Carpal Tunnel Syndrome

Met primary and Hepatic Encephalopathy (HE) endpoints in Phase 2 study Increase in Skeletal Muscle Index (SMI) observed at Week 24 was maintained through 52 weeks Participants on placebo increased SMI when switched to LPCN 1148 Fewer Overt Hepatic Encephalopathy (OHE) events and time to first recurrent OHE event was longer while on LPCN 1148 therapy LPCN 1148 was well-tolerated, with AE rates and severities similar to placebo. Participants on LPCN 1148 were hospitalized for fewer days SALT LAKE CITY, March 28, 2024 /PRNewswire/ -- Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company today announced positive topline results from a Phase 2 clinical study of LPCN 1148. LPCN 1148 is an oral candidate under development for the clinical management of cirrhosis, specifically prevention of OHE recurrence and treatment of sarcopenia. LPCN 1148 is targeted to be a "First in Class" product candidate with a novel mechanism of action (MOA). Lipocine plans to meet with the FDA to discuss a development path to NDA filing. "We are encouraged with the positive results from our Phase 2 study. These results demonstrate that LPCN 1148 treatment benefits patients with cirrhosis who are sarcopenic and have experienced other serious decompensation events such as OHE," said Dr. Mahesh Patel, President and CEO of Lipocine Inc. "Cirrhosis management is a significant unmet medical need with a strong pharmaco-economic rationale. We believe LPCN 1148 both ameliorates sarcopenia and decreases the recurrence of OHE. If approved, this treatment is a compelling opportunity with the potential to be the standard of care as a mono or adjunct therapy in managing advanced cirrhosis." This Phase 2 proof of concept study was a randomized placebo-controlled study in sarcopenic male patients with cirrhosis on the liver transplant waitlist. In Stage 1, 29 patients were randomized 1:1 to receive either LPCN 1148 or matching placebo for 24 weeks. At Week 24, the open-label extension Stage 2 of the study commenced. During Stage 2, 8 participants who were on placebo in Stage 1 converted to LPCN 1148, and 11 participants who started the study on LPCN 1148 continued treatment with LPCN 1148. The study's primary endpoint was a change in L3-SMI at week 24. L3-SMI estimates whole body skeletal muscle mass. SMI was analyzed at baseline, and Weeks 12, 24, 36, and 52. Key secondary endpoints included rates of hepatic encephalopathy and the safety/tolerability of LPCN 1148. Results All LPCN 1148-treated participants completed Week 24 (n=15), and 10 of 14 placebo participants completed Week 24. During the initial 24 weeks, all LPCN 1148-treated participants had at least one evaluable post-baseline CT scan and are therefore part of the modified intent to treat (mITT) analysis; 10 placebo-treated participants had an evaluable post-baseline CT. As prespecified, L3-SMI analysis was performed on the mITT population (n=25), with the last evaluable post-baseline observation carried forward (LOCF). Of those participants on placebo in Stage 1, 6 out of 8 who went on to receive LPCN 1148 starting at Week 24 had evaluable CT scans in Stage 2. Primary endpoint Participants who received LPCN 1148 during Stage 1 had a significant (p<0.01) increase in L3-SMI of 4.1 cm2/m2 (8.8%) at Week 24, the primary analysis timepoint, and this increase was maintained through the additional 28 weeks of the study (Week 52, 4.1 cm2/m2, 8.7%). Placebo participants who began receiving LPCN 1148 saw a marked increase in SMI as early as 12 weeks after therapy initiation (Week 36, 7.4 cm2/m2, 15.1%), and this increase was maintained through Week 52 (8.1 cm2/m2, 16.7%). Table 1: Change in L3-SMI at Week 24 and Week 52 Data are least squares mean (standard error), LOCF. # For Placebo participants converted to LPCN 1148, baseline is considered Week 24 data. ANCOVA model with treatment and overall baseline L3-SMI as covariates. * p<0.01 vs baseline. † p<0.01 LPCN 1148 vs placebo at Week 24. ‡ Change from baseline in SMI at Week 24 was the study's primary endpoint. Hepatic Encephalopathy Recurrent OHE is defined as an event of OHE in a participant with a medical history of HE. Most (22/29, 76%) study participants had experienced HE prior to this study, and there were similar numbers of these participants in each study arm in both Stage 1 and Stage 2. Nearly all (21/22, 95%) participants with a history of HE were on therapy for HE at baseline and during the study (lactulose and/or rifaximin). During Stage 1, LPCN 1148 treatment resulted in significantly (p<0.05) fewer cases of