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Eli Lilly‘s Olumiant (baricitinib) received approval Monday from the U.S. Food and Drug Administration for the treatment of severe alopecia areata, making it the first systemic treatment for adults living with the disease. 

The approval is based on positive results from the Phase III BRAVE-AA1 and BRAVE-AA2 trials, which involved 1,200 adult patients with severe alopecia areata. After a 36-week observation period, at least 80% scalp hair coverage was achieved in 17% to 22% of the patients who received 2 mg of Olumiant and in 32% to 35% who received 4 mg. These results are significant as those who took a placebo experienced only 3% to 5% scalp hair coverage.  

In addition, 11% to 13% of patients who took 2 mg per day and 24% to 26% of those who took 4 mg per day experienced at least 90% hair coverage, versus just 1% to 4% of patients who were given a placebo. In terms of eyebrow and eyelash coverage improvements, patients given the 4 mg dose saw significant changes at week 36. Most treatment-emergent adverse events were mild or moderate, including headaches, high cholesterol levels, acne, fatigue, nausea, elevated liver enzyme levels and more. 

Severe alopecia areata is characterized by a more than 50% scalp hair loss based on the Severity of Alopecia Tool (SALT). The disease garnered significant media attention recently when Will Smith slapped Chris Rock at the 2022 Academy Awards after the latter made a joke about Smith’s wife, actress Jada Pinkett-Smith, who suffers from alopecia.  

Olumiant is available in 1 mg, 2 mg and 4 mg tablets, with the recommended adult dose being 2 mg per day, to increase to 4 mg if necessary. Patients who have nearly complete or total scalp hair loss, with or without eyebrow hair or eyelash loss, typically start therapy at 4 mg. Once patients respond positively to 4 mg, the dosage is decreased to 2 mg. 

“People with alopecia areata, dermatologists and other healthcare providers have been looking forward to this day when there is an FDA-approved systemic medicine for this often-devastating disease. Alopecia areata causes unpredictable hair loss that can be patchy or complete, and it affects people of all ages and ethnicities,” Brett King, M.D., Ph.D., F.A.A.D., lead investigator of the BRAVE-AA study said. 

Lilly is making Olumiant accessible to many and is working with insurers to make it more affordable. Eligible patients can get help with out-of-pocket expenses through the Oluminant Together support program, which offers a savings card that enables users to pay as low as $5 per month with their insurance or $25 per month if their policy does not cover it. These savings cards are available at specialty pharmacies and for download via the Olumiant.com website. 

“The approval of Olumiant can spark hope for many patients and encourage new treatment conversations with their doctors. The National Alopecia Areata Foundation wants more choices for our patient community and with the approval of Olumiant, there are now new treatment expectations being established in alopecia areata care,” Nicole Friedland, president and CEO of NAAF said. 

Wilmington, Delaware, United States: According to the report, the global regulatory affairs outsourcing market was valued at US$ 4.5 Bn in 2020 and is projected to expand at a CAGR of 19.0% from 2021 to 2028. Regulatory affairs outsourcing refers to the hiring of third-party services by government bodies and private organizations to ensure public health and safety. The services include managing regulatory requirements for generic drugs, innovator drugs, biologics, biosimilars, etc.

Almost a month ahead of schedule, the U.S. Food and Drug Administrationhas approved Alnylam Pharmaceuticals’ Amvuttra (vutrisiran) for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy in adults.

This early decision came as a surprise for many, as the FDA had originally extended the review period from April to July 14.

The disease is rare, inherited, quickly progressive and fatal, with few treatment options. Polyneuropathy is a malfunction of many peripheral nerves throughout the body, and hATTR is caused by mutations in the TTR gene. The TTR protein is mostly produced in the liver and normally carries vitamin A.

The approval was based on positive nine-month data from the Phase III HELIOS-A trial. In it, Amvuttra improved the signs and symptoms of polyneuropathy. More than 50% of patients receiving the drug had their symptoms stopped or reversed.

Alnylam evaluated the efficacy of the drug by comparing the Amvuttra group in HELIOS-A with the placebo group from the Phase III APOLLO trial of patisiran. This was a randomized, controlled trial in a comparable patient population. Patisiran, under the brand name Onpattro, is Alnylam’s approved drug for polyneuropathy of hATTR.

