 months following treatment, with the other patients seeing a reduction of more than 70 percent in the need for red cell transfusions. The MHRA says it will monitor the safety of the treatment through real-word safety data and post-authorization safety studies to be conducted by Vertex and CRISPR Therapeutics.

Mas

Fué Ozempic, ahora Zepbound antidiabéticos que bajan de peso...

El último tratamiento aprobado por la agencia regulatoria de fármacos en Estados Unidos, la FDA (Food and Drug Administration), no es nuevo. Al igual que ocurriera con Ozempic, Zepbound es un tratamiento contra la diabetes tipo 2 al que se le ha encontrado un nuevo uso: tratar la obesidad.

Un “nuevo” tratamiento… En los EE UU. 

Y con esa función, la de luchar contra la obesidad, este tratamiento ha sido aprobado para su uso en los Estados Unidos. Zepbound se consolida así como la primera alternativa al fármaco que más ha dado de qué hablar desde el final de la pandemia, la semaglutida. 

 

Zepbound. 

Zepbound es el segundo nombre comercial que se ha dado a la tirzepatida, un compuesto desarrollado por la farmacéutica estadounidense Eli Lilly. Este compuesto también es la base del tratamiento contra la diabetes tipo 2 Mounjaro. 

La FDA ahora ha aprobado el uso de este fármaco como tratamiento contra la obesidad y el sobrepeso.

 

Al igual que la semaglutida se comercializa con dos nombres, Ozempic (contra la diabetes) y Wegovy (para la pérdida de peso), la tirzepatida también estará presente en las farmacias estadounidenses bajo dos marcas, cada una orientada hacia un uso.

Más
 

 

 

 The FDA announced Wednesday that it has approved Eli Lilly's dual GIP and GLP-1 agonist tirzepatide for chronic weight management. Specifically, the weekly injectable medication will be marketed under the name Zepbound for adult patients with obesity, or for those who are overweight and have at least one weight-related condition.

 

"In light of increasing rates of both obesity and overweight in the US, today's approval addresses an unmet medical need," commented John Sharretts, director of the division of diabetes, lipid disorders and obesity in the FDA's Center for Drug Evaluation and Research. Tirzepatide has been cleared in the US as a treatment for diabetes since 2022 under the name Mounjaro. 

The latest FDA decision was based on the Phase III SURMOUNT-1 and SURMOUNT-2 trials. Results from SURMOUNT-1, which included about 2500 participants, demonstrated that at the highest dose of 15mg, patients taking Zepbound lost an average 48 pounds, while at the lowest dose of 5mg, they shed 34 pounds on average. By contrast, participants who received placebo lost 7 pounds (for more, see ViewPoints: ADA 2023 – Tirzepatide study lead investigator says weight loss in type 2 diabetes and ensuing health benefits now a 'SURMOUNT'-able goal). List price of $1060 per month.

 

Eli Lilly said Zepbound should be available in the US by the end of the year in six doses, and carry a list price of about $1060 for a month's supply. Zepbound is the latest entrant into the field of GLP-1 agonists that already includes Novo Nordisk's semaglutide, which is marketed under the names Ozempic for diabetes and Wegovy for weight loss. Eli Lilly said the list price for its drug is about 20% lower than Wegovy. 

Mike Mason, president of Eli Lilly's diabetes and obesity unit, stated that "broader access to [weight loss] medicines is critical, which is why Lilly is committed to working with healthcare, government and industry partners to ensure people who may benefit from Zepbound can access it." 

According to the company, people who are commercially insured with coverage for Zepbound may be eligible to pay as low as $25 for a one-month or three-month prescription. Those who are commercially insured without coverage for Zepbound may be eligible to pay as low as $550 for a one-month prescription. 

 Eli Lilly reported earlier this month that Mounjaro garnered sales of $1.4 billion in the third quarter, up from $187.3 million in the prior year, and surpassing estimates by about $100 million. At the time, Bloomberg Intelligence analysts Sam Fazeli and John Murphy suggested that nothing comes close "to matching Mounjaro's importance to the company's near-term earnings." 

All-time bestseller? 