recurrent OHE (1 vs 6), a potential FDA-approvable endpoint. During the open-label Stage 2, there were two cases of OHE, one in a participant who was receiving LPCN 1148 since Day 1, and one who began receiving LPCN 1148 at Week 24. The average time to first OHE recurrence was longer with LPCN 1148 treatment, at 183 days compared to 35 days for placebo. Safety set; includes all participants who received study drug in a given stage. Overt HE (OHE) is defined as an event of HE with CTCAE severity ≥ grade 2. Safety In this 52-week study, LPCN 1148 was well-tolerated with AE rates and severities similar to those observed in Stage 1 with placebo. Participants experienced fewer serious or severe adverse events when switched from placebo to LPCN 1148. Participants on LPCN 1148 were hospitalized for fewer total days with shorter hospital stays. There were two deaths reported in placebo-treated participants and one in LPCN 1148-treated participants during the study. The company plans to share additional results pertaining to other secondary endpoints at upcoming scientific conferences. Dr. Arun J. Sanyal, MD, Director, Stravitz-Sanyal Institute for Liver Disease & Metabolic Health, Virginia Commonwealth University, commented, "I am delighted to see the durability of the results noted in this important trial to improve sarcopenia in a very sick population of patients with decompensated cirrhosis. The stability of improvement in sarcopenia and encephalopathy provide proof of concept that sarcopenia correction with LPCN 1148 may provide benefit to patients with decompensated cirrhosis and reduce the risk of breakthrough encephalopathy. These provide a strong rationale for further studies on the overall benefits and risks of LPCN 1148 in this population where there is a major unmet need to improve sarcopenia." Dr. Jennifer Lai, MD, MBA, UCSF Professor of Medicine, transplant hepatologist, and study principal investigator, added, "The rapid and sustained increases in muscle mass seen in this study with LPCN 1148 are very exciting, especially as there are currently no FDA-approved pharmacotherapeutics for sarcopenia in cirrhosis. The observed trends towards improved clinical outcomes including hepatic encephalopathy support what we know about the importance of increasing and maintaining muscle mass in patients with cirrhosis." About Cirrhosis Cirrhosis is an end stage liver disease of varying etiologies such as alcoholic liver disease, chronic viral hepatitis, nonalcoholic fatty liver disease and primary cholangitis. Complications of cirrhosis include decompensation events such as hepatic encephalopathy due to systemic ammonia buildup, variceal bleeding, and ascites, which require frequent hospitalizations. In addition, many patients exhibit sarcopenia (low muscle mass). Over 382,000 patients have been diagnosed with decompensated liver cirrhosis in the US, with few options for managing their disease other than liver transplant. Poor quality of life is common while waiting for a liver transplant. Although there is a limited supply of donor livers, transplant is the only cure for end-stage cirrhosis. About HE HE is a frequent complication and one of the most debilitating manifestations of liver disease, severely affecting the lives of patients and their caregivers. For patients with decompensated liver cirrhosis and sarcopenia, clinical outcomes tend to be worse - both sarcopenia and myosteatosis are associated with an increased risk of HE. OHE is an episodic neurological disorder with a high recurrence rate. Up to 50% of patients with cirrhosis will experience an OHE episode in their lifetime. Patients can exhibit global neurological, psychiatric, and musculoskeletal deficits. HE has a complex pathophysiology that includes impairment of ammonia clearance and increased inflammatory cytokine and HE recurrence is common, despite use of standard-of-care therapies. Options for prevention/treatment are limited, resulting in significant enduring unmet medical need as the 1-year survival for patients with OHE is ~50%. Furthermore, cognitive impairment associated with cirrhosis results in utilization of more health care resources. About LPCN 1148 LPCN 1148 comprises testosterone dodecanoate, a unique androgen receptor agonist. It is targeted as a differentiated intervention option with a novel multimodal MOA to elicit potential benefits in management of cirrhosis and associated comorbidities of cirrhosis. About the Phase 2 study This multi-center study enrolled and dosed a total of 29 patients across 8 centers in the United States. The primary