“Twenty years ago, Alnylam was founded with the bold vision for RNA interference to make a meaningful impact on the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs, such as hATTR amyloidosis,” Yvonne Greenstreet, CEO of Alnylam, said in a statement. “Today, Amvuttra has the potential to change the standard of care for people living with the polyneuropathy of this devastating disease.”

The drug is an RNA interference (RNAi) therapeutic. It is made up of a double-stranded small interfering RNA (siRNA) that targets mutant and wild-type transthyretin (TTR) messenger RNA (mRNA). Essentially, it suppresses the expression of a specific gene or gene segment, preventing the production of an abnormal protein. Vutrisiran for polyneuropathy is dosed via subcutaneous injection once every three months.

On Thursday, Alnylam reported that another of its RNAi drugs, cemdisiran, was ready to enter Phase III trials after announcing positive Phase II study results. The drug was co-developed with Regeneron Pharmaceuticals and is designed to treat patients with immunoglobulin A nephropathy (IgAN).

In the Phase II trial, there were 31 patients divided 2:1, placebo to cemdisiran. The patients receiving cemdisiran reported an average 37% decrease in urine protein to creatinine ratio, compared to placebo, recorded over a 24-hour period. The primary endpoint was a change from baseline of the 24-hour urine protein to creatinine ratio.

As BioSpace previously reported, the company announced its five-year strategy, “Alnylam P⁵x25,” at the 2022 J.P. Morgan Health Care Conference in January. This includes the development of several investigational drugs, including RNAi products for Alzheimer’s disease, Stargardt disease and gout.

At the time, Greenstreet said the company will serve “at least half a million patients around the world, as well as bring forward more marketed medicines – six plus – and continue to build this rich clinical pipeline.”

The Alzheimer’s product, ALN-APP, will begin a Phase I trial this year with data expected before 2023. The company’s gout therapeutic, ALN-XDH, is also expected to report Phase I data this year. Vutrisiran is being developed for several diseases, including hATTR and Stargardt disease, which is expected to start a Phase III trial later this year.

“The FDA approval of Amvuttra is very encouraging for the hATTR amyloidosis community, who need additional therapies to address the polyneuropathy of this progressive, life-threatening, multisystem disease,” Dr. Michael Polydefkis, M.D., MHS, professor, Johns Hopkins Neurology and HELIOS-A study investigator, said in a statement. “Amvuttra is a new therapeutic option that has demonstrated the potential to halt or reverse polyneuropathy progression in patients with an acceptable safety profile, along with an infrequent, subcutaneous dosing regimen that may also help to improve the disease management experience for patients.”

Bristol-Myers Squibb’s all-cash offer for Turning Point Therapeutics – which values the biotech at $4.1 billion – bolsters its position in precision oncology and gives it a lead asset that could challenge cancer medicines from Roche and Pfizer.

The $76-per-share offer revolves around repotrectinib (TPX-0005), a tyrosine kinase inhibitor (TKI) targeting ROS1 and NTRK in clinical testing for ROS1-positive, advanced non-small-cell lung cancer (NSCLC) as well as other solid tumours.

The drug is currently being developed in collaboration with China’s Zai Lab in the phase 1/2 TRIDENT-1 study, which aims to recruit around 500 patients and is focusing on a raft of solid tumour types with ALK, ROS1, NTRK1, NTRK2 or NTRK3 mutations.

The study has generated its first results in the ROS1-positive NSCLC cohort, with a 79% overall response rate in patients never previously treated with a ROS1-targeting TKI, made up of 6% complete responses and 73% partial responses.

The results have set up a pre-filing meeting with the FDA, according to BMS. It claims repotrectinib has the potential to achieve a longer duration of response than other ROS1 drugs in this setting – i.e. Roche’s already-approved Rozlytrek (entrectinib) and Pfizer’s Xalkori (crizotinib) – and could be on the market before the end of next year.

Rozlytrek was approved by the FDA in 2019 but has just started to gather sales momentum, making around $17 million in the first quarter of this year, an increase of 78% on the first three months of 2021.