 Zepbound's approval further establishes Eli Lilly as a formidable competitor to Novo Nordisk in the budding market for weight-loss treatments, with some analysts suggesting it could become one of the best-selling drugs in history. A FirstWord survey from July of 150 US physicians found that nearly all saw an increase in the number of patients seeking treatment for obesity over the past 12 months, although payer resistance had set up a notable barrier to access. FirstWord is working on a new physician's survey, with data to be released in the coming days. 

 Guggenheim analyst Seamus Fernandez said "we think [Zepbound] has a very, very strong shot at being the biggest [selling] drug of all time; obviously competing very closely with Novo Nordisk's Ozempic and Wegovy." 

He noted that the GLP-1 category "for sure, will be the largest selling pharmaceutical market of all time," with the main challenge being reimbursement. "That being said, we do have some really important data coming this weekend from Novo Nordisk's…SELECT study, and that could really prove out…the benefits of [Wegovy] for patients who have high cardiovascular risk, so this may turn out to be more of a cardiovascular drug at the end of the day." 

Más

 

The impact of COVID, flu, and RSV on U.S. and U.K. hospitals is expected to be lower this winter compared to last, as there won't be a significant overlap between peak outbreaks of infections, the London-based data analytics firm Airfinity said in a recent report.

However, with COVID in the mix, the hospital burden is likely to be 3.4 times and 2.6 times higher this season compared to pre-pandemic days in the U.S. and the U.K., respectively.

Airfinity projects hospitalizations linked to the three viruses to peak at 57K weekly admissions at the end of January in the U.S., down from 80K during the last winter.

The COVID wave in the nation is expected to peak in November before flu and RSV spikes early next year, as indicated in the graph below.

Just last week, the CDC warned about a potential "tripledemic" caused by the three respiratory pathogens against which FDA-approved vaccines will be available for the first time this year.

The season's peak outbreaks of COVID, RSV, and flu infections are expected to stretch between September and April, a prolonged duration compared to the rapid but sharp spikes in October and February during the 2022–23 season.

"Uptake of COVID and flu boosters as well as the rollout of the new vaccines to protect older people against RSV, could help reduce this burden further this year," 

Dr. Louise Blair, Airfinity's Senior Director of Analysis and Insights, remarked.

Last week, the CDC endorsed updated COVID-19 boosters from Pfizer /BioNTech  and Moderna. Novavax's updated COVID shot is currently under FDA review.

A few months ago, Pfizer  and GSK  won the CDC nod to roll out their vaccines branded as Abrysvo and Arexvy to prevent RSV infections in people aged 60 years and older.

CSL Limited, GSK , Sanofi  , and AstraZeneca are authorized to market their flu vaccine for the 2023–24 influenza season.

Meanwhile, in the U.K., where a new wave of COVID infections has started, peak weekly hospitalizations are expected to reach 13.5K by late September. Shortly thereafter, flu and RSV waves are set to peak in February and November, respectively, leading to a second peak in hospital admissions.

"We expect this year's peaks to be more in line with historical averages as population immunity is higher and fewer people will be susceptible to severe disease," Airfinity's Dr. Blair added.

Ver

FDA aprueba ZURZUVAE / Biogen en depresión posparto

 

La agencia reguladora del medicamento de Estados Unidos, FDA, acaba de aprobar Zurzuvae (zuranolona, desarrollado por Biogen y Sage). Es el primer medicamento oral indicado para tratar la depresión posparto en adultos.

La depresión posparto es un episodio depresivo grave que suele aparecer tras el parto, pero que también puede comenzar durante las últimas fases del embarazo. Hasta ahora, el tratamiento farmacológico específico se basaba en una inyección intravenosa administrada por un profesional sanitario. 

Con esta aprobación, se abre la posibilidad de la toma del medicamento en el domicilio.

El fármaco es un neuroesteroide que actúa como modulador alostérico positivo del receptor GABA-A. Se incluye dentro de los lanzamientos esperados para este año que destacó la consultora Evaluate por su potencial en ventas.

En un artículos sobre tratamientos disruptivos en psiquiatría publicado en Revista de Psiquiatría y Salud Mental, Eduard Vieta, jefe del Servicio de Psiquiatría y Psicología del Hospital Clínic de Barcelona, ya avanzaba sobre el fármaco que los estudios preliminares indicaban una “excelente tolerabilidad, acción ultrarrápida y dispensación episódica (no requiere tratamiento de mantenimiento) como brexanolona [el medicamento inyectable], y con la ventaja de la formulación oral”.