objective was to evaluate the efficacy of 24 weeks of LPCN 1148 treatment in men with cirrhosis and sarcopenia. The secondary objective was to evaluate the safety and tolerability of LPCN 1148. Following Week 24, the open-label stage of the study began (Stage 2), wherein all participants received LPCN 1148 (no placebo in Stage 2). Baseline characteristics, including age, disease etiology baseline L3-SMI, and other comorbidities were generally well-balanced between groups. Overall, the average baseline Model for End-Stage Liver Disease (MELD) score was 16.8, and 97% of patients had previously experienced at least one clinical decompensation event. Sarcopenia, or low muscle mass, was assessed by computed tomography (CT) scan; total skeletal muscle area at the third lumbar vertebra was measured by CT scan and normalized by participant height (L3-SMI, L3-skeletal muscle index). Patients had study visits every four weeks, with CTs performed at Weeks 12, 24, 36, and 52. Patients with a variety of cirrhosis etiologies were eligible. During the study there were no restrictions on standard of care medications, procedures, or other interventions. Further details on the study design, including inclusion and exclusion criteria, can be found on Clinicaltrials.gov (NCT04874350). About Lipocine Lipocine is a biopharmaceutical company leveraging its proprietary technology platform to augment therapeutics through effective oral delivery to develop products for CNS disorders. Lipocine has drug candidates in development as well as drug candidates for which we are exploring partnering. Our drug candidates represent enablement of differentiated, patient friendly oral delivery options for favorable benefit to risk pro target large addressable markets with significant unmet medical needs. Lipocine's clinical development candidates include: LPCN 1154, oral brexanolone, for the potential treatment of postpartum depression, LPCN 2101 for the potential treatment of epilepsy and LPCN 1148, an oral prodrug of bioidentical testosterone targeted for the management of symptoms associated with liver cirrhosis. Lipocine is exploring partnering opportunities for LPCN 1107, our candidate for prevention of preterm birth, LPCN 1148, for the management of decompensated cirrhosis, and LPCN 1144, our candidate for treatment of non-cirrhotic NASH. TLANDO, a novel oral prodrug of testosterone containing testosterone undecanoate developed by Lipocine, is approved by the FDA for conditions associated with a deficiency of endogenous testosterone, also known as hypogonadism, in adult males. For more information, please visit . Forward-Looking Statements This release contains "forward-looking statements" that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and include statements that are not historical facts regarding our product development efforts, our product candidates and related clinical trials, our strategic plans for developing products to treat CNS disorders, our ability to monetize non-core product candidates, including through entering into partnering arrangements, the application of our proprietary platform in developing new treatments for CNS disorders, the timing and completion of regulatory reviews, outcomes of clinical trials of our product candidates, the potential uses and benefits of our product candidates, the potential uses and benefits of LPCN 1148, and the timing of and our ability to make any NDA filing relating to LPCN 1148. Investors are cautioned that all such forward-looking statements involve risks and uncertainties, including, without limitation, the risks that we may not be successful in developing product candidates to treat CNS disorders, we may not be able to enter into partnerships or other strategic relationships to monetize our non-core assets, the FDA will not approve any of our products, risks related to our products, expected product benefits not being realized, clinical and regulatory expectations and plans not being realized, new regulatory developments and requirements, risks related to the FDA approval process including the receipt of regulatory approvals and our ability to utilize a streamlined approval pathway for LPCN 1154, the results and timing of clinical trials, patient acceptance of Lipocine's products, the manufacturing and commercialization of Lipocine's products, and other risks detailed in Lipocine's filings with the SEC, including, without limitation, its Form 10-K and other reports on Forms 8-K and 10-Q, all of which can be obtained on the SEC website at . Lipocine assumes no obligation to update or revise publicly any forward-looking statements contained in this release, except as required by law. Company Codes: NASDAQ-SMALL:LPCN