Xalkori is billed as an ALK inhibitor and has been approved to treat ROS1-positive NSCLC since 2016, with sales of $22 million in the first quarter, but is also used to treat ALK-mutated NSCLC and lymphoma.

Roche’s drug, meanwhile, is also cleared to treat NTRK gene fusion-positive solid tumours, an indication that sets it in competition with Bayer’s TRK inhibitor Vitrakvi (larotrectinib).

Repotrectinib has picked up three breakthrough designations from the FDA, including most recently for ROS1-positive metastatic NSCLC patients who have been previously treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy.

“With repotrectinib, we have the opportunity to change the standard of care and address a significant unmet medical need for ROS1-positive non-small cell lung cancer patients,” saidSamit Hirawat, BMS’s chief medical officer.

William Blair analysts said the price BMS is paying for Turning Point is high, given that Rozlytrek and Xalkori have made limited sales to date.

It will, however, add to BMS’ earnings potential from 2025 – when the company will start to bear the brunt of patent expiries on key drugs, including $12.8 billion cancer blockbuster Revlimid (lenalidomide), as well as follow-up Pomalyst (pomalidomide) and chemotherapy Abraxane (albumin-bound paclitaxel).

Another research note from SVB Securities predicted that repotrectinib could eventually become a $1.5 billion product, mainly from first-line use, if it can claim FDA approval for a broad label covering any ROS1-positive cancer.

Meanwhile, the Turning Point deal also features additional clinical-stage drug candidates, including solid tumour therapies elzovantinib, a MET/SRC/CSF1R inhibitor, RET inhibitor TPX-0046, and ALK inhibitor TPX-0131.

Powered by its blockbuster checkpoint inhibitor Keytruda, Merck is forecasting the potential of more than 80 new regulatory approvals in oncology through 2028.

Merck showcased its oncology pipeline at the American Society of Clinical Oncology meeting in Chicago. The company presented data from nearly 120 abstracts in more than 25 cancer types. Over the past decade, Merck’s oncology pipeline has exploded, driven by Keytruda, which is predicted to become the world’s top-selling drug after AbbVie’s Humira loses patent protection next year.

At the ASCO presentation, Dean Y. Li, president of Merck Research Laboratories, reminded us that it’s only been a decade since Phase I data for the drug that would become Keytruda was first presented.

“Since that time, we have created a broad portfolio of oncology medicines with indications in 22 tumor types and have helped usher in a new era of cancer treatment – and most importantly, have helped patients all around the world. With our expansive portfolio and pipeline, we are continuing to help transform care for patients with cancer and hope to receive more than 80 approvals through 2028,” Li said in a statement.

The company highlighted more than 20 investigational candidates targeting multiple aspects of cancer cell biology and immune-based pathways across four distinct research areas. For immuno-oncology, Merck pointed to three ongoing Phase III programs assessing favezelimab, an anti-LAG-3 antibody; quavonlimab, an anti-CTLA-4 antibody; and vibostolimab, an anti-TIGIT antibody. Each of these is being assessed in combination with Keytruda. Also in this space, Merck is developing an anti-ILT-4 antibody, an anti-ILT-3 therapy, and a selective IL-2 agonist.

Antibody-drug conjugates are also being explored by Merck. The company has multiple programs in development, including the Phase III zilovertamab vedotin being assessed in tumors that express elevated levels of receptor tyrosine kinase-like orphan receptor 1. Another ADC in development in collaboration with Seagen is ladiratuzumab vedotin, which is designed to target tumors expressing LIV-1, a zinc transporter protein.

The company is also developing cell-based therapies and T-cell and NK cell engagers for the treatment of different forms of cancer. Merck said that in collaboration with Dragonfly Therapeutics and Janux Therapeutics, it is assessing bi- and tri-specific NK and T-cell engagers. The company is also evaluating allogeneic cell therapies through our collaborations with Artiva and A2 Biotherapeutics.

The fourth area of research is molecularly targeted therapeutics. The company noted that Welireg, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor that was approved last year for the treatment of certain von Hippel Lindau-associated tumors, is being studied in multiple settings, including renal cell carcinoma.