Esos datos se han corroborado con dos estudios multicéntricos aleatorizados, doble ciego y controlados con placebo.

Más

USA: Stop a Ozempic...

 

It seemed like only a matter of time before someone would close this valve. After months of off-label prescribing of Ozempic, propelled by celebrity hype of the diabetes drug which has gained popularity as a weight-loss treatment, some payers have decided to rein in the practice.

According to a report in The Washington Post last week, some 14 Anthem Blue Cross Blue Shield plans cautioned healthcare providers in several states about prescribing Ozempic to non-diabetic patients. As the “education” letter noted, an inquiry undertaken of those physicians’ claims by the plan’s “Special Investigations Unit” revealed that 60% of patients prescribed Ozempic lacked “sufficient evidence” of diabetes, the product’s Food and Drug Administration-approved use.

Such prescribing could put patients at risk, the insurer warned, threatening the 150 or so prescribers who received the letter that it would refer “suspected inappropriate or fraudulent activity…to the state licensure board, federal and/or state law enforcement.” What’s more, the trend has led to nationwide shortages of the drug for diabetics.

Those warnings portend a future reckoning with regard to new drugs like Ozempic, driven by celebrity and social-media buzz around the medications, which are disrupting the way obesity is treated. The new crop of products, known as GLPs, has proven to be highly safe and effective and is stoking a mad dash by patients to access them and by pharma companies to satisfy the market.

But their high costs – the drugs list for $900 or more per month – put payers in a pickle: should they give the GLPs a warm reception, potentially saving money on downstream medical expenses, or tamp down on what’s shaping up to be a colossal short-term liability?

While carriers are frowning on off-label prescribing now, the spigot could reopen if studies pan out showing that Ozempic and its cousins have cardiovascular and other wider health benefits. Novo Nordisk and Eli Lilly are studying whether use of these drugs decreases comorbidities. 

Más

Alzheimer (aducanumab y lecanemab): fármacos solo para una minoria...

Los pacientes en fases iniciales de la demencia candidatos a las nuevas terapias frente al amiloide serían una pequeña parte del total, según los criterios de los ensayos.

Un nuevo estudio que analiza los criterios de inclusión en los ensayos clínicos de fase III que condujeron a la aprobación por parte la FDA de aducanumab y lecanemab revela que, aplicando estos parámetros, el porcentaje de pacientes en las primeras fases de la enfermedad de Alzheimer y con presencia confirmada de patología beta-amiloide candidatos a las nuevas terapias sería pequeño.

Ambos medicamentos, de Biogen y Eisai, fueron aprobados por la agencia estadounidense por la vía acelerada, que basó su decisión en su efecto reductor sobre el beta amiloide cerebral. Posteriormente, este verano la FDA ha concedido a lecanemab la aprobación tradicional tras constatarse el beneficio clínico del tratamiento en la ralentización de la progresión de la enfermedad. La europea EMA, que ya anunció que solo dará luz verde a fármacos para el alzhéimer con evidencias de eficacia clínica, tiene hasta el 31 de marzo de 2024 para pronunciarse sobre lecanemab.

Este nuevo trabajo, publicado en Neurology, incluyó a una cohorte de 237 personas, de entre 50 y 90 años, con deterioro cognitivo leve o demencia leve y cuyos escáneres cerebrales confirmaron la presencia de patología beta amiloide. Sobre esta muestra, los investigadores quisieron cuantificar el número de pacientes que podrían haber participado en el ensayo pivotal de lecanemab (Clarity-AD) y en los dos estudios de fase III de aducanumab (Engage y Emerge).

Candidatos a lecanemab

En el caso de lecanemab, para entrar en el ensayo clínico los participantes tenían que obtener resultados específicos en ciertas pruebas de pensamiento y memoria, y su índice de masa corporal (IMC) tenía que situarse entre 17 y 35. El 47% de los participantes (112 personas) cumplían estos criterios.