In the driver’s seat on Alnylam’s cross-country road trip is Bernice Bennett, an author and genealogist. Mapped out along her route are stops to talk with a doctor who’s an expert on hATTR amyloidosis, as well as families that have been affected by the disease. A non-exhaustive list of supplies needed for a successful family road trip: a full tank of gas, plenty of snacks, a meticulously curated playlist and, according to Alnylam Pharmaceuticals, a thorough conversation about your family’s health history. The pharma has launched a new campaign, “Family Health History Road Trip,” to encourage people to have those conversations with their relatives, in hopes of identifying hereditary diseases they might be carrying as early as possible. The campaign is focused specifically on hereditary ATTR (hATTR) amyloidosis, a rare inherited condition in which a genetic variant leads to misfolded TTR proteins, which can then build up in the heart and other organs and tissues. Diagnosis of the rapidly progressing disease can take several years after symptoms begin, since those symptoms—which include a range of reactions from carpal tunnel syndrome to dizziness and shortness of breath to unintentional weight loss—overlap with those of many other, less-rare conditions. Currently, according to the American Heart Association, people with hATTR amyloidosis typically have a life expectancy of between 2.5 and 5 years after they’re diagnosed. One participant in Alnylam’s campaign said in a company release Wednesday that it took appointments with nine doctors over the course of seven years for her to finally receive a definitive diagnosis. “Once I mentioned my uncle’s history of amyloid neuropathy to my doctor, I was immediately offered a genetic test and finally received a diagnosis,” she said. “My symptoms were so different from my uncle’s that I never thought to discuss his health history with my doctor when I started my search for answers. If I had, I could have potentially been diagnosed and started on a disease management plan much earlier.” In the driver’s seat on Alnylam’s cross-country road trip is Bernice Bennett, an author and genealogist. Mapped out along her route are stops to talk with a doctor who’s an expert on hATTR amyloidosis, as well as families that have been affected by the disease. A highlight video from the trip shows Bennett going through family photo albums and chatting with patients’ family members about the process of uncovering the diagnosis behind what seemed like “a mystery illness.” She also meets with a doctor, who notes that “delay in diagnosis in a person is not only resulting in delay in diagnosis in them but also delay in diagnosis in the subsequent generations of their families.” “When we speak about family history, we often focus on the stories about what country we came from, where family immigrated to, or what types of jobs or professions they held; what we don’t often focus on is the health history of those who have walked before us,” Bennett says in the video. The highlight reel also gives a preview of Bennett’s route, starting in Chicago and winding through the Midwest before heading east for Massachusetts. And while the Family Health History Road Trip doesn’t overtly tout any branded treatments for the disease, the “treatment options” tab on the campaign’s accompanying website does redirect visitors to the site for Amvuttra, an RNAi drug from Alnylam that’s indicated to treat nerve damage in hATTR amyloidosis patients. The road trip-themed campaign is the latest in a string of hATTR amyloidosis programs that Alnylam has launched in recent years. Back in 2018, its “Bridge the Gap” campaign spotlighted a single extended family with cases of the disease spanning multiple generations, while another effort that launched last year focused on raising awareness of the rare disease in Europe via animated patient testimonial videos after Amvuttra was cleared on the continent. “Alnylam has been learning from the hATTR amyloidosis community for nearly two decades, and during that time, I’ve witnessed firsthand the devastating impact a delayed diagnosis can have on an individual’s quality of life and on their entire family,” Tiffany Patrick, VP of patient advocacy and engagement at Alnylam, said in this week’s announcement. “The Family Health History Road Trip program underscores Alnylam’s commitment to supporting improved health outcomes for the hATTR amyloidosis community.”