Merck is also developing nemtabrutinib, a selective, oral, reversible non-covalent Bruton’s tyrosine kinase inhibitor, and a small molecule KRAS G12C inhibitor for the treatment of hematological cancers and solid tumors, respectively. Through its 2020 collaboration with Seagen, the company is also studying Tukysa, a tyrone kinase inhibitor, for the treatment of HER2-positive cancers.

Outside of oncology, Merck posted new post-hoc data for its antiviral drug Lagervio (molnupiravir) that showed a lower proportion of COVID-19 trial participants who were treated with the medication required an acute care visit. Fewer patients needed respiratory interventions, the company noted.

Lagevrio received Emergency Use Authorization from the FDA at the end of 2021. It was greenlit for the treatment of mild to moderate COVID-19 infections in adults who are at high risk of progression to severe disease. However, due to some efficacy issues, the FDA EUA limited use of the medication to situations where other treatment options for COVID-19 are not available or clinically appropriate,

The data announced this morning from the Phase III Move-Out study, which assessed the medication in non-hospitalized adults with mild to moderate COVID-19, showed that only 7.2% of patients who received the antiviral required an acute care visit. That was in comparison to 10.6% of placebo patients. Additionally, for those who did require hospitalization, Merck noted that trial data showed patients who received Lagevrio required a shorter stay than those in the placebo group, or nine days compared to 12.

“The analyses add to our understanding of the clinical profile of Lagevrio and help to reinforce the importance of Lagevrio as part of the response to the COVID-19 pandemic,” Li said in a statement.

Lagevrio is also being assessed in a Phase III trial as a prophylaxis treatment for COVID-19.

Owners of an iPhone or Apple Watch have a new health feature, an app called Medications, that will help them manage and track their use of medicines.

The new tool works as a component of Apple’s Health app and will let users add drugs or other health products like vitamins and supplements to a personal list – either by scanning a label or finding the product in a directory – and create custom schedules for them.

Users can also use the built-in health records feature on the Health app to download current medications, said Ricky Bloomfield, a former director of mobile strategy at Duke University who joined Apple as clinical and health informatics lead in 2016 in a tweet.

Medications will issue a reminder when it is time to take one, with the user indicating whether they have taken or skipped a dose, and will keep a record of usage. A customised picture and background can be assigned to each medicine to help avoid errors.

In the US, it will also be able to alert users if there are any interactions between drugs they have added to the Health app that could make them less effective or cause unexpected side effects, said Apple. For example, it can warn of possible issues like mixing drugs like metronidazole or cetirizine with alcohol.

Other features include compatibility with Apple’s health data sharing facility, which allows information to be shared securely with healthcare staff or carers, and the ability to export a medications list into a PDF.

New atrial fibrillation feature

Medications was just one of the health-focused updates released as Apple previewed its new iOS 16 and watchOS 9 operation systems at its Worldwide Developers Conference this week. Another was a new feature for the Apple Watch, which has a built-in ECG that can already be used to identify signs of atrial fibrillation (AFib), a potentially serious heart condition.

Now, users who are diagnosed with AFib can turn on an FDA-cleared AFib History feature that provides another layer of information, including an estimate of how frequently a user’s heart rhythm shows signs of AFib.

They will receive weekly notifications to understand frequency and view their AFib history in the Health app, including lifestyle factors that may influence the condition, like sleep, alcohol consumption, and exercise.

A similar documenting approach has been applied to the Sleep app, which is used to maintain healthy sleep habits and track sleep patterns.

The update expands the information available by using the Apple Watch’s accelerometer and heart rate sensor to detect sleep stages – i.e. REM, core and deep sleep – using machine learning techniques.

Astellas has become the latest big pharma company to sink some money into immuno-oncology start-up GO Therapeutics, forging an alliance to develop antibodies targeting two glycoprotein targets.

The Japanese drugmaker is paying $20.5 million upfront to get the ball rolling, while milestone and other payments could take the total value of the deal up to $783.5 million.

