Small World

“Small molecule therapies will be with us for the foreseeable future, and will almost certainly continue to be used as first-line therapies for the next 10 years,” said Navin Molecular CCO Jordi Robinson, as part of our 10-year anniversary feature “The Multifaceted Future of Pharma”. Amongst the highly sophisticated and ever-evolving pipelines of biopharmaceuticals and cell and gene therapies, the stalwarts of pharmaceutical products – the small molecule medicines – remain. Let’s take a brief look at what’s been making the headlines lately in the small molecule world...

Settle down, Schizophrenia
 

The FDA has approved Bristol Myers Squibb’s schizophrenia treatment Cobenfy (xanomeline and trospium chloride) – the first approval of an antipsychotic with a novel mode of action in more than 50 years. Cobenfy’s approach to schizophrenia treatment is through the selective targeting of the M1 and M4 (muscarinic acetylcholine) brain receptors, which it manages without blocking the D2 (dopamine) receptors. BMS CEO Chris Boerner said, “Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community, where after more than 30 years, there is now an entirely new pharmacological approach for schizophrenia — one that has the potential to change the treatment paradigm. As we reenter the field of neuropsychiatry, we are dedicated to changing the conversation around serious mental illness, beginning with today’s approval in schizophrenia.”

Generics against HIV
 

Gilead Sciences Ireland UC has entered a voluntary licensing agreement with six global pharmaceutical companies (Dr. Reddy’s Laboratories, Emcure, Eva Pharma, Ferozsons Laboratories, Hetero, and Mylan) for the manufacture and commercialization of HIV-1 drug lenacapavir, which is also under investigation for the prevention of HIV (PrEP). With no known cross resistance exhibited in vitro to other existing drug classes, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle, whereas other antivirals act on a single stage of viral replication. Gilead has prioritized registration in the 18 countries that carry the bulk of the HIV burden, with more than 100 more countries included once generic versions become available. CEO Daniel O’Day said, “Given the transformative potential of lenacapavir for prevention, our focus is on making it available as quickly and broadly as possible where the need is greatest. Gilead teams have been working with urgency to bring on high-volume generic manufacturers now, so that we can ensure a rapid transition to these voluntary license partners after lenacapavir for PrEP is approved.”

Innovative allergy treatment
 

Another FDA approval saw ARS Pharmaceutical’s neffy (epinephrine nasal spray) given the green light as a needle-free intranasal treatment for adults and children weighing at least 30 kg (66lbs) with type 1 allergic reactions, including anaphylaxis. Renaissance Lakewood will act in the capacity of CDMO partner. In describing how neffy “changes the paradigm” for allergy sufferers, ARS CEO and co-founder Richard Lowenthal said, “Years of dedication from the entire allergy community and healthcare providers have paved the way for neffy as the first needle-free epinephrine treatment for severe allergies … Now that people can begin using neffy, we are looking forward to seeing how it positively impacts up to 40 million people in the U.S. who experience severe allergic reactions.”

Cutting it against cancer
 

AstraZeneca’s small but mighty non-small cell lung cancer treatment Tagrisso (osimertinib) received FDA approval after showing progression free survival compared to placebo in the phase III LAURA trial. Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said, “The results of the LAURA trial show the powerful impact Tagrisso can make as backbone therapy in this disease, and with this approval, patients across all stages of EGFR-mutated non-small cell lung cancer can now benefit.”

Elsewhere in cancer treatment, Bayer has submitted a supplemental new drug application for darolutamide, developed jointly alongside Finland-based API developer Orion, following further positive results from the phase III ARANOTE trial, in which darolutamide plus androgen deprivation therapy significantly reduced the risk of progression or death by 46 percent compared to placebo in prostate cancer patients. Darolutamide’s distinct chemical structure inhibits receptor function and growth of prostate cancer cells by binding to the androgen receptor and exhibiting strong antagonistic activity. Orion CEO Liisa Hurme said, “This is a historic achievement for Orion and yet another proof of the high-quality research and development work we have been doing for years. With the current track record the future of darolutamide looks bright.”

Kis of life
 

In an updated analysis from a pivotal phase III trial, Novartis’ Kisqali (ribociclib) has shown benefits for early breast cancer patients beyond the three-year treatment period when used in combination with endocrine therapy, reducing the risk of recurrence by 28.5 percent. Novartis CMO Shreeram Aradhye said: “As we anticipate regulatory action from health authorities worldwide, we are highly encouraged by these longer-term results … A large number of people diagnosed with HR+/HER2- early breast cancer remain at risk of recurrence, and these results add to the growing body of evidence supporting the potential of Kisqali to reduce this risk consistently across a broad population.”

But it’s sadly not all good news
 

Pfizer’s sickle cell treatment voxelotor (Oxbryta) has been withdrawn from all markets following an unanticipated number of deaths. Post-marketing clinical trials revealed a higher rate of vaso-occlusive crisis in patients. In a warning notice issued on 26 September, the FDA stated that “Pfizer has determined the benefit of Oxbryta does not outweigh the risk.” On the same date, the EMA also warned that “overall, these data raise serious concerns about the safety of Oxbryta”.

Pfizer CMO Aida Habtezion said, “Our primary concern is for patients who suffer from SCD, which remains a very serious and difficult-to-treat disease with limited treatment options. We advise patients to contact their physicians to discuss alternative treatment while we continue to investigate the findings from our review of the data.”