Pero cuando se analizó la presencia de los factores de exclusión en el ensayo, como ictus, enfermedad cardiovascular, antecedentes de cáncer o la detección de anomalías en pruebas de neuroimagen, como hemorragias o pequeñas lesiones cerebrales, solo 19 participantes (8%) se consideraron elegibles para el ensayo con el fármaco.

Sin embargo, tras modificar los criterios de exclusión para incluir a todos los participantes con deterioro cognitivo leve y no aplicar los resultados de las pruebas adicionales de memoria y pensamiento, se halló que el 17% de los pacientes podrían haber sido candidatos a participar en el estudio pivotal.

El caso de aducanumab

Para participar en los dos ensayos pivotales de aducanumab los participantes tenían que tener entre 50 y 80 años y también obtener ciertas puntuaciones en los test de pensamiento y memoria. Con solo estos criterios, 104 personas (44%) podrían haber entrado en los estudios.

Tras eliminar a los que presentaban comorbilidades como accidente accidente cerebrovascular, enfermedad cardiovascular, hipertensión arterial no controlada, antecedentes de cáncer o presencia de anomalías en pruebas de neuroimagen, solo 12 participantes (5%) podrían haber entrado en los estudios con este biológico.

Los criterios de inclusión y exclusión en los ensayos clínicos son determinantes para establecer las condiciones de aprobación regulatoria y el uso de un medicamento una vez llega al mercado. "Nuestro estudio estima que solo un pequeño porcentaje de personas mayores con deterioro cognitivo temprano debido a la enfermedad de Alzheimer pueden ser elegibles para recibir tratamiento con anticuerpos monoclonales frente al beta-amiloide en el cerebro", señala la investigadora Maria Vassilaki, de la Clínica Mayo en Rochester, y miembro de la Academia Americana de Neurología.

Según Vassilaki, los ensayos con estos fármacos adolecen además de una subrepresentación de personas negras e hispanas, pese a que son poblaciones más vulnerables al alzhéimer y otras demencias. "Se necesita investigación adicional para examinar la seguridad y la eficacia de los anticuerpos monoclonales dirigidos a las placas de beta-amiloide en poblaciones más grandes y diversas, así como en poblaciones menos sanas, antes de que estas terapias puedan estar disponibles para las personas con enfermedad de Alzheimer", señala.

"No es café para todos"

Con motivo de la aprobación definitiva de lecanemab por parte de la FDA, la neuróloga Mercè Boada, cofundadora y directora médica del Ace Alzheimer Center Barcelona, ya explicaba a este medio que este tratamiento "no es café para todos".

En este sentido, la experta señalaba la experiencia en el reclutamiento del ensayo Clarity AD que evidencia que el fármaco se dirige grupo seleccionado de pacientes con confirmación de la presencia significativa de amiloide en el cerebro.

Así, de los 5.967 pacientes en fases iniciales de deterioro cognitivo y demencia que inicialmente entraron en el estudio, 4.172 no cumplían los criterios de inclusión en cuanto a niveles elevados de amiloide cerebral o decidieron finalmente no participar porque consideraron el protocolo del estudio demasiado engorroso, lo que sitúa la tasa de fallo de reclutamiento en cerca del 70%.

En el caso del Ace Alzheimer Center Barcelona, este porcentaje se situó en el 64%. "Nosotros empezamos con 42 pacientes, que es un 20% de la población que se incluyó en España, y randomizamos 27". Tras los abandonos por diversos motivos, 17 seguían en la fase de extensión abierta a mediados de julio. 

Naiara Brocal. Diario Médico 17.8.2023 

OZEMPIC lifestile drug...?

It seemed like only a matter of time before someone would close this valve. 

After months of off-label prescribing of Ozempic, propelled by celebrity hype of the diabetes drug which has gained popularity as a weight-loss treatment, some payers have decided to rein in the practice.

Ver: 

Todo sobre Ozempic en PHARMACOSERIAS

According to a report in The Washington Post last week, some 14 Anthem Blue Cross Blue Shield plans cautioned healthcare providers in several states about prescribing Ozempic to non-diabetic patients. As the “education” letter noted, an inquiry undertaken of those physicians’ claims by the plan’s “Special Investigations Unit” revealed that 60% of patients prescribed Ozempic lacked “sufficient evidence” of diabetes, the product’s Food and Drug Administration-approved use.