Cambridge, Massachusetts-based GO – led by CEO Constantine Theodoropulos – was formed to develop a cancer immunotherapy platform based on targeting O-glycoproteins, a group of molecules that seem to present differently on cancer cells compared to normal cells.

Cancer O-glycoproteins tend to have truncated sugar side chains (O-glycans), which means they can be targeted by therapeutics without causing off-target effects on healthy tissues.

O-glycoproteins with truncated O-glycans are absent from normal tissues but are present in 60-80% of human epithelial cancers, according to the biotech. That’s a very broad category, spanning lung, breast, ovarian, gastric, colon, and pancreatic solid tumours.

The therapeutic approach has already attracted Swiss pharma group Roche, which paid $9 million in start-up fees to GO in 2018, to buy into the approach with another $186 million offer at the back end.

For Astellas, GO will discover high-affinity antibodies against the O-glycoprotein targets, with the Japanese drugmaker responsible for subsequent research activities, clinical development and commercialisation if they reach the market.

The deal comes after Astellas has had a difficult few months in its R&D operations, headlined by safety issues affecting its AT132 gene therapy candidate for rare disease X-linked myotubular myopathy (XLMTM) acquired as part of its $3 billion takeover of Audentes Therapeutics.

AT132 remains on clinical hold following four patient deaths that may be linked to potential liver-related side effects, and Astellas has also terminated the development of three Duchenne muscular dystrophy gene therapy candidates in preclinical development.

Astellas has made immuno-oncology one of its core R&D areas and has several candidates in clinical development headed by ASP7517, a cell therapy for acute myeloid leukaemia and myelodysplastic syndrome that has reached phase 2 testing.

Medical imaging specialist Median Technologies has launched a new business unit that will provide decision-making tools – underpinned by artificial intelligence – for sponsors of clinical trials in oncology.

The new Imaging Lab business will deploy AI, data mining, and radiomics technologies to medical imaging data generated in cancer trials, said Median.

The new unit will draw on Median’s iBiopsy platform – a software as a medical device (SaMD) being developed for a range of diagnostic procedures in oncology, including lung cancer screening and liver cancer diagnosis and recurrence prediction – and its iCRO contract research business unit focusing on image management in clinical trials.

The company said Imaging Lab will provide a toolkit that is increasingly relevant for new cancer therapeutics development as the biopharma industry focuses increasingly on drugs to detect and treat cancers at an earlier stage.

Last month, Median said that it was preparing to file for FDA approval of iBiopsy for lung cancer screening, aiming at a green light for the SaMD before the end of 2023, based on study data showing 94.7% sensitivity and 93.3% specificity in detecting cancer in lung nodules from a cohort of 1,760 patients.

The platform can be used to select patients for inclusion in clinical trials, particularly studies that are aiming to include patients diagnosed with early-stage disease, as well as for predicting response to therapy, measuring disease progression, and evaluating the safety of drug candidates, said Median.

The hope is that the use of iBiopsy in trials will accelerate go/no go decisions, raising the success rate of trials, which is particularly low in oncology, according to the company.

Bringing a new cancer drug to market costs an average of $2.8 billion, it said, compared to $1 billion for new medicines in other therapeutic categories, citing data from a 2020 analysis published in the Journal of the American Medical Association.

“Our experience of image management in clinical trials has shown that trial data is vastly underutilised,” said Nicolas Dano, chief operating officer of Median’s iCRO division.

“We can extract much more information from images through the widescale use of data mining, AI, and radiomics and use these technologies to better support our customers and biopharmaceutical partners in their clinical developments” he added.

Sanofi and Regeneron should hear from the FDA in the autumn whether it will approve their blockbuster immunology drug Dupixent as a therapy for rare skin disease prurigo nodularis (PN).

The US regulator has granted Dupixent (dupilumab) a six-month priority review in PN and is due to deliver a verdict by 30 September, offering patients hope of a first-approved therapy for the highly-debilitating disease.

Additional regulatory filings outside of the US are also planned in 2022, said the partners.

PN causes hard lumps or nodules to form on the skin that are so itchy they can lead patients to scratch themselves to the point of bleeding or pain.

At the moment, treatment typically involves oral or topical corticosteroids, antihistamines and some antidepressant drugs, but responses are often inadequate, vary widely between patients, and come with the burden of safety risks if used long-term.