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced the launch of the Family Health History Road Trip , its program designed to encourage conversations between family members about their health history so they can discuss with their doctor to better understand their risk for developing an inherited disease like hereditary ATTR (hATTR) amyloidosis. Inspired by the traditional family road trip, the program follows genealogist and health educator Bernice Bennett as she embarks on a cross-country road trip to meet with a physician expert in hATTR amyloidosis and affected families to learn more about the disease, hear patients’ journeys to diagnosis and explore how knowledge of family health history can drive an earlier diagnosis. “When we speak about family history, we often focus on the stories about what country we came from, where family immigrated to, or what types of jobs or professions they held; what we don’t tend to focus on is the health history of those who have walked before us,” said Bennett. “Family history is considered one of the most important risk factors for health problems. Knowing your family’s health history empowers you with important information to share with your doctor when seeking a diagnosis or determining your risk for developing an inherited disease like hATTR amyloidosis.” hATTR amyloidosis is a rapidly progressive disease caused by an inherited variant, or change, in the transthyretin (TTR) gene, which causes the TTR protein to take on an abnormal shape, misfold and collect as amyloid deposits throughout the body, including the nerves, heart and digestive system, resulting in symptoms of the disease. Common symptoms may include carpal tunnel syndrome, tingling/numbness in the hands or feet, weakness, shortness of breath, diarrhea, constipation, dizziness and unintentional weight loss. These symptoms are similar to those of more common conditions and can vary widely among people with the condition, even within families, which may lead to misdiagnoses or delays in receiving an accurate diagnosis. In fact, patients may not receive a correct diagnosis until 3 to 6 years after symptom onset, resulting in significant disease progression and impacting entire families who remain unaware that there is an inherited disease in the family. “It took seeing nine doctors over seven years for me to finally receive a diagnosis of hATTR amyloidosis,” said Christine, a Family Health History Road Trip participant who is living with hATTR amyloidosis. “Once I mentioned my uncle’s history of amyloid neuropathy to my doctor, I was immediately offered a genetic test and finally received a diagnosis. My symptoms were so different from my uncle’s that I never thought to discuss his health history with my doctor when I started my search for answers. If I had, I could have potentially been diagnosed and started on a disease management plan much earlier.” With an inherited disease like hATTR amyloidosis that progresses rapidly, early diagnosis is crucial. When a diagnosis is delayed, appropriate management of the disease is also delayed, which is especially problematic as symptoms of hATTR amyloidosis can worsen over time and cause irreversible damage. That is why having health history conversations within families is so important – it equips current and future generations with important health information to share with their doctor and take action. A genetic test can determine whether a person carries one of the more than 120 variants in the TTR gene associated with hATTR amyloidosis. Once a gene variant is identified, family members of an affected individual can share this information with their doctor to help determine their own risk for the disease. “Alnylam has been learning from the hATTR amyloidosis community for nearly two decades, and during that time, I’ve witnessed firsthand the devastating impact a delayed diagnosis can have on an individual’s quality of life and on their entire family,” said Tiffany Patrick, MPH, MBA, Vice President, Patient Advocacy and Engagement at Alnylam Pharmaceuticals. “The Family Health History Road Trip program underscores Alnylam’s commitment to supporting improved health outcomes for the hATTR amyloidosis community.” hATTR amyloidosis is an autosomal dominant condition – meaning each child of one parent with hATTR amyloidosis has a 50 percent chance of inheriting the genetic variant that causes the condition. While a family member may inherit the TTR gene variant, having the variant does not necessarily mean that they will develop the disease. Although anyone can be at risk for developing hATTR amyloidosis, it is more common in certain ethnicities, such as people of African, Brazilian, French, Irish, Japanese, Portuguese and Swedish descent. To follow along on Alnylam’s Family Health History Road Trip and learn more about hATTR amyloidosis, the role of genetic testing, as well as ways you can start discussing family health history with loved ones, visit hATTRbridge.com/roadtrip . About Alnylam Pharmaceuticals Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO ® (patisiran), AMVUTTRA ® (vutrisiran), GIVLAARI ® (givosiran), OXLUMO ® (lumasiran), and Leqvio ® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P 5 x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam , or on LinkedIn , Facebook , or Instagram .