Such prescribing could put patients at risk, the insurer warned, threatening the 150 or so prescribers who received the letter that it would refer “suspected inappropriate or fraudulent activity…to the state licensure board, federal and/or state law enforcement.” What’s more, the trend has led to nationwide shortages of the drug for diabetics.

Those warnings portend a future reckoning with regard to new drugs like Ozempic, driven by celebrity and social-media buzz around the medications, which are disrupting the way obesity is treated. The new crop of products, known as GLPs, has proven to be highly safe and effective and is stoking a mad dash by patients to access them and by pharma companies to satisfy the market.

But their high costs – the drugs list for $900 or more per month – put payers in a pickle: should they give the GLPs a warm reception, potentially saving money on downstream medical expenses, or tamp down on what’s shaping up to be a colossal short-term liability?

While carriers are frowning on off-label prescribing now, the spigot could reopen if studies pan out showing that Ozempic and its cousins have cardiovascular and other wider health benefits. Novo Nordisk and Eli Lilly are studying whether use of these drugs decreases comorbidities.

Novo sells semaglutide, the active compound in Ozempic, as another drug approved for obesity, Wegovy. The reason doctors are writing Ozempic ‘scripts for treating obesity is because most health plan benefit designs don’t cover weight loss medications.

David Allen, a spokesperson for America’s Health Insurance Plans, says the trade group has concerns about the cost of GLP-1s and side effects, which can include vomiting and nausea, as well as the likelihood of gaining the weight back when the drugs are discontinued. “The evidence is still evolving related to how these medications may impact complications related to obesity such as heart disease and diabetes,” he said.

The fanfare around GLPs has earned them comparisons to Botox and Viagra – products that became cultural phenomena in their own right. But it may be just as appropriate to liken them to Sovaldi, the $1100-per-pill hepatitis C drug which may have been the first to intensify concerns about society’s ability to pay for a high-priced, mass-market pharmaceutical.

Employers are often the ones making these coverage decisions, not insurers themselves. And fewer than a quarter of employer-sponsored plans cover any drug specifically for losing weight, a study by the International Federation of Employee Benefit Plans showed. Even if they do, many of these plans are trying to restrict access to the drugs and alternatives like Lilly’s Mounjaro (tirzepatide), which has also seen an up-tick in off-label prescribing, according to the WaPo.

Not only must patients meet the specifications on the drug’s label – having a body-mass index of at least 30, or 27 if the patient also has a weight-related health condition such as high blood pressure. In order to get Wegovy approval, some employers also look for enrollment in a weight-loss program or taking other weight-loss drugs first.

Nevertheless, the percentage of companies that cover at least a portion of members’ prescription weight-loss medications is expected to rise. Willis Towers Watson’s 2022 Best Practices Survey, for instance, showed that 35% of employers were targeting obesity and weight management as an important clinical area for their employees. And the typical employer’s drug spending could increase by more than 50% if half of employees who were eligible for Wegovy were to take it, according to a WTW estimate.

Thus far, Novo Nordisk enjoys pole position in the weight-loss market with Wegovy. The company saw a 124% year-on-year increase in the sale of obesity medications during first-quarter 2023. The firm reported the equivalent of $3.5 billion in revenue for Ozempic and Wegovy combined in the first quarter, whereas Lilly collected $568.5 million in first-quarter Mounjaro sales.

Competition is coming, though. Later this year, the FDA is expected to approve Lilly’s tirzepatide for obese adults. Pfizer, Amgen and smaller players like Altimmune are among the other companies that are working on weight-loss therapies similar to Wegovy. According to analysts and pharma companies, the market for GLPs or similar treatments is expected to reach $100 billion by decade’s end.

Total prescriptions for Ozempic and Wegovy have risen by 95% and 514%, respectively, versus a year ago, according to a research note from JPMorgan analysts. Payers are taking a cautious approach for now, but analysts predict that access will continue to expand as payers increasingly view obesity as a driver of medical comorbidities that contribute to rising health care costs.

Más

10 Most Promising Drug Launches in 2023 (II)

 

Ver anterior: 

10 Most Promising Drug Launches in 2023 (I)