The review is based on a pair of phase 3 trials of Dupixent in PN patients whose symptoms were inadequately controlled with current drugs.

The PRIME and PRIME2 studies both showed that the IL-4 and IL-13 inhibitor significantly improved disease signs and symptoms compared to placebo, including reduction in itch and skin lesions.

In almost half (45%) of patients, Dupixent treatment resulted in clear or almost clear skin  at 24 weeks, compared to 16% of controls, and patients also report significantly greater improvements in measures of health-related quality of life, skin pain and symptoms of anxiety and depression

Dupixent is already approved to treat atopic dermatitis and other indications including severe asthma, chronic rhinosinusitis with nasal polyposis, and most recently eosinophilic oesophagitis.

The drug has become a powerhouse for revenues at Sanofi and Regeneron, with the company pitching at peak sales of €10 billion ($10.75 billion) a year and some analysts predicting levels could go as high as $12.5 billion.

PN is among a clutch of additional indications driven by type 2 inflammation that could account for upwards of $2 billion of that total, although if approved Dupixent may not have long on the market before it faces competition.

Potential rivals emerging through the industry pipeline include AbbVie’s JAK inhibitor Rinvoq (upadacitinib), Leo Pharma’s IL-13 antibody tralokinumab, Chugai/Galderma’s IL-31-targeting nemolizumab, Trevi Therapeutics’ mu opioid acting Haduvio (nalbuphine ER), and Kiniksa Pharma’s vixarelimab, which also acts via the IL-31 pathway.

GlaxoSmithKline has agreed a $3.3 billion takeover of US biotech Affinivax, buying a pneumococcal vaccine candidate that is aiming to break into a market that for years has been dominated by Pfizer’s Prevnar franchise.

GSK said it is paying $2.1 billion upfront for Cambridge, Massachusetts-based Affinivax, with another $1.2 billion in potential development milestones, to get its hands on the ASP3772 shot, which recently claimed a breakthrough designation from the FDA for the treatment of pneumococcal disease in older adults.

Last year, Affinivax reported positive phase 2 results with ASP3772, which targets 24 of the common serotypes of Streptococcus pneumoniae – a bacteria which causes non-invasive illnesses like pneumonia, sinusitis and middle ear infections, as well as invasive diseases like meningitis.

In February, the company reacquired full rights to the shot from Astellas, which paid $10 million upfront to license the vaccine in 2017, clearing the way for GSK’s acquisition.

GSK is one of the pharma industry’s top vaccine producers, giving Affinivax’ shot the marketing muscle it will need to challenge Pfizer’s Prevnar 13 and Prevnar 20 products – targeting 13 and 20 pneumococcal serotypes respectively – which together brought in around $5.3 billion in sales last year.

The pandemic and the timing of US government purchases for immunisation campaigns trimmed back sales from almost $5.9 billion in the previous year, but revenues bounced back in the first quarter of 2022, rising 59% to $1.57 billion.

That rise came despite the approval of Merck & Co’s 15-valent Vaxneuvance in July 2021, which has posed the first major challenge to the Prevnar family.

With ASP3772, GSK could offer a shot with broader coverage of pneumococcal serotypes than any of its rivals, and which also includes two “conserved” pneumococcal proteins – antigens that seem always to be present in the bacterium regardless of its serotype.

The vaccine is based on Affinivax’ multiple antigen presenting system, or MAPS, which combines polysaccharide and protein antigens joined with a biotin-rhizavidin bond. The biotech says this can stimulate both B cell (antibody) and T cell immune responses with a single shot.

GSK is also acquiring Affinivax’ pipeline, which includes a 30-valent pneumococcal shot in preclinical development as well as candidates for Klebsiella pneumoniae and Pseudomonas aeruginosa – two other respiratory pathogens – plus Staphylococcus aureus and Clostridium difficile.

“The proposed acquisition further strengthens our vaccines R&D pipeline, provides access to a new, potentially disruptive technology, and broadens GSK’s existing scientific footprint in the Boston area,” said GSK’s R&D chief Hal